Enzyme Modulators

<p>Mirodenafil dihydrochloride is a potent phosphodiesterase-5 (PDE5) inhibitor, which is a synthetic compound with a primarily chemical origin. Its mode of action involves the inhibition of the enzyme PDE5, which predominantly resides in the smooth muscle cells lining blood vessels. By inhibiting PDE5, Mirodenafil dihydrochloride effectively increases the levels of cyclic guanosine monophosphate (cGMP), leading to the relaxation of smooth muscle tissues and vasodilation.</p>

<p>COX1 inhibitor; blocker of Ca2+-activated non-selective cation channels</p>

<p>Metformin is a widely used anti-hyperglycemic (anti-diabetic) agent for the treatment of type 2 diabetes mellitus. This is due to it decreasing blood glucose by decreasing hepatic glucose product by activation of the AMP-activated protein kinase AMPK. Studies have also demonstrated Metformin to have anti-cancer activity, attributed to several mechanisms such as inhibition of mammalian target of rapamycin (mTOR), cancer stem cells and inflammation.</p>

<p>Lenvatinib is an anti-cancer drug that is a multi-kinase inhibitor for VEGFR1, VEGFR2 and VEGFR. It has been shown to be effective against several cancers such as thyroid cancer and is currently in clinical trials for the treatment of leukaemia and prostate cancer. Furthermore, Lenvatinib also inhibits the activity of other protein kinases, including those involved in inflammatory responses.</p>

<p>Inhibitor of CSF1R receptor</p>

<p>Specific inhibitor of 8-oxoguanine glycosylase OGG1 with IC50 in submicromolar range. The compound inhibits binding of OGG1 to its substrate 8-oxoguanine, a guanine analog generated in the presence of reactive oxygen species (ROS). It was shown that TH5487 decreases inflammation level by inhibiting the base excision DNA repair in mice and altering the OGG1 chromatin dynamics. The compound also has implications in cancer biology since OGG1 inhibitors sensitise tumours to chemotherapy.</p>

<p>Inhibitor of HMG-CoA reductase</p>

<p>Gastric proton pump inhibitor</p>

<p>Neuronal selective nitric oxide synthase inhibitor</p>

<p>Farnesyl pyrophosphate synthase inhibitor; hepatic de novo lipogenesis inhibitor</p>

<p>Inhibitor of PIP5K1C</p>

<p>Irinotecan hydrochloride trihydrate is a topoisomerase I inhibitor that is used as chemotherapy drug for colorectal cancer. By inhibiting topoisomerase I, Irinotecan hydrochloride trihydrate prevents the replication of DNA in cells, and stops the cancer cells from growing and dividing. When used for chemotherapy, Irinotecan hydrochloride trihydrate is usually part of combination therapy with other chemotherapy drugs, such as 5-fluorouracil (5-FU) and leucovorin for other cancers.</p>

<p>Lenvatinib is a tyrosine kinase inhibitor that is used to treat cancers such as solid tumours. This drug inhibits the activity of VEGR receptors. It also inhibits other receptors such as fibroblast growth factor.</p>

<p>Tyrosine kinase inhibitor; antineoplastic activity; pro-apoptotic</p>

<p>Vorinostat is a histone deacetylase inhibitor which interferes with gene transcription regulatory mechanisms. It is used to treat cutaneous manifestations in patients with progressive, persistent, or recurrent cutaneous T- cell lymphoma (CTCL) following prior systemic therapies. This drug inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II).</p>

<p>Inhibitor of lipoprotein-associated phospholipase A2</p>

<p>Inhibitor of FLT3 receptor tyrosine kinases; anti-neoplastic</p>

<p>Glutamine analogue and antagonist of glutamine-dependent amidotransferases, with antibiotic and antifungal properties. Inhibits purine biosynthesis, FGAM synthetase and glucosamine-6-phosphate isomerase that contributes to its antineoplastic property. Azaserine can also act as a carcinogen, by inducing DNA carboxymethylation. Protects endothelial cells from inflammation under hyperglycemic conditions, via antioxidant mechanisms, independent of hexosamine biosynthetic pathway.</p>

<p>Inhibitor of O-GlcNAcase and N-acetylhexosaminidases</p>

<p>ATP competitive JAK2 inhibitor</p>

<p>Natural anti-cancer agent; inhibitor of histone deacetylases</p>

<p>Bortezomib is a selective and reversible inhibitor of the multicatalytic 26S proteasome. The inhibition of protein breakdown affects several metabolic pathways and leads to cell death. The compound is effective in treating t-cell lymphomas and multiple myeloma because it prevents the binding of myeloma cells to bone marrow stroma and inhibits osteoclast differentiation.</p>

<p>Indirubin is a chemical compound that belongs to the indole family. It has been studied for its anti-inflammatory and antipyretic properties. Research suggests that Indirubin can inhibit certain kinases displaying antineoplastic properties.</p>

<p>Inhibitor of GSK3 kinase; activator of Wnt signalling</p>

<p>Inhibitor of p38 MAPK kinase</p>

<p>Mitochondrial division inhibitor (mdivi-1) inhibits dynamin related protein-1 (drp1)-dependent mitochondrial fission. It is a therapeutic candidate for the treatment of stroke, myocardial infarction and neurodegenerative disease. The neuroprotective effects of mdivi-1 has been demonstrated in various models of brain ischemia and neurodegeneration.</p>

<p>Inhibitor of sodium/potassium ATP-ase; anti-arrhythmic</p>

<p>Gemcitabine is as a synthetic pyrimidine nucleoside prodrug. The hydrogen atoms on the 2' carbon of deoxycytidine are replaced by fluorine atoms. Gemcitabine works by being incorporated into the DNA of cancer cells during replication and inhibiting DNA synthesis. First gemcitabine is converted into its active form, gemcitabine triphosphate, by cellular enzymes including deoxycytidine kinase (DCK), after it is taken up by cancer cells. The gemcitabine triphosphate interferes with the normal functioning of the enzymes involved in replicating DNA, leading to the termination of DNA synthesis and ultimately, cell death. Gemcitabine is used as a chemotherapy drug used to treat various types of cancer, including pancreatic, lung, breast, and ovarian cancer.</p>

<p>Nicotinamide phosphoribosyl transferase (NAMPT) competitive inhibitor with IC50 = 3.1 nM. A major consequence of NAMPT inhibition is the attenuation of glycolysis at the GADPH step because this enzyme requires NAD+ for activity. The compound exhibits broad spectrum anti-cancer activity and significant tumor regression was observed in vitro. Although retinal and haematological toxicity has been associated with NAMPT inhibitors, LSN 3154567 does not lead to retinopathy in rats and can be mitigated with co-administration of nicotinic acid.</p>

<p>Imatinib is a tyrosine kinase inhibitor that is used in the treatment of various leukemias and gastrointestinal stromal tumors. This drug inhibits the BCR-ABL tyrosine kinase. It is suggested that Imatinib also inhibits other tyrosine kinases such as PDGF, SCF and c-Kit.</p>

<p>Inhibitor of histone deacetylase 3 (HDAC3) with IC50 in nanomolar range. BRD 9908 was shown to preserve the insulin-secreting pancreatic cells in nonobese diabetic mice. BRD 3308 supressed infiltration of mononuclear cells and prevented β-cell death in vivo as well as increased basal insulin secretion in vitro. Studies on HIV infection models showed that HDAC3 inhibition by BRD 3308 disrupts the HIV latency by increasing the gene expression from HIV promoter.</p>

<p>Rapamycin is a macrolide antibiotic that has been studied as a potential anticancer agent. It binds to FK506 binding proteins (FKBPs) to form a complex that inhibits mammalian targets of rapamycin (mTOR). Rapamycin also blocks p70 S6 kinase activation by interleukin-2 and thereby inhibits proliferation of T cells. It induces differentiation of human pluripotent stem cells (hPSCs) to mesendoderm and blood progenitor cells.</p>

<p>Selective, potent, competitive and reversible inhibitor of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) with IC50 of 2.3 nM and more than 10000-fold selectivity over the related 11β-HSD-2 isoform. BMS 823778 inhibits conversion of cortisone in cortisol and has applications in the treatment of diabetes type 2 since it can influence the occurrence of insulin resistance.</p>

<p>Irreversible blocker of three members of the ErbB family (ErbB1, ErbB2/HER2, and ErbB4) with IC50 in nanomolar range. The compound binds covalently to cysteine 797 residue in HER2 and blocks downstream cellular signalling, inhibits cellular growth and promotes apoptosis. Afatinib has been used for the treatment of tyrosine kinase inhibitor-resistant tumours with mutations in ErbB genes, especially for deletions in exon 19 and single nucleotide substitutions in exon 21. It has been used for treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, colorectal cancer, etc.</p>

<p>Inhibits Mer receptor tyrosine kinase (IC50 = 4.3 nM). Selective over Axl (84-fold) and Tyro3 (58-fold). UNC 2881 inhibits phosphorylation of Mer kinase in 697 B-ALL cells (IC50 = 22nM). Inhibits EGF-induced activation of a chimeric enzyme, composed of EGFR fused with Mer. Blocks collagen-mediated platelet aggregation, implying the potential of this compound for treating thrombosis.</p>

<p>Selective inhibitor of the mutated RET variant RETV804M, which is the anticipated drug-resistant RET mutant that can occur in tumours treated with kinase inhibitors. The compound has a biochemical IC50 of 0.02 µM and selectivity for purified RETV804M over purified RET and KDR of 3.7 and 110, respectively. The efficacy of the compound was shown also in cell cultures with IC50 of 4.4 µM, and cell assay selectivity for RETV804M over RET and KDR of 0.89 and 2.3, respectively.</p>

<p>Inhibitor of VEGF receptor tyrosine kinases and non-receptor tyrosine kinases</p>

<p>Zorubicin hydrochloride is an anthracycline antibiotic, which is a derivative of daunorubicin, sourced from Streptomyces bacteria. This compound exhibits its mode of action primarily through intercalation into DNA, inhibiting the progression of the enzyme topoisomerase II. This interference prevents DNA replication and RNA synthesis, leading to apoptosis in rapidly dividing cells, making it a potent chemotherapeutic agent.</p>

<p>Cerivastatin is a drug that belongs to the class of drugs called statins. This drug is used to reduce the risk of cardiovascular events and lower lipid levels. Cerivastatin is an HMG-CoA reductase inhibitor and allows for a decrease in cholesterol in hepatic cells. Cerivastatin is cardioprotective and anti-atherosclerotic.</p>

<p>Protein kinase B (also known as RAC-alpha serine/threonine-protein kinase: Atk) is a serum and glucocorticoid-regulated protein kinase with three highly homologous isoforms (Akt1, 2 and 3). Akt1 and Akt3 are the predominant isoforms expressed in the brain, whereas Akt2 is mainly expressed in skeletal muscle and embryonic brown fat. These proteins play major regulatory roles in a range of physiological processes including: growth, proliferation, cell survival, angiogenesis, metabolism and Akt is also considered a proto-oncogene.This peptide (AKTide) is a selective substrate for these kinases and enables quick, easy and sensitive assays of Akt activity.</p>

<p>The sequence of this peptide has been derived from a highly conserved region of the T-cell phosphatase TC.PTP45 and is an excellent general substrate for protein tyrosine phosphatases.The protein tyrosine phosphatase (PTP) superfamily has 103 enzymes that catalyse substrate dephosphorylation at tyrosine residues through a covalent enzyme intermediate involving a thiophosphate linkage from the active site cysteine residue. All PTPs share a common signature motif (I/V)HCXAGXGR(S/T), named the P-loop, responsible for the enzyme activity. The PTP superfamily can be divided into four classes based on their cellular localization/catalytic domains: the receptor-like PTPs (rPTPs), the non-receptor PTPs (nrPTPs), the low molecular weight PTP (LMWPTP), and the VH-1 and CDC-25 groups.PTPs are involved in regulating a plethora of cellular activities, including proliferation and differentiation, survival, migration, metabolism, and the immune response. Abnormal protein tyrosine phosphorylation has been associated with the etiology of various human diseases, including cancer, diabetes, and autoimmune dysfunctions, therefore making PTPs novel therapeutic targets.</p>

<p>Cyclin-dependent kinases (CDKs) are a family of kinases that regulate the cell cycle and gene transcription. Cyclin-dependent kinase 7 (CDK7) forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK) and promotes cell cycle progression. CDK7 is an essential component of the transcription factor TFIIH, involved in DNA repair. CDK7 is also implicated in mRNA processing, transcription activation, pause induction, and pause release.CDK8 associates with the mediator complex and regulates transcription via several mechanisms, including influencing binding of RNA polymerase II to the mediator complex. CDK8 phosphorylates the Notch intracellular domain, SREBP, and STAT1. Its regulatory subunit is cyclin C. CDK9 is a component of the TAK/P-TEFb complex, which phosphorylates the part of RNA polymerase II. Its regulatory subunit is cyclin T or cyclin K. CDK9 interacts with HIV-1 Tat protein and TRAF2, and is involved in the differentiation of skeletal muscle.CDKs are often over expressed in cancers and may correlate with poor prognosis. This peptide is based on the C-terminal of RNA polymerase II and is used in kinase assays.</p>

<p>Ile-Pro-Pro (IPP) has the ability to inhibit angiotensin-converting enzyme and stimulate the production of nitric oxide. It could be used to improve hypertension thus reducing the risk of cardiovascular diseases.</p>

<p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is negative regulator of hepatic low-density lipoprotein (LDL) receptors by promoting their degradation. This leads to an increase in plasma levels of cholesterol-LDL (LDL-c). PCSK9 binds to the LDL receptor at the epidermal growth factor precursor homology domain A (EGF-A) which leads the receptor to be targeted for degradation. Natural loss of function mutations in PCSK9 have been linked to improved coronary health and lower cholesterol levels with reduced risk of coronary heart disease. This has led to further study to find inhibitors of PCSK9 with the hope that they may be clinically relevant in the future.As discussed, PCSK9 binds to EGF-A on the LDL receptor. A peptide named pep 2-8 is a mimic of EGF-A and binds PCSK9 in the same manner observed with the LDL receptor. Pep 2-8 is a potent selective competitive inhibitor of PCSK9. Pep 2-8 restores LDL receptor function and LDL uptake of PCSK9-treated HepG2 cells. This is still an active area of research to optimise inhibition of PCSK9 for cholesterol regulation.Pep 2-8 has also been utilised as an anchor peptide in phage-display experiments to bind an extension peptide library to the groove site.Peptide Ac-TVFTSWEEYLDWV-NH2 is a Research Peptide with significant interest within the field academic and medical research. This peptide is available for purchase at Cymit Quimica in multiple sizes and with a specification of your choice.</p>

<p>Abltide represents the optimal substrate peptide of Abl (or c-Abl), a non-receptor tyrosine kinase (NRTK) and the oncogenic Bcr-Abl tyrosine kinase (TK) (formed via a fusion between the Abelson (Abl) TK gene and the break point cluster region protein Brc). Abl was discovered as the gene from which the Abelson leukaemia virus derived its Gag-v-Abl oncogene.TKs are critical enzymes involved in multiple signalling pathways. However, Tks can promote cancer progression when deregulated, for example deregulated TK, Bcr-Abl gives rise to chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukaemia (Ph+ ALL).Abl is activated by various signals including: growth factors, cytokines, cell adhesion, DNA damage and oxidative stress and results in the stimulation of both pro- and anti-apoptotic roles, cell proliferation or differentiation, retraction, or migration. Abl phosphorylates a large number of functionally diverse substrates, in part due to its ability to shuttle between the cytosol and the nucleus and bind both DNA and actin&amp;mdash-two biopolymers with fundamental roles in almost all biological processes.</p>

<p>H-FERQHM-OH peptide, corresponding to RNase A 8-13 (Chain A of bovine pancreatic ribonuclease) is a non-amyloidogenic peptide, that can be used as a negative control in amyloid formation experiments together with CRB1001320.</p>

<p>eV1-2 is a selective εPKC inhibitor peptide which interferes with protein-protein interactions between the ϵPKC isozyme and its anchoring protein (ϵRACK). ϵPKC and ϵRACK regulate the contraction rate of heart muscle cells and provide protection from ischemia induced cell death. ϵV1-2 is derived from the C2 domain of ϵPKC, a region important for protein-protein interactions and thus acts as a competitive inhibitor of these interactions. The C2 region is well conserved between species, but different enough from other PKC isozymes to allow for targeted inhibition (ϵV1-2 is 88% identical between sea slugs and rat ϵPKC, yet only 36% identical between rat ϵPKC and rat θ´PKC). This peptide contains a C-terminal cysteine residue for conjugation to a carrier protein.</p>

<p>Acid α-glucosidase (83-99) (human) is derived from the exogenous enzyme which degrades glycogen, maltose and isomaltose through targeting alpha -1,4 and alpha -1,6 linkages. Once synthesised in its precursor form, within the Golgi it is glycosylated and acquires mannose 6-phosphate residues. This allows it to be transported to the Lysosome in a multistep process.Pompe disease, also known as glycogen storage disease type II, can be diagnosed through the absence of acid α-glucosidase activity within patients. Therefore glycogen degradation in the lysosome is inhibited by this autosomal recessive disorder. This results in the accumulation of glycogen and tissue destruction, hence contributing to the pathologies of muscle weakness and respiratory failure, associated with infantile onset and adult onset Pompe disease.</p>

<p>ERKtide Substrate Peptide.</p>

<p>This peptide is phosphorylated by Janus kinase 2 (JAK2) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-33 predominantly contained 3 peptides - KLSDW, YPSPV, and MPVHTDAD). YPSPV in EYGF-33 was found to have minimal antioxidant activity. However, YPSPV showed notably high angiotensin converting enzyme (ACE) inhibitory activity, it exceeded the positive control captopril.</p>

<p>A15 also known as alpha2-Antiplasmin is a serine/protease inhibitor which inactivates plasmin in the blood. To inhibit plasmin in the blood alpha2-Antiplasmin forms a protease serpin complex with plasmin due to interactions of kringle 1 or 3 of plasmin and the lysine residues of alpha2-Antiplasmin's C-terminus. Although synthesised in the Liver A15 is also present within the neurons of the human brain and its expression has been found to be enhanced in Aβ plaques of Alzheimer's disease and during myocardial infarction. A high concentration of alpha2-Antiplasmin in the blood may also contribute to an increased risk of Ischemic strokes. Alternatively its expression appears to be diminished in patients with cirrhosis and acute liver failure. A further function of A15 is its ability to regulate fibrinolysis through crosslinking to fibrin.</p>

<p>DARKtide is a substrate peptide for death-associated protein kinase (DAPK) for use in kinases assays. DAPK is involved in several cellular pathways including: apoptosis, tumour suppression, stress response, anti-viral immunity and IL-1-associated inflammatory diseases. In C. elegans DAPK-1 regulates epidermal morphogenesis, innate immunity and wound repair.</p>

<p>Amino acids 651-660 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates the relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>Axltide-is a substrate peptide for use in kinase assays and is based on the mouse insulin receptor substrate 1 (IRS1) (amino acid 979-989).IRS1 is a membrane-proximal adaptor protein, which binds to, and is phosphorylated by, the insulin receptor (IR) at its tyrosine residue. IRS1 transmits the extracellular signal for insulin to serine/threonine kinases, such as Akt which then deliver the signal into the cell to mediate the various actions of insulin.</p>

<p>Substrate for proline-rich tyrosine kinase 2 (Pyk2)- can be used for substrate phosphorylation assays. Pyk2 is a member of the focal adhesion kinase (FAK) subfamily of cytoplasmic tyrosine kinases. Pyk2 is also known as: calcium-dependent tyrosine kinase (CADTK)- cellular adhesion kinase β- related adhesion focal tyrosine kinase (RAFTK)- or FAK2.Pyk2 functions as a scaffold protein, and it interacts with cytoplasmic proteins at focal adhesion sites to integrate different environmental signals. Pyk2 is activated by several stimuli, including elevated intracellular calcium levels, protein kinase C activation, and exposure to stress factors. Recently, Pyk2 has become a potentially important new therapeutic target or prognostic marker because overexpression of Pyk2 has been found in many human tumours.</p>

<p>ERKtide Substrate Peptide.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-56 predominantly contained 3 peptides - SDNRNQGY, KGLWE, and IQVPL. KGLWE in EYGF-56 was found to have very strong antioxidant activity. KGLWE showed minimal angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-56 predominantly contained 3 peptides - SDNRNQGY, IQVPL, and KGLWE. IQVPL in EYGF-56 was found to have minimal antioxidant activity. YPSPV showed some angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>The peptide IRW, characterised from egg protein, exhibits inhibitory properties against the angiotensin converting enzyme (ACE2) and could be used to prevent cardiovascular disease with further research. Treatment of hypertensive mice with IRW induced endothelium-dependent vasorelaxation and reduced vascular inflammation. The IRW tripeptide acts as anti-hypertensive by upregulating ACE2 activity via the Mas receptor (MasR) and upregulating Akt/eNOS signalling in the aorta. IRW also induces superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. These may play a factor in IRW's role as an anti-inflammatory. IRW shows promise as a nutraceutical for inflammatory conditions and a tool for drug development in cardiovascular disease.</p>

<p>Peptide derived from the endothelial nitric oxide synthase which synthesises nitric oxide in order to protect endothelial cells from vascular diseases, atherosclerosis and thrombosis.</p>

<p>Human epidermal growth factor receptor 2 (HER-2)/epidermal growth factor receptor-2 (ErbB-2), is a key receptor linked to metastasis in tumours. The oncogenic ErbB-2 receptor has intrinsic receptor tyrosine kinase (RTK) activity. The receptor is activated by ligand binding which induces receptor dimerization. These RTK complexes can activate mitogen-activated protein kinase (MAPK) and phosphoinositol 3'-kinase (PI3K)/Akt pathways. This peptide has been identified as a substrate for HER-2/ErbB-2 as it is phosphorylated upon receptor activation and therefore acts as a marker for receptor activation in kinases assays.</p>

<p>This peptide is phosphorylated by Janus kinase 1 (JAK1) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.This JAK1 substrate peptide contains an N-terminal Glycine-residue and a phospho-tyrosine-residue.</p>

<p>Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and its negative regulator Kelch-Like ECH-Associated Protein 1 (Keap1) provide vital protection in maintaining cellular redox. In parallel, Nrf2 also aids the resolution of inflammation and also tissue repair. In homeostatic conditions, the transcription factor Nrf2 is controlled in a cytoplasmic complex with Keap1 with ubiquitination and protein degradation. Nrf2 has been linked to numerous cancers due to mutations affecting the binding region of Nrf2 to Keap1, resulting in Nrf2 dissociating from the complex. Nrf2 constitutively accumulates in the nucleus and activation of prosurvival genes that promote cancer cell proliferation.The Neh2 region of Nrf2 interacts with Keap1, as shown by nuclear magnetic resonance spectroscopy. The 16 amino acid peptide (AFFAQLQLDEETGEFL) (69-84) flanks the conserved ETGE motif and can replicate the binding to keap1.Therapeutics targeting the Nrf2 signalling pathway and activation of Nrf2 is a keen area of research, with many cancers being linked to Nrf2, particularly pancreatic cancer. Additionally, activation of Nrf2 has become a possible target as a treatment for COVID. Nrf2 (69-84) replicating full-length Nrf2 binding has been helpful in all cases.</p>

<p>A glycogen synthase kinase 3β- (GSK3β-) / crosstide fragment representing the phosphorylation site on GSK3β-. GSK3β- is a serine/threonine kinase which regulates glycogen synthase activity and is a key mediator of vertebrate development, tumourigenesis and cell differentiation. GSK3β- is phosphorylated by activated AKT/protein kinase B on serine 9- promoting its inactivation.</p>

<p>Amino acids 487-496 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>LRRKtide (also called moesin) is a peptide substrate for leucine-rich repeat kinase 2 (LRRK2). The sequence of LRRKtide has been derived from the ERM proteins: Ezrin (amino acids 561-573), radixin (amino acids 558-570) and moesin (amino acids 539-553). These proteins influence cytoskeletal dynamics by anchoring the cytoskeleton to the plasma membrane. LRRK2 phosphorylates LRRKtide at its Thr558 site. This peptide contains the phosphorylated threonine residue.LRRK2 is a large, ubiquitous protein of unknown function. LRRK2 has GTPase and kinase activity, and is located in multiple areas of the cell, associated with intracellular membranes and vesicular structures- suggesting LRRK2 may be involved in several cellular pathways. LRRK2 is also found in most organs and mutations in LRRK2 have been identified in Parkinson's disease.The threonine residue at position 9 of this peptide has been phosphorylated.</p>

<p>A protein kinase G selective substrate for use in kinases assays, with a preference for PKG Ialpha over PKG II. PKG is a serine/threonine-specific protein kinase activated by cyclin guanosine monophosphate (cGMP). PKG is involved in several signalling pathways including: smooth muscle relaxation, platelet function, cell division, nucleic acid synthesis and sperm metabolism.</p>

<p>Substrate peptide for protein tyrosine phosphatase 1B (PTP1B)- an ubiquitously expressed non-receptor tyrosine phosphatase. PTP1B negatively regulates signalling pathways controlling metabolic homeostasis, cell proliferation and immunity (such as leptin and insulin receptor signalling), making PTP1B an interesting target for type 2 diabetes mellitus (T2DM) and obesity treatment. PTP1B also has important leptin-independent metabolic effects, playing a critical role in the regulation of inflammation, cell proliferation, differentiation and invasion. Therefore PTP1B is also interesting as a therapeutic target for inflammatory and autoimmune diseases and cancer.-For application data please see: Figure 2 supplement 1C.</p>

<p>Autocamtide-2-related inhibitory peptide is a calmodulin-dependent protein kinase II (CaMKII) inhibitor.CAMK represents a class of Ca2+/calmodulin-dependent protein kinase enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and transfers phosphates from ATP to defined serine or threonine residues in other proteins. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes.</p>

<p>Amino acids 359-409 of human glycogen synthase kinase 3 β (GSKβ), a multifunctional serine/threonine kinase widely expressed in most mammalian cells. GSKβ is highly active under basal conditions and acts downstream of phosphoinositide 3-kinase (PI3K) signalling. PI3K activation results in Akt phosphorylation and the subsequent phosphorylation of GSKβ at serine-9 and its inactivation. GSKβ in turn activates the production of pro-inflammatory cytokines including IL-1β, IL-6, IL-12, IL-17, TNFalpha and IFNγ, and supresses the production of IL-10, IL-1Ra, and IFNβ by immune cells. Under resting conditions, GSKβ is constitutively active due to tyrosine-216 phosphorylation, and it phosphorylates and inhibits a diverse group of pro-oncogenic substrates, such as: β-catenin- cyclin D1- c-Jun- c-Myc and CREB. GSKβ is also involved in Wnt signalling pathways.Aberrant expression of GSKβ has been shown to promote cell growth in some cancers and to suppress it in others. GSKβ inhibition leads to the accumulation of β-catenin in the nucleus, enhancing the progression of many cancers. However the inhibition of GSKβ also induces apoptosis in various types of cancers, such as pancreatic, colorectal and bladder cancer. Inhibition of GSKβ can also have neuroprotective effects on dopaminergic neurons such as in Parkinson's disease.</p>

<p>Phosphorylated EGFR peptide substrate.</p>

<p>Amino acids 487-496 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>Cell permeable peptide which is able to activate phosphoinositide 3- kinase, for which it binds with high affinity to the p85 subunit. 740 Y-P also has mitogenic activity as it is able to induce mitosis in muscle cells, and promotes cell survival in neurones. PI 3- kinase's are a family of enzymes involved in many cellular pathways including cell proliferation, growth, differentiation, survival, motility, and intracellular trafficking. PI 3 Kinases are therefore also involved in many cancers.</p>

<p>LRRKtide (also called moesin) is a peptide substrate for leucine-rich repeat kinase 2 (LRRK2). The sequence of LRRKtide has been derived from the ERM proteins: Ezrin (amino acids 561-573), radixin (amino acids 558-570) and moesin (amino acids 539-553). These proteins influence cytoskeletal dynamics by anchoring the cytoskeleton to the plasma membrane. LRRK2 phosphorylates LRRKtide at its Thr558 site.LRRK2 is a large, ubiquitous protein of unknown function. LRRK2 has GTPase and kinase activity, and is located in multiple areas of the cell where it is found associated with intracellular membranes and vesicular structures. Its multiple cellular locations suggest that LRRK2 may be involved in several cellular pathways. LRRK2 is also found in most organs and mutations in LRRK2 have been identified in Parkinson's disease.This peptides has an amidated C-terminal end.</p>

<p>AMARA peptide is a fragment containing the phosphorylation site for AMP activated protein kinase (AMPK) and is a substrate for all AMPK subfamily kinases. As such it is used to measure AMPK related kinase activity.</p>

<p>MGMT, known as O6-methylguanine-DNA methyltransferase, is a DNA repair enzyme that plays an important role in chemoresistance to alkylating agents. MGMT repairs the toxic DNA O6-Methylguanine lesion caused by Temozolomide (TMZ), an oral alkylating agent used for the treatment of glioblastoma. MGMT repairs damaged guanine nucleotides by transferring the methyl at O6 site of guanine to its cysteine residues, thus avoiding gene mutation, cell death and tumorigenesis. The expression of MGMT gene is mainly regulated by epigenetic modification. Loss of MGMT expression is due to methylation of the CpG island of MGMT promoter.</p>

<p>This peptide is phosphorylated by Janus kinase 1 (JAK1) and is an ideal substrate for use in kinase assays. The JAK family of kinases is essential for the signalling of a host of immune modulators in tumour, stromal, and immune cells where they are highly expressed. JAK family proteins mediate the signalling of the interferon (IFN), IL-6, and IL-2 families of cytokines.JAK kinases are associated with cytokine receptors. Cytokine binding to these receptors results in activation of JAK kinases and receptor phosphorylation. Phosphorylated cytokine receptors recruit STAT proteins, which are then phosphorylated by the activated JAK kinases. Phosphorylated STAT proteins form homo- and hetero-dimers that translocate into the nucleus and function as transcription factors.This JAK1 substrate peptide contains an N-terminal glycine-residue.</p>

<p>During extraction of lecithin from egg yolk, peptide by-products can be isolated and purified by gel filtration. Within the by-products this has led to the discovery of biologically active value-added products. The egg yolk gel filtration (EFGF) fractions were analysed for their antioxidant and angiotensin converting enzyme (ACE) inhibitory activities. EYGF-33 predominantly contained 3 peptides - KLSDW, YPSPV, and MPVHTDAD). KLSDW in EYGF-33 was found to have strong antioxidant activity linked to the presence of the tryptophan residue. KLSDW had nearly comparable activity to the synthetic antioxidant BHA. KLSDW did not show any notable angiotensin converting enzyme (ACE) inhibitory activity.</p>

<p>Autocamtide-3-related inhibitory peptide is a calmodulin-dependent protein kinase II (CaMKII) inhibitor. AC3-I is derived from Autocamtide-3, a substrate for CaMKII, with the Thr-9 phosphorylation site substituted with Ala.CAMK represents a class of Ca2+/calmodulin-dependent protein kinase enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and transfers phosphates from ATP to defined serine or threonine residues in other proteins. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes.</p>

<p>HMG-CoA reductase inhibitor; anti-hypercholesterolemia agent</p>

<p>Orlistat is a drug that has been approved for the treatment of obesity. It inhibits gastric and pancreatic lipases, which are enzymes that break down dietary fats into smaller molecules to facilitate absorption. Orlistat has been shown to reduce coronary heart disease in patients with type 2 diabetes. Orlistat has also been shown to have a significant upregulation of gene expression associated with disease activity when injected into the skin of patients with primary pulmonary hypertension.<br>Orlistat is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™  products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>Etoricoxib is a cyclooxygenase-2 (COX-2) inhibitor, which is a type of nonsteroidal anti-inflammatory drug (NSAID). It works by blocking the enzyme COX-2 that is involved in the production of certain hormones called prostaglandins. These hormones are involved in the inflammation (swelling and heat) associated with conditions such as arthritis. By blocking the action of the COX-2 enzyme, Etoricoxib reduces the production of prostaglandins and thus, reduces the inflammation and pain. <br>Etoricoxib is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>Cyclosporin A (CsA) is a cyclic undecapeptide that is extracted from the fungus Tolypocladium inflatum. CsA is used as an immunosuppressive drug to prevent rejection of transplanted organs and to treat autoimmune diseases such as rheumatoid arthritis and psoriasis. CsA works by binding to a protein called cyclophilin D, which is a component of the enzyme calcineurin. Calcineurin is an important enzyme involved in the activation of immune cells, and by binding to cyclophilin D, CsA inhibits its activity. This leads to the inhibition of T-cell activation and the suppression of the immune response. Cyclosporin A has has been rpeorted to exhibit some nephrotoxicity, hypertension and also increases the risk of infections and tumors when used in transplantation</p>

<p>novel tricyclic indole; promising new treatment for a variety of diseases</p>

<p>Aurora kinase inhibitor; antineoplastic</p>

<p>Pentoxifylline is a methylxanthine derivative that is used to treat intermittent claudication that is caused by chronic occlusive arterial disease of the limbs. This drug also has antioxidant and anti-inflammatory properties. Pentoxifylline is a phosphodiesterase inhibitor aiding to increase levels of cAMP.</p>

<p>Inhibitor of S-adenosylhomocysteine hydrolase that disrupts histone methylation by EZH2. Anti-proliferative in some breast cancer and invasive prostate cancer cell lines. One of four key molecules required for inducing chemical reprogramming of somatic cells into induced pluripotent stem cells (iPSC).</p>

<p>Ozagrel is an antiplatelet agent that is also a thromboxane A2 synthetase inhibitor. It is used for the treatment of bronchial asthma and cerebral ischemia. It blocks platelet aggregation and reduces hypersensitivity of bronchial muscles.</p>

<p>Doxorubicin hydrochloride is an inhibitor of topoisomerase II with anti-neoplastic activity and belongs to the class of anthracyclines. It is cytotoxic, and interferes with the topoisomerase II-mediated repair of DNA causing accumulation of mutations. Doxorubicin also leads to the generation of reactive oxygen species (ROS), which further damages DNA as well as proteins and membranes. Doxorubicin is used as a chemotherapy treatment for various types of cancer, including breast cancer, lung cancer, ovarian cancer, and leukaemia. However, the compound presents with a risk of developing cardiomyopathy as well as drug resistance.</p>

<p>Zoledronic acid is a drug that is used for the treatment of malignancy associated with hypercalcemia and bone metastasis from tumors. This drug induces apoptosis pf hematopoietic tumor cells by inhibiting farnesyl diphosphate. Zoledronic acid is a bisphosphate that inhibits osteoclast function and bone resorption.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>This product is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>