Enzyme Modulators

<p>Abiraterone is an antiandrogen drug used in the treatment of metastatic prostate cancer. It is a derivative of steroidal progesterone. This drug inhibits the enzyme CYP17 irreversibly, thus inhibiting the synthesis of androgen. It specifically inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone to decrease serum levels of testosterone and other androgens.</p>

<p>Topoisomerase II inhibitor; chemotherapeutic drug</p>

<p>Inhibits multiple receptor tyrosine kinases (RTKs), including c-Kit, PDGFRβ, PDGFRα, c-Met, and Axl. Sitravatinib inhibits proliferation of sarcoma cells and reduced tumor growth in vivo. Promotes immune response in tumor microenvironment and enhances sensitivity to immune checkpoint inhibitors. This compound is undergoing several clinical trials as a potential anti-cancer therapeutic agent.</p>

<p>Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic</p>

<p>Inhibitor of ecto-ATPase which blocks the hydrolysis of nucleoside diphosphates and triphosphates in extracellular space. The compound inhibits NTPDase1, NTPDase 3, NTPDase 8 and NPP1and prolongs the effect of ATP on purinergic P2 receptors in environment with physiological concentrations of nucleotides. The compound has variable effectiveness as ecto-ATP inhibitor in mouse, rat, human and guineia pig tissues.</p>

<p>Inhibitor of AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase)</p>

<p>Inhibitor of Aurora kinases A, B and C</p>

<p>O6-Benzylguanine is a guanine analog that is an antineoplastic agent. It works by acting as a suicide inhibitor of the enzyme O6-alkylguanine-DNA alkyltransferase. This results to an interruption of DNA repair so that damage can occur to local tumor targets.</p>

<p>Inhibitor of 3β-hydroxysteroid dehydrogenase in steroid biosynthesis</p>

<p>Potent and selective MAP/ERK kinase 1/2 inhibitor. Reduces growth of tumor cells with B-Raf and Ras mutations. Tumor regression observed after chronic treatment in in vivo xenograft models. Enhances anti-tumor effect in combination with irinotecan or docetaxel.</p>

<p>Etoposide is a cytotoxic drug used in cancer chemotherapy. It inhibits DNA replication through inhibition of DNA topoisomerase II, thus catalysing cell cycle arrest and apoptosis. <br>Etoposide 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>Oxaprozin is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis and rheumatoid arthritis. This drug relieves swelling and inflammation by inhibiting the enzyme cyclooxygenase which in turn inhibits prostaglandin synthesis.</p>

<p>Phosphodiesterase (PDE5, 6, 9 and 11) inhibitor</p>

<p>Pan-class I phosphatidylinositide 3-kinase (PI3K) inhibitor (IC50 = 3, 33, 3 and 75 nM at catalytic subunits p110α, p110β, p110δ and p110γ respectively). Inhibits proliferation in several cancer cell lines, such as glioblastoma, breast and prostate cancer cells. Has synergistic anti-cancer effect in combination with MEK/ERK kinase inhibitor GDC-0973 (cobimetinib).</p>

<p>Pan-tyrosine kinase inhibitor (VEGFR2, c-MET, RET, KIT); anti-neoplastic</p>

<p>A potent small-molecule activator of UNC-51-like kinase 1 (ULK1), a serine-threonine kinase involved in autophagy. Promotes cytoprotective autophagy in MPP+-treated SH-SY5Y cells, via the ULK complex. Improves motor dysfunction and reduces loss of dopaminergic neurons, mediated by MPTP, in in vivo models of Parkinson’s disease.</p>

<p>Lestaurtinib is a multitarget tyrosine kinase inhibitor of the JAK, FLT-3 and TrkA families of tyrosine kinases at nanomolar concentrations. It inhibits proliferation and induces apoptosis in vitro. Lestaurtinib is a FDA approved orphan drug for acute myeloid leukemia.</p>

<p>Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) protein. This inhibition is on the EGFR tyrosine kinase domain, where Gefitinib bindings to the ATP-binding site. As a a tyrosine kinase inhibitor, Gefitinib blocks tumor growth and has led to its use in slowing the progression of non-small cell lung cancer. Gefitinib also inhibits invasion and metastasis through inhibition of macrophage receptor interacting protein kinase 2 (RIPK2), rather than EGFR.</p>

<p>Inhibitor of PDE4 enzyme</p>

<p>Inhibitor of dioxygenase IDO1</p>

<p>Inhibitor of vacuolar-type proton pump</p>

<p>N-Desmethyl ibandronate sodium is a white crystalline solid with a melting point of 238-240 °C. It has versatile building block, complex compound and research chemicals applications. It is an intermediate used in the synthesis of other compounds, such as speciality chemicals, useful intermediates and useful scaffolds. N-Desmethyl ibandronate sodium can be used in reactions that require high quality and high purity products.</p>

<p>Nabumetone is a non-steroidal anti-inflammatory drug that is used in the treatment of osteoarthritis and rheumatoid arthritis. This drug is also a cyclooxygenase inhibitor and works by inhibiting this enzyme so that pain and inflammation is reduced.</p>

<p>Potent and selective inhibitor of the glycogen synthase kinase GSK-3. Promotes cell renewal in embryonic stem cells by modulating Notch, MAPK and TGF-β signalling pathways, which are involved in pluripotency. It also affects the Wnt/β-catenin pathway and alters expression of genes coding for proteins, epigenetic regulatory elements and non-coding RNAs. The combination of CHIR 99021 and basic fibroblast growth factor (bFGF) allows long-term self-renewal in adult mouse retinal progenitor cells.</p>

<p>(Z)-Mycophenolic acid is an immunosuppressive agent derived from the fermentation of fungi, primarily from the Penicillium species. It functions by inhibiting inosine monophosphate dehydrogenase (IMPDH), an enzyme crucial for de novo purine synthesis. This selective blockade of IMPDH specifically affects lymphocyte proliferation due to their heavy reliance on this pathway for DNA synthesis, thereby exerting its immunosuppressive effects.</p>

<p>Selective and potent inhibitor of lysine acetyltransferases KAT6A and KAT6B with IC50 values of 8 nM and 28 nM, respectively. The compound is a reversible competitor of acetyl coenzyme A domain of KAT6A/B enzymes. It inhibits MYST-catalysed histone acetylation and potentiates senescence in vitro and in zebrafish model of hepatocellular carcinoma. The compound opened the door to a new class of cancer therapeutics that could potentially direct the cancer cells in senescence or permanent dormancy.</p>

<p>Bruton's tyrosine kinase antagonist; reduces Fcγ receptor signaling</p>

<p>Inhibitor of VEGFR, PDGR, c-Kit and Ret; inhibitor of angiogenesis</p>

<p>Inhibits p38 MAP kinase; anti-inflammatory; neuroprotective</p>

<p>Crizotinib is a drug that belongs to the group of tyrosine kinase inhibitors. It is used in the treatment of cancers, including non-small cell lung cancer, small cell lung cancer, and other types of solid tumours. Crizotinib inhibits the activity of the tyrosine kinase ALK or anaplastic lymphoma kinase, which is involved in many signalling pathways and biological processes. The inhibition of this enzyme leads to decreased energy metabolism, reduced mitochondrial membrane potential and increased susceptibility to apoptosis.</p>

<p>Potent and specific inhibitor of the tyrosine protein kinase Mer precursor (MERTK) with 38-fold selectivity over the FMS-like protein kinase FLT3. UNC 4203 inhibits MERTK with an IC50 value of 2.4 nM and shows favourable pharmacokinetic properties. In vivo experiments in mice showed that UNC 4203 dramatically decreased the phosphorylation of MERTK in bone marrow leukemia cells.</p>

<p>Benazepril is a nonsteroidal anti-inflammatory drug that can be used to treat hypertension, heart failure and renal failure. It is an angiotensin-converting enzyme (ACE) inhibitor that blocks the conversion of angiotensin I to angiotensin II. This inhibition prevents the vasoconstrictive effects of this peptide, which are mediated through activation of the renin-angiotensin system.</p>

<p>Inhibitor of metalloendopeptidase neprilysin</p>

<p>Finasteride is an antiandrogenic drug that belongs to the group of 5-alpha reductase inhibitors, which are used for the treatment of benign prostatic hyperplasia and male pattern baldness. The conversion of testosterone to 5α-dihydrotestosterone (DHT) is blocked by type II 5α-reductase inhibition, which then results in significant increase in prostatic testosterone concentrations and minimal to moderate increases in serum and tissue DHT concentrations. A reduction in DHT concentration will cause a reduction in prostatic volume as DHT appears to be the main androgen responsible for stimulating prostatic growth.</p>

<p>A selective inhibitor of MEK1/2 kinase. Anti-proliferative and pro-apoptotic in multiple myeloma (MM) cells via G0/G1 cell cycle arrest and caspase 3 and PARP cleavage, respectively. Synergistic with other anti-MM therapies. Has anti-tumor effects in some solid tumors, such as in K-ras mutated colorectal cancer.</p>

<p>Methotrexate is a chemotherapeutic and immunosuppressive medication, which is a synthetic analog of folic acid. Its source is through chemical synthesis, mimicking the structure of dihydrofolate in order to exert its effects. Methotrexate acts primarily by inhibiting the enzyme dihydrofolate reductase (DHFR), leading to a decrease in tetrahydrofolate production. This disruption in folate metabolism results in the inhibition of DNA, RNA, and protein synthesis, which affects rapidly dividing cells.Methotrexate is employed broadly in clinical oncology as an antineoplastic agent, particularly in the treatment of leukemias, lymphomas, breast cancer, and osteosarcoma. Additionally, it serves as a cornerstone for managing autoimmune diseases such as rheumatoid arthritis and psoriasis, where it helps modulate the aberrant immune response. The dual role of Methotrexate in oncology and immunosuppression underscores its versatility and critical importance in therapeutic regimens. However, its use demands careful monitoring due to potential adverse effects on non-cancerous cells and organ systems, necessitating precise dosage management and patient evaluation.</p>

<p>Farnesyl pyrophosphate synthase inhibitor</p>

<p>Phosphodiesterase 5 inhibitor; anti-impotence drug</p>

<p>Indomethacin is a nonsteroidal anti-inflammatory drug that inhibits the production of prostaglandin PGE2. It is used to treat pain, fever, and inflammation. Indomethacin's mechanism of action is not well understood, but it may be due to interference with the ability of PMNs to bind to the surface of bacteria or to release reactive oxygen species. The drug has been shown to reduce mitochondrial membrane potential in mammalian cells, leading to apoptosis. This effect on mitochondria may also contribute to Indomethacin's anti-inflammatory effects. Indomethacin 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>Inhibits JAK1 and JAK2 kinases</p>

<p>Roflumilast is a selective phosphodiesterase-4 inhibitor that is used for the treatment of exacerbations in patients with chronic obstructive pulmonary disease (COPD). It is also used to treat plaque psoriasis. This drug has anti-inflammatory and immunomodulatory effects as it aids in increasing levels of cAMP.</p>

<p>MLN 4924 is a selective small molecule that acts as an inhibitor of the Nedd8-activating enzyme. This compound is synthetically derived and functions by inhibiting the conjugation of Nedd8 to cullin proteins. By blocking this pathway, MLN 4924 disrupts the activity of the SCF (Skp, Cullin, F-box containing complex) E3 ubiquitin ligase, leading to an accumulation of proteins that can induce apoptosis and cell cycle arrest.</p>

<p>BRAF kinase inhibitor; antineoplastic</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>Toceranib phosphate is a receptor tyrosine kinase inhibitor. Toceranib phosphate has been shown to be effective in the treatment of skin cancer and other types of cancer, including lung cancer and breast cancer. It is approved in the US as a treatment for canine mastocytoma (mast cell tumours).</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>Inhibitor of caspases; broad spectrum</p>

<p>Selective c-Met kinase inhibitor</p>

<p>Sorafenib is a drug that belongs to the class of multikinase inhibitors. It inhibits a number of kinases, including the Mcl-1 protein, which is involved in apoptosis along with blocking picolinic acid (PA), an endogenous metabolite involved in apoptosis signal transduction. Sorafenib also binds to epidermal growth factor receptor (EGFR) on the surface of cancer cells, inhibiting the production of proteins that are required for angiogenesis, thus blocking the formation of new blood vessels. Sorafenib may also inhibit P-glycoprotein (Pgp) activity. Overall, these cytotoxic effects give Sorafenib anti-tumor properties, inhibiting angiogenesis and cellular transformation, which are the two main processes of tumor growth and metastasis. Sorafenib has been shown to be effective against a range of solid tumors such as breast, prostate and lung cancers and is also used for the treatment of metastatic colorectal cancer and renal cell carcinoma. A combination therapy group found that sorafenib was more effective when used with interferon alfa-2b for the treatment of advanced renal cell carcinoma. Sorafenib also has the potential for drug interactions with other drugs that are metabolized by cytochrome P450 enzymes.<br>Sorafenib 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>Seratrodast is a thromboxane receptor antagonist that is used to treat asthma. However, this drug does not affect thrombus formation as other thromboxane synthase inhibitors do such as ozagrel.</p>

<p>Lumiracoxib is a COX-2 selective non-steroidal anti-inflammatory drug that is used for the treatment of osteoarthritis. This drug inhibits prostaglandin synthesis via inhibition of COX-2.</p>

<p>Receptor tyrosine kinase inhibitor; anti-angiogenesis; anti-oncogenesis</p>

<p>Afatinib is a small molecule that inhibits the activity of cellular kinases that are involved in the progression of cancer. It is an Irreversible inhibitor of three members of the ErbB family. This molecule binds covalently to cysteine 797 residue in HER2 and blocks downstream cellular signalling which inhibits cellular growth and promotes apoptosis. It has been researched for the treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer and colorectal cancer.</p>

<p>Camostat is a serine protease inhibitor that is used for the treatment of chronic pancreatitis. This drug has shown to reduce inflammation and pain. Studies have shown that Camostat has also inhibited the entry of SARS-CoV-2 in lung cells by inhibiting the priming process of S-protein, necessary for the viral entry into host cells.</p>

<p>LOXO-305 is a small molecule inhibitor, which is a synthesized chemical compound designed to selectively target specific enzymes or pathways. Its source is rooted in medicinal chemistry and pharmacological research aimed at elucidating pathways involved in oncogenesis.</p>

<p>Specific inhibitor of glycogen synthase kinase 3 (GSK-3) with IC50 in low nanomolar range. Studies showed that BIO maintains self-renewal in embryonic stem cells (ESCs) as well as increases activity of β-catenin. In neonatal cardiomyocytes, BIO promotes cell cycle by stimulating cell entry into S phase as well as cytokinesis. In germline stem cells from female mice (FGSCs), BIO promoted proliferation and maintenance of FGSCs by activating β-catenin and up-regulating E-cadherin.</p>

<p>Anastrozole is a non-steroidal drug that belongs to the class of aromatase inhibitors. It inhibits the production of estrogen by blocking the conversion of androgens to estrogens in peripheral tissues. The drug has been shown to be effective in treating breast cancer in postmenopausal women. In vitro assays have shown that Anastrozole can inhibit tumor growth as well as induce apoptosis in human serum cells, which suggests that it may be effective against a variety of cancers.</p>

<p>VEGFR2 a tyrosine kinase receptor inhibitor; antineoplastic</p>

<p>Inhibitor of ERK1 and ERK2 kinases</p>

<p>RIPK2 protein kinase inhibitor; EGFR inhibitor</p>

<p>Inhibits type III tyrosine kinases (PDGFRα, PDGFRβ, FLT3)</p>

<p>A reversible inhibitor of IGF-1R kinase and insulin receptor. Has anti-growth effects in mesenchymal, epithelial and hematopoietic tumor types. Synergistic with other cytotoxic, hormonal and targeted anti-cancer therapy.</p>

<p>Irsogladine is a gastroprotective drug that is used for the treatment of GERD and gastric ulcers. This drug also has antioxidant properties. Irsogladine is a phosphodiesterase-4 inhibitor and increases levels of cAMP. It helps to prevent and heal damage to the stomach lining.</p>

<p>Inhibitor of human neutrophil elastase</p>

<p>Inhibits MET, VEGFR1-3, Tie and Ron tyrosine kinases; antineoplastic</p>

<p>Thioglycosyl Naphthalimide is a highly potent human O-GlcNAcase (hOGA) inhibitor with good selectivity against human β-N-acetylhexosaminidase B (HsHexB).</p>

<p>Acetylcholinesterase inhibitor; therapy for Alzheimer's disease</p>

<p>Rofecoxib is a non-steroidal anti-inflammatory drug that is used to treat osteoarthritis, acute pain and migraine attacks. This drug is also a COX-2 inhibitor. As a result, it reduces inflammation and pain.</p>

<p>γ-secretase inhibitor; inhibits notch signaling</p>

<p>Specific inhibitor of the ubiquitin specific protease-7 (USP7), which is a validated deubiquitinase of the E3 ubiquitin-protein ligase MDM2. The compound inhibits the USP7 deubiquitinase activity by binding to acidic amino acid residues important for the interaction with ubiquitin. Induces tumor cell death and enhances cytotoxicity of chemotherapeutic agents.</p>

<p>Idelalisib is a pharmaceutical drug that functions as a PI3Kδ inhibitor, developed through synthetic chemical processes. Its mode of action involves selectively targeting and inhibiting phosphatidylinositol 3-kinase delta (PI3Kδ), a lipid kinase that plays a crucial role in the signaling pathways responsible for cell proliferation, survival, and differentiation. By inhibiting this enzyme, Idelalisib effectively impedes pathways that are often hyperactivated in certain hematologic malignancies, thereby exerting antitumor effects.</p>

<p>Inhibitor of p38 kinase</p>

<p>Inhibitor of isocitrate dehydrogenase 2</p>

<p>Inhibits multiple tyrosine kinases (Abl1, Src family kinases, Tie-2 and VEGFR-2)</p>

<p>A potent inhibitor of phosphodiesterase type 9 (PDE9) tested in human and murine in vitro assays (IC50 values: 55 nM and 100 nM respectively). BAY 73-6691 induces long-term potentiation and improves memory in rodents. Has therapeutic potential for Alzheimer’s disease.</p>

<p>Nilotinib is a kinase inhibitor that is used for the treatment of Chronic Myeloid Leukemia (CML). This drug is also used for the treatment of CML that is resistant to imatinib. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. It also inhibits PDGFR and c-kit.</p>

<p>Ebselen is a non-toxic organoselenium compound with antioxidant, anti-inflammatory and cytoprotective properties. Ebselen is an inhibitor of lipoxygenases, nitric oxide (NO) synthases, protein kinase C, H+/K+-ATPase, thioredoxin reductase and NADPH oxidase. Recently, ebselen has been identified by several studies as a covalent inhibitor of the main protease Mpro from coronaviruses. For the SARS-CoV-2 main protease Mpro, the IC50 value is 0.67 μM and EC50 is 4.57 μM.</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>Inhibitor of BACE1 protease</p>

<p>Potent agonist of a1β1γ1 5′-adenosine monophosphate-activated protein kinase (AMPK). It binds to the allosteric drug and metabolite (ADaM) site at the α- and β- subunit interface of AMPK. It has potential for the treatment of diabetic nephropathy. PF 06409577 reduces infections caused by flaviviruses, mediated by changes in the metabolism of lipids in host cells.</p>

<p>Malotilate is a pharmacological agent that is used to treat symptoms of hepatitis, bowel disease, and collagen diseases. This drug reduces collagen synthesis and cell migration activity of fibroblasts in vitro. It also has been shown to facilitate liver regeneration in rats.</p>

<p>Inhibitor of glycogen synthase 3 (GSK-3) and cyclin-dependent kinases CDK1, CDK2 and CDK5. Kenpaullone can substitute transcription factor Klf4 in reprogramming of fibroblast to induced pluripotent stem cells when using the method of ectopic expression of transcriptional factors. In an in vitro model for Alzheimer’s disease, kenpaullone decreased production of amyloid beta peptides Aβ40 and Aβ42.</p>

<p>Inhibitor of EIF2AK3/PERK kinases</p>

<p>(S)-Mephenytoin is a substrate of cytochrome P450 enzyme CYP2C19 (a hydroxylase). It is an effective anticonvulsant that improves control of seizures in patients. According to studies, the drug exhibits a genetic polymorphism in CYP2C19 that results in reduced metabolism in some individuals.</p>

<p>Potent inhibitor of γ-secretase. LY 411575 inhibited production of amyloid β (Aβ) peptides with IC50 of 0.078 nM in vitro as well as decreased levels of Aβ40 and Aβ42 amyloids in brain of a mouse model for Alzheimer’s disease. In vitro studies confirmed that LY 411575 inhibited cleavage of Notch receptor at S3 site with IC50 of 0.39 nM, which blocked Notch activation and downstream signalling, leading to apoptosis in primary and immortalized Kaposi's sarcoma cells.</p>

<p>Analeptic</p>

<p>Etodolac is a non-steroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis and rheumatoid arthritis. It is also used to treat acute pain. This drug works by inhibiting prostaglandin synthesis from the inhibition of the enzyme cyclooxygenase.</p>

<p>Inhibitor of protein kinase CK2</p>

<p>6-Thioguanine is a purine analog used in the therapy for leukemia and for remission consolidation in patients with acute nonlymphocytic anemia. This drug also has antimetabolite action. It replaces guanine during DNA replication. This substitution disrupts the accurate pairing of DNA bases, leading to errors in DNA replication and hinders cell division.</p>

<p>Inhibitor of glutathione peroxidase GPX4</p>

<p>Inhibits RNAPII-mediated trasncription; immunosuppressant; anti-inflammatory</p>