Modulateurs d'enzymes

Dihydrocyclosporin A is an immunosuppressant, which is a cyclic undecapeptide derived from fungal metabolites, specifically from the soil fungus Tolypocladium inflatum. This compound functions through the inhibition of calcineurin, which is a crucial phosphatase involved in the activation of T-cells. By binding to the intracellular protein cyclophilin, Dihydrocyclosporin A forms a complex that inhibits calcineurin activity, subsequently blocking the transcription of interleukin-2 and other cytokines essential for T-cell proliferation.

Inhibitor of FLT3 kinase and acid sphingomyelinase

Cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor

Lifirafenib is a targeted anticancer therapy, which is a small molecule inhibitor sourced through pharmaceutical development processes. Its mode of action involves the selective inhibition of the RAF kinase family, including B-RAF, which plays a critical role in the MAPK/ERK signaling pathway. By targeting these kinases, Lifirafenib effectively disrupts the aberrant signaling that contributes to tumor growth and survival in certain cancers with mutations such as BRAF V600E.

TPPB is a small molecule inhibitor, which is synthetically derived for targeted biochemical studies. It functions by selectively modulating G-protein-coupled receptor (GPCR) signaling pathways through the inhibition of specific protein-protein interactions. This mode of action makes TPPB an insightful tool for dissecting the complex mechanisms by which G-proteins relay extracellular signals to intracellular responses.

Tegafur is an antineoplastic agent that is used for the treatment of gastric and colorectal cancers in combination with other medications. This drug is a prodrug of 5-fluorouracil and has anticancer properties by inhibiting thymidylate synthase during DNA synthesis. Additionally, Tegafur causes disruptions of RNA functions.

Tegafur 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&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.

Inhibitor of CKD1, CDK2, and CDK4 serine/threonine kinases

Selective and potent inhibitor of lysine acetyltransferases KAT6A and KAT6B with IC50 values in low nanomolar range. The compound is a reversible competitor of acetyl coenzyme A domain of KAT6A/B enzymes. It inhibits MYST-catalysed histone acetylation and was shown to arrest lymphoma progression in mice models. The compound opened the door to a new class of cancer therapeutics that could potentially direct the cancer cells in senescence or permanent dormancy.

Antagonist of Aurora A serine/threonine protein kinase; antineoplastic

Cyclosporine U is a cyclic polypeptide immunosuppressant, which is a derivative of the natural product Cyclosporine A, produced by the fermentation process involving the filamentous fungus *Tolypocladium inflatum*. It primarily acts by inhibiting the activity of calcineurin, a phosphatase enzyme, which in turn blocks the transcription of interleukin-2 and other cytokines. This mechanism suppresses the activation of T-lymphocytes, a crucial component in the immune response.

N-alpha-Benzoyl-L-argininamide is a synthetic compound that is used as an enzyme inhibitor. It binds to the active site of proteases, thereby inhibiting their activity. This drug has been shown to inhibit the activities of phosphodiesterase and phosphatase enzymes in vitro. N-alpha-Benzoyl-L-argininamide also inhibits the proteolytic degradation of hippuric acid and casein in vitro. The binding affinity for this drug is due to its structural similarity with substrates such as glutamate and rhizosphere exudates.

First generation PI 3-kinase inhibitor

Inhibitor of the histone methyltransferase SETD8 that supresses methylation of the K20 residue in histone 4. UNC 0379 treatment of human glioma reduced recruitment of 53BP1 protein to double strand breaks and sensitised cells to radiotherapy without altering cell cycle kinetics.

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.

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.

Aurora kinase inhibitor

Inhibitor of FGFR kinase

PI3K/mTOR kinase inhibitor; anti-neoplastic

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.

Inhibitor of myosin?II?specific ATPase which blocks the myosin heads in an actin-detached state, disrupts contractility of myosin-actin filaments and stabilizes super-relaxed state of muscle fibres. It inhibits skeletal muscle myosin, non-muscle myosin II and heart muscle myosin.

Ruxolitinib is a janus tyrosine kinase inhibitor active specifically on sub-types JAK1 and JAK2 with IC50 values in the nanomolar range. JAK1 and JAK2 are kinases involved in the regulation of hematopoiesis. Clinically applied to the treatment of intermediate and high-risk myelofibrosis, ruxolitinib is usually well tolerated by patients.

Phosphorylated EGFR peptide substrate.

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.

Inhibits Jak kinases; immunosuppressive; anti-inflammatory

Nafamostat is a broad-spectrum serine protease inhibitor produced by chemical synthesis. Nafamostat is effective through its antioxidant and anti-inflammatory activity. This drug is involved in inhibiting various enzyme systems such as coagulation and fibrinolytic systems.

Inhibits lysophosphatidylserine hydrolysis by the integral membrane serine hydrolase ABHD12 (IC50 = 1.3 µM). Raised levels of lysophosphatidylserine were observed in mouse brain in vivo and in primary human macrophages. DO 264 had proinflammatory effects, following infection with lymphocytic choriomeningitis virus (LCV) clone 13 in mice, resulting in severe inflammatory lung damage.

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.

HMG-CoA reductase inhibitor; anti-hypercholesterolemia agent

Parecoxib is a COX-2 inhibitor and belongs to the group of pharmacological agents. It is a prodrug of valdecoxib that is used for the treatment of osteoarthritis and rheumatoid arthritis, as well as other conditions where the reduction in pain and inflammation are desired.

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

Potent inhibitor of dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) with IC50 value of 0.7 nM. Elevates hemoglobin and platelet levels in anemic mice.

A potent and selective covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4). This receptor tyrosine kinase activates an oncogenic driver in hepatocellular carcinoma, the fibroblast growth factor 19 (FGF19). The FGFR4 inhibitor is therefore a promising candidate for the treatment of advanced liver cancer.

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.

Inhibitor of dipeptidyl peptidase IV; anti-diabetic agent

Inhibitor of dopamine-?-hydroxylase

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.

Inhibitor of fibroblast growth factor receptors (FGFR1, FGFR2 and FGFR3). Demonstrated anti-tumor effects in pre-clinical models of FGFR-driven tumors. AZD 4547 resulted in tumor progression when applied on a patient-derived model of FGFR1-amplified squamous cell lung disease. Antineoplastic effects also observed in FGFR2-amplified gastric cancer.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to reduce inflammation, relieve pain and reduce fever. The mechanism of action of ibuprofen has not been fully elucidated, but it may be due to inhibiting the enzyme cyclooxygenase and thus decreasing the synthesis of prostaglandins allowing a reduction of pain and inflammation.

Dasatinib is a potent inhibitor of tyrosine kinases and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancer. It also inhibits many SRC- family kinases. Dasatinib has been shown to inhibit the proliferation of cancer cells, leading to cell lysis. Additionally, it has anti-angiogenic effects in vivo, inhibiting the development of new blood vessels in solid tumours.

Inhibitor of BCR-ABL1 kinase

Sunitinib is a tyrosine kinase inhibitor drug. It is a drug that is used as a treatment for renal cell carcinoma, gastrointestinal stromal tumor, and other solid tumors. This drug inhibits tyrosine kinases such as VEGFRs, this prevents tumour growth and pathologic angiogenesis.

PD 168393 is a potent and selective irreversible inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. It is synthesized through advanced chemical processes, designed to specifically target and covalently modify the ATP-binding site of EGFR. The mode of action involves the irreversible binding to the cysteine residue in the ATP-binding pocket, leading to the inhibition of EGFR autophosphorylation and subsequent downstream signaling pathways.

Inhibitor of glutaminase; glutamine analogue

Potent and selective GSK3-β inhibitor, with IC50 value of 48 nM. Increases Nanog expression and regulates self-renewal in murine embryonic stem cells (ESCs). Induces reprograming of induced pluripotent stem cells (iPSCs) to derive cells from specific lineages.

Nintedanib is an anti-inflammatory and anti-cancer drug. It is used for treatment of idiopathic pulmonary fibrosis. Nintedanib is a prodrug that is rapidly converted to the active form nintedanib, which inhibits angiogenesis by interfering with the activation of vascular endothelial growth factor receptor 1 (VEGFR1). 
Nintedanib 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&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.

Arbutin or alpha-arbutin is a natural product. It is a hydroquinone glucoside with antioxidant properties. It is widely used in cosmetics as depigmenting agent, acting as an inhibitor of tyrosinase in melanocytes. Arbutin acts by supressing the enzymes that stimulate these melanocytes without killing or fully inhibiting them. As a consequence, melanin production is decreased to avoid hyperpigmentation that might be caused by an excess of UV radiation or a higher activity of tyrosinases.

Inhibitor of panPI3K/mTOR

HIF prolyl-hydroxylase inhibitor for treatment of anaemia

Inhibitor of LRRK2 kinase

Inhibits VEGFR1, VEGFR2, VEGFR3, c-kit and PDGFR tyrosine kinases

A potent ATP-competitive inhibitor of tropomyosin-related kinases (TRK1, TRK2 and TRK3), members of the receptor tyrosine kinase family of neurotrophin receptors. Tumors with oncogenic TRK fusions are sensitive to larotrectinib, leading to reduced proliferation and tumor growth in patients with soft tissue sarcoma, triple-negative breast cancer and lung cancer.

Vildagliptin is an antihyperglycemic agent that is used for the management of type 2 diabetes mellitus. This drug is a dipeptidyl peptidase 4 inhibitor and prevents the degradation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This leads to improved glycemic control.

Inhibitor of CK2 protein kinase; anti-proliferative

Inhibitor of dihydroorotate dehydrogenase; anti-inflammatory; immunomodulatory

Forskolin is a compound derived from the medicinal plant Coleus forskohlii. As an activator of adenylate cyclase, Forskolin causes increases cellular levels of cAMP, and can be used in cell physiology research. It also has antihypertensive, platelet aggregation inhibitory and smooth muscle relaxant effects.

NButGT (N-butyryl-glucosamine-1,5-lactone O-(phenylcarbamoyl)oxime) is a selective inhibitor of O-GlcNAcase (OGA), the enzyme responsible for removing O-linked N-acetylglucosamine (O-GlcNAc) modifications from proteins. It effectively increases O-GlcNAc levels in cells and tissues without altering hexosamine biosynthetic pathway enzyme expression. It has also been shown that NButGT rapidly increases O-GlcNAcylation of mitochondrial proteins involved in oxidative phosphorylation and metabolism. While effective, NButGT served as a precursor to more potent OGA inhibitors like Thiamet-G. These findings highlight NButGT's importance as a tool for studying O-GlcNAcylation in various biological contexts, particularly in cardiac and neurological research. For example, in recent cardiac studies, NButGT pretreatment has demonstrated an improvement in cardiac output and mitochondrial respiration when combined with epinephrine.

Inhibits phorbol ester TPA/PMA; immunosuppressant

Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic

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.

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.

Brinzolamide is a carbonic anhydrase inhibitor this is used for the treatment of ocular hypertension and glaucoma. Inhibition of carbonic anhydrase slows the formation of bicarbonate ions and as a result of this, it slows fluid flow in the eye, lowering the intraocular pressure. It has a high lipophilicity to enable diffusion across the blood-retinal barrier.

Inhibitor of PIP5K1C

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.

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.

Inhibitor of VEGF receptor tyrosine kinases and non-receptor tyrosine kinases