Organometallic Ligands

<p>Nilutamide is an antineoplastic agent that is used to treat prostate cancer. This drug is an androgen receptor antagonist and binds with androgen receptors thus blocking its action and resulting in growth arrest.</p>

<p>Soyasaponin II is a naturally occurring triterpenoid saponin that is primarily extracted from soybeans, a rich source of biologically active phytochemicals. Its mode of action involves the modulation of cellular pathways and the alteration of membrane dynamics, which can affect various signaling cascades. This compound is particularly noted for its potential anti-inflammatory, antioxidant, and anticancer properties, making it a subject of extensive research in pharmacological contexts.</p>

<p>Fluvastatin is a statin that lowers blood cholesterol and triglycerides by inhibiting HMG-CoA reductase, an enzyme that plays a critical role in the synthesis of cholesterol. Fluvastatin has also been shown to reduce the incidence of myocardial infarction, and to reduce atherosclerotic lesions in animal models, reducing the incidence of cardiovascular disease. Fluvastatin also has been shown to inhibit the activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), which may be related to its anti-inflammatory effects. Furthermore, through lowering blood cholesterol, Fluvastatin also inhibits tubulointerstitial injury and prevents renal damage caused by high concentrations of the lipid.</p>

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

<p>Apixaban is an anticoagulant agent used for the prophylaxis of stroke and deep vein thrombosis leading to pulmonary embolism. This drug is an inhibitor of factor Xa and prothrominase. As a result, this prevents the formation of a thrombus.</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>Rosuvastatin is a drug that belongs to the group of statins. It is used for the treatment of high cholesterol and as an adjunct therapy for patients with coronary heart disease. Rosuvastatin reduces serum cholesterol by inhibiting HMG-CoA reductase, which is the rate-limiting enzyme in the production of cholesterol. Furthermore, this drug has been shown to have anti-inflammatory properties, which may be due to its ability to inhibit prostaglandin synthesis.</p>

<p>GC 376 is an inhibitor of the main protease Mpro (3CLpro) in coronaviruses as well as picornaviruses. This broad-spectrum antiviral compound has been used as investigational veterinary drug for treatment of feline infectious peritonitis virus (FIPV) infections. Recent studies also showed that GC 376 inhibits the main protease Mpro (3CLpro) from SARS-CoV-2 with IC50 of 0.03 μM and EC50 of 3.37 μM.</p>

<p>Required for blood coagulation</p>

<p>Polmacoxib is a non-steroidal anti-inflammatory drug (NSAID), which is derived through synthetic chemical processes. It functions as a selective cyclooxygenase-2 (COX-2) inhibitor. By selectively inhibiting the COX-2 enzyme, polmacoxib reduces the conversion of arachidonic acid to prostaglandins that mediate inflammation and pain, while sparing the COX-1 enzyme that protects gastric mucosa and maintains platelet function.</p>

<p>Kifunensine is a small molecule inhibitor that was designed and synthesized to inhibit plant and animal α-mannosidase I. It is a potent and specific inhibitor with IC50 in nanomolar range. It inhibits the enzyme isoforms in Golgi apparatus (GMI) and endoplasmatic reticulum (ERMI). The compound prevents mannose trimming on glycoproteins and shifts the glycoform content from complex to oligomannose type. Used for the production of recombinant therapeutic glycoproteins with mannose rich N-linked glycans.</p>

<p>Tricyclic antidepressant</p>

<p>Histone acetyltransferase inhibitor of p300/CBP; anti-proliferative</p>

<p>6-O-Feruloylglucose is a bioactive compound, which is a glycosylated derivative of ferulic acid. It is derived from plant sources, particularly being prevalent in the cell walls of cereals and other plant materials. The compound's mode of action is associated with its ability to act as an antioxidant, neutralizing free radicals by donating hydrogen atoms or quenching reactive oxygen species. This makes it a significant molecule in the potential prevention of oxidative stress-related conditions.</p>

<p>Hydroxyl radical scavenger; anti-vasospastic</p>

<p>Inhibitor of BET bromodomain</p>

<p>TAS 6417 hydrochloride is a small-molecule inhibitor, which is synthesized via chemical processes in pharmaceutical research. It functions primarily as a potent and selective inhibitor of specific mutant forms of the epidermal growth factor receptor (EGFR). By targeting these EGFR mutations, TAS 6417 hydrochloride disrupts the signaling pathways that are crucial for the proliferation and survival of cancer cells.</p>

<p>Fibroblast growth factor receptor inhibitor</p>

<p>As a synthetic trifluorinated glucocorticoid receptor agonist, Fluticasone exhibits anti-inflammatory properties. When binding to and activating glucocorticoid receptors, Fluticasone initiates the activation of lipocortin which inhibits cytosolic phospholipase A2. Consequently, the cascade of inflammatory mediator synthesis reactions are inactivated and the production of inflammatory cells namely mast cells, dendritic cells, macrophages and eosinophils and the cytokines that they produce are greatly reduced.It is this anti-inflammatory role which has enabled Fluticasone to successfully treat conditions such as asthma, emphysema, allergic rhinitis and atopic dermatitis. It has also been seen to increase anti-inflammatory effects of annexoin-1 and mitogen-activated kinase phosphatase-1; reduce mucus gland secretions and increase the number of beta-2 receptors on smooth muscles of the airways.<br>Fluticasone 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>Inhibitor of HIF-prolyl hydroxylase isozymes PHD1, PHD2 and PHD3 with Ki in nanomolar range. The compound mimics the binding of N-oxalylglycine, chelates catalytic iron and prevents substrate entry into catalytic site. Inhibition of PHD enzymes leads to stabilization of hypoxia-induced factors HIF1α and HIF2α, followed by the production of erythropoietin (EPO).</p>

<p>Verapamil is drug that belongs to the class of drugs known as calcium channel blockers. It is used to treat high blood pressure, angina and other cardiovascular disorders. It works by relaxing the blood vessels so that blood can flow more easily. It does this by inhibiting the calcium ion influx through slow channels into conductile, contractile myocardial cells and vascular smooth muscle cells.</p>

<p>Ibandronate is a bisphosphate used in the treatment of osteoporosis in postmenopausal women. This drug slows down the activity of osteoclasts resulting in a slower process of bone breakdown. This drug also inhibits farnesyl diphosphate and induces apoptosis of hematopoietic tumor cells.</p>

<p>Bestatin is a competitive protease inhibitor. It inhibits aminopeptidase N and is being studied for the use and treatment for acute myelocytic leukemia.</p>

<p>Ticlopidine is a platelet aggregation inhibitor that is used in the prevention of conditions associated with thrombi such as stroke and ischemic attacks. This drug blocks the ADP receptor that is involved in GPIIb/IIIa receptor activation leading to platelet aggregation. By reducing platelet aggregation, ticlopidine helps prevent the formation of harmful blood clots that could block blood flow in arteries.</p>

<p>Sarpogrelate is a serotonin antagonist drug that is used for the treatment of various diseases such as diabetes, coronary artery disease and atherosclerosis. This drug inhibits serotonin-induced platelet aggregation.</p>

<p>A selective VHL inhibitor that stabilizes the hydroxylated form of HIF-α, resulting in upregulation of downstream target genes and proteins. Provides a tool for studying hypoxic signaling pathway.</p>

<p>Benserazide is a drug that is used for the treatment of Parkinson’s disease and restless leg syndrome. This drug is a decarboxylase inhibitor and is usually used in combination with Levodopa.</p>

<p>Lercanidipine is a calcium channel blocker that is used for the treatment of hypertension. This drug inhibits ion channels and interferes with the release of calcium from the sarcoplasmic reticulum. As a result, coronary and systemic arteries are dilated, allowing for an increased supply of oxygen to myocardial tissue. .</p>

<p>Flunarizine is calcium channel blocker that helps to reduce muscle spasms. It shows antimigraine and anticonvulsive activity. This occurs by inhibiting the influx of extracellular calcium through myocardial and vascular membrane pores by physically inhibiting the voltage-dependent calcium channels. Additionally, this drug is a D2 dopamine receptor antagonist.</p>

<p>Dutasteride is an androgenic compound and a 5α-reductase inhibitor that is used to treat benign prostatic hyperplasia (BPH) and male pattern baldness. Dutasteride reduces prostate volume and improves symptoms of BPH by inhibiting the enzyme 5α-reductase, which converts testosterone to dihydrotestosterone.</p>

<p>Dapoxetine is a serotonin reuptake inhibitor drug that is used to treat premature ejaculation. This drug works by increasing the levels of serotonin in the brain, which in turn can help to delay the reflex that triggers ejaculation. As a result, it delays ejaculation and improves control over this.</p>

<p>Tizanidine is an alpha-2 adrenergic agonist drug that is used in the treatment of muscle spasticity. This drug binds to alpha-2 adrenergic receptors and causes presynaptic inhibition of motor neurons. Additionally, it leads to a reduction in the release of amino acids such as glutamate and aspartate which have an excitatory effect.</p>

<p>Diclofenac is a non-steroidal anti-inflammatory drug that is used to treat the signs and symptoms of arthritis and osteoarthritis. This drug inhibits COX-1 and COX-2 enzymes. As a result, it reduces pain and inflammation in joints. Diclofenac is usually used as a first line therapy for acute and chronic pain.</p>

<p>Pan-EGFR inhibitor (HER1, HER2 and HER4); antineoplastic</p>

<p>Procarbazine is an alkylating agent used in chemotherapy to treat brain cancer and Hodgkin's lymphoma. It methylates guanine in DNA which causes the strands to become prone to breakage, thus inhibiting both DNA and RNA synthesis. The drug has been shown to be effective in vitro against a variety of human carcinoma cell lines.</p>

<p>Quinapril is an angiotensin-converting enzyme (ACE) inhibitor prodrug that is used to treat hypertension and congestive heart failure. It blocks the conversion of angiotensin I to angiotensin II, resulting in vasodilation which lowers blood pressure.</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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>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>ERKtide Substrate Peptide.</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>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>AKTide-2T is a 14-mer peptide which has the ability to bind to the substrate binding domain of Akt1 with a Ki of 12mM. AKt1 is part of the Akt kinase family which are serine/threonine kinase and it is ubiquitously expressed. AKt1 performs roles such as promoting endothelial neoplasms and through phosphorylating angiogenic substrates AKt1 plays a role in angiogenesis. AKT kinases as a whole perform functional roles in cell proliferation, cell growth, survival and intermediary metabolism.During peptide library screening, AKTide-2T was found to contain the optimal motif for successful binding to AKT. When phosphoamino acid analysis of AKTide-2T was carried out it was observed that although AKTide-2T contained two potential AKT phosphorylation sites: serine or threonine, AKT only phosphorylated the serine site. Furthermore it was found that AKTide-2T exhibits properties of being a competitive inhibitor for example it competitively inhibits histone H2B from being phosphorylated by AKT.</p>

<p>rel-(1R,2S)-8-Bromo-1-(3-bromo-4-hydroxy-5-methoxyphenyl)-1,2-dihydro-7-hydroxy-N2,N3-bis[2-(4-hydroxyphenyl)ethyl]-6-methoxy-2,3-naphthalenedicarboxamide is a synthetic chemical compound, which is derived through targeted organic synthesis and structural optimization efforts. Its source lies in advanced laboratory methodologies designed to enhance specific pharmacological properties. The mode of action is expected to involve selective interaction with particular molecular targets, potentially modulating distinct pathways related to cellular function or signaling processes.</p>

<p>Vardenafil is a phosphodiesterase type 5 inhibitor that binds to intracellular targets and competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis thus increasing cGMP levels. Vardenafil can be used for the research of erectile dysfunction, hepatitis and diabetes.</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>Imipramine is a drug that belongs to the class of tricyclic antidepressant drugs. It is used in the treatment of depression and childhood enuresis. It is a potent inhibitor of serotonin and norepinephrine reuptake. Imipramine blocks D-2 receptors, H1 receptors, α-1 and α-2 adrenergic receptors and muscarinic receptors. Also, it is indicated for dysthymia, attention-deficit disorders, agoraphobia and it is effective in treating anxiety and panic disorders.</p>

<p>A cell permeable inhibitor of oligosaccharyltransferase that interferes with the transfer of mature glycan precursors to recipient proteins. Causes reduced proliferation, G1 arrest and senescence in EGFR- and FGFR-dependent non-small-cell lung carcinoma (NSCLC) cells.</p>

<p>Tocainide is a class 1b antiarrhythmic agent that is used in the treatment of ventricular arrhythmias. This drug acts on sodium channels to decrease the excitability of myocardial cells. This drug also prevents the depolarization of cardiac muscle cells and prolongs their refractory period.</p>

<p>Inhibits the mitochondrial outer mebrane protein mitoNEET, anti-leukaemic</p>

<p>A selective antagonist of serotonin 5-HT2B receptors, inhibiting inositol phosphate formation and calcium release. Blocks 5-HT-induced contraction in rat stomach fundus. Reduces fecal output in vivo, upon inhibition of 5-HT2B by RS 127445, demonstrating a potential role for this receptor in colonic motility. Inhibits visceral hypersensitivity induced by restraint stress or colonic inflammation.</p>

<p>Lisinopril is a drug that belongs to the group of angiotensin converting enzyme (ACE) inhibitors. It is used to treat hypertension, heart failure and myocardial infarction. Lisinopril binds to the active site of the ACE enzyme, preventing it from converting angiotensin I into angiotensin II.</p>

<p>Albuterol is a selective beta-2 adrenergic receptor agonist drug that is used to prevent and treat wheezing, shortness of breath, and other breathing difficulties caused by asthma. It relaxes the muscles in the airways, making them more open. Albuterol also has an anti-inflammatory effect.</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>γ-secretase inhibitor; inhibits notch signaling</p>

<p>Lofepramine is a psychoactive drug that belongs to the class of tricyclic antidepressants. It is used to treat depression and anxiety disorders. This drug works by inhibiting the reuptake of neurotransmitters such as serotonin and norepinephrine and as a result these neurotransmitters remain active in the brain for a longer period, which can help improve mood and alleviate symptoms of depression.</p>

<p>Resiniferatoxin is a natural chemical found in some plants that activates pain receptors.</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>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>Prostaglandin E2 (EP2) receptor antagonist</p>

<p>Inhibitor of IKKβ serine kinase</p>

<p>HMG-CoA reductase inhibitor</p>

<p>A brain-penetrant inhibitor of leucin-rich repeat kinase 2 (LRRK2) with IC50 = 0.76 nM and anti-parkinsonian activity. Gain-of-function mutations in LRRK2 gene lead to increased familial and idiopathic risk of developing the disease. The inhibitors of the kinase activity have therapeutic potential against Parkinson’s disease.</p>

<p>Epalrestat is a carboxylic acid derivative that is used for the treatment of diabetic neuropathy. This drug is an aldose reductase inhibitor and aims to reduce the accumulation of intracellular sorbitol. Studies in rats have shown this drug to improve morphological abnormalities of nerves.</p>

<p>H+/K+ ATPase inhibitor</p>

<p>Alfuzosin is an alpha-1 adrenoreceptor antagonist drug that is used in treatment and management of benign prostatic hyperplasia. This drug works by relaxing the muscles in the prostate and bladder neck which results in symptom improvement.</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>ERKtide Substrate Peptide.</p>

<p>CHZ868 is a chemical compound primarily used in experimental research settings. It is synthesized through a series of organic reactions, often involving specific reagents to ensure high purity and stability. The compound operates by interacting with specific cellular pathways, influencing key biochemical processes that are crucial for its intended applications.</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>DNA alkylating agent; highly potent metabolite of nemorubicin</p>

<p>PAC 1 is a small-molecule apoptosis inducer, derived from synthetic sources, with a unique mode of action targeting the apoptotic pathways in cancer cells. PAC 1 functions by selectively activating procaspase-3, an inactive precursor of the caspase enzymes, which play a crucial role in the execution phase of cell apoptosis. By facilitating the conversion of procaspase-3 to its active form, PAC 1 enhances the apoptotic response in cancer cells, promoting cell death and offering potential therapeutic advantages.</p>

<p>KRAS G12C inhibitor</p>

<p>A chemical probe for the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1). GNE 371 binds TAF1 with an IC50 of 10 nM and is selective over other bromodomain family members. Exerts anti-proliferative effects in synergy with BET inhibitor JQ1.</p>

<p>Phosphodiesterase inhibitor</p>

<p>Induces Kruppel like factor 4 (KLF4) and reduces the expression of MYC.  Anti-tumor activity of APTO 253 has been demonstrated in AML and haematological malignancies. Inducing KLP4 expression in ovarian cancer cells using APT0 253 sensitises cells to cisplatin  and paclitaxel. BRCA1/2-deficient cancer cells are hypersensitive to APTO 253, which mediates its action by causing DNA damage.</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>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>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>A potent and selective inhibitor of cell death-inducing kinase RIP2 (IC50 = 5 nM). Reduces release of pro-inflammatory cytokines. Inhibits production of TNF-α and IL-6 in intestinal explants from patients with Crohn's disease and ulcerative colitis.</p>