Enzyme Modulators

<p>Fludarabine triphosphate trisodium is a nucleotide analog, which is a type of chemotherapy agent derived from purine nucleosides. This compound is the active metabolite of fludarabine, sourced from synthetic chemistry designed to mimic naturally occurring nucleotides involved in DNA replication. The mode of action involves its incorporation into the DNA strand during replication, where it effectively inhibits DNA polymerase and ribonucleotide reductase. This disruption impairs DNA synthesis, leading to apoptosis or programmed cell death, particularly in rapidly dividing cancer cells.</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>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>Inhibits tankyrase (TNKS1 and TNKS2 with IC50 values of 11 and 4 nM respectively), by binding to the catalytic poly-ADP-ribose polymerase (PARP) domain. This stabilizes cytoplasmic protein Axin, mediating β-catenin depletion and thereby suppresses Wnt signalling pathway. XAV 939 has anti-proliferative and pro-apoptotic effects on neuroblastoma and colorectal cancer cells.</p>

<p>Inhibitor of dioxygenase IDO1</p>

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

<p>Farnesyl pyrophosphate synthase inhibitor</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>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>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>Inhibitor of PDE4 enzyme</p>

<p>Inhibitor of Aurora kinases A, B and C</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>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>Inhibitor of AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase)</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>Proteosome inhibitor; pro-apoptotic; has anti-myeloma activity</p>

<p>Phosphodiesterase 5 inhibitor; anti-impotence drug</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>Phosphodiesterase inhibitor</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>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 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>Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic</p>

<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>Diacerein is a slow-onset anthraquinone IL-1 inhibitor that is used in the treatment of joint diseases such as osteoarthritis. This drug is also being studied for the treatment of insulin resistance and diabetes mellitus. Diacerein works to decrease inflammation and cartilage destruction by reducing the level of interleukin-1.</p>

<p>Inhibitor of cytochrome P450; inhibitor of prostaglandin synthesis</p>

<p>Imiquimod is a toll-like receptor 7 agonist drug that is used for the treatment of genital warts, basal cell carcinoma and condyloma acuminata. This drug works by relieving and controlling wart production. Studies in mice have shown that this drug may induce cytokines such as interleukins. Imiquimod helps to increase apoptosis of diseased tissues and an infiltration of lymphocytes into tumor lesions.</p>

<p>Inhibits phorbol ester TPA/PMA; immunosuppressant</p>

<p>Lenalidomide is a thalidomide derivative that is used to treat multiple myeloma and anemia. This drug exerts immunomodulatory effects by altering cytokine production. Lenalidomide also directly inhibits the cullin ring E3 ubiquitin ligase complex.</p>

<p>Leflunomide is a pyrimidine synthesis inhibitor drug that is used to treat rheumatoid arthritis. Although its mechanism of action is not fully determined, this drug has shown to interfere with cell cycle progression by inhibiting dihydroorotate dehydrogenase and has shown antiproliferative activity. As a result of this, it interferes with the expansion of activated autoimmune lymphocytes. Additionally, Leflunomide is a tyrosine kinase inhibitor.</p>

<p>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.</p>

<p>Inhibitor of oxidative phosphorylation which acts on the F0F1 ATP synthase in the inner mitochondrial membrane and causes acute increase in mitochondrial membrane potential. Gboxin was shown to accumulate in mitochondria of cancer cells, to cause cellular toxicity and cell growth inhibition in mouse glioblastoma. However, Gboxin did not inhibit growth of mouse embryonic fibroblasts or neonatal astrocytes.</p>

<p>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.</p>

<p>Inhibits FGFR family of kinases; antineoplastic; anti-angiogenic</p>

<p>Pravastatin is an HMG-CoA reductase inhibitor that is used to lower lipid levels and manage cardiovascular events such as strokes and myocardial infarction. This drug inhibits HMG-CoA reductase allowing for a reduction in the level of cholesterol.</p>

<p>Inhibitor of CDK2, JAK2 and FLT3; anticancer</p>

<p>Inhibits aromatic amino acid decarboxylase</p>

<p>Adefovir is an antiviral acyclic nucleoside phosphonate (ANP) analogue that works by blocking reverse transcriptase. This drug is used to treat infections associated with Hepatitis B.</p>

<p>Inhibits MEK1 and MEK2 kinases; targeted therapy for melanoma</p>

<p>Pomalidomide is an immunomodulatory agent that inhibits transcriptional regulation by interacting with the pomalidomide-binding protein, which prevents its interaction with RNA polymerase II and thereby prevents DNA transcription. The study with U266 cells demonstrated that pomalidomide targets CRBN, part of an E3 ligase complex, and inhibits its autoubiquinitation and supresses a critical gene (IRF4, interferon regulatory factor 4) for myeloma cell growth with concentrations up to 10 μM. In vitro assays have shown that pomalidomide has inhibitory effects on cell signaling pathways, such as the NF-κB pathway. Pomalidomide also decreases the production of proinflammatory cytokines, such as TNFα and IL-1β, by inhibiting their synthesis or their release from activated monocytes. Recently, the promoting effect of pomalidomide, as its analog lenalidomide, on erythropoiesis (production of red blood cells) has been investigated, demonstrating positive results for its use as a potential new therapy agent for β-hemoglobinopathies.<br>Pomalidomide 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>Febuxostat is a non-purine xanthine oxidase inhibitor that is used for the treatment and management of hyperuricemia and chronic gouty arthritis. Febuxostat inhibits the uptake of uric acid from the blood into cells and thereby reduces its concentration in plasma. Additionally, this drug has been shown to have anti-inflammatory and antioxidant effects.</p>

<p>Inhibitor of DNA topoisomerase I</p>

<p>Inhibitor of Factor Xa; anti-thrombotic</p>

<p>Inhibits proto-oncogene Pim kinases (Pim-1, Pim-2 and Pim-3); antineoplastic</p>

<p>Inhibitor of guanylyl cyclase</p>

<p>Omeprazole is a proton pump inhibitor (PPI) that inhibits the production of gastric acid in the stomach. This is due to Omeprazole binding through a stable disulphide bond to the H+/K+ ATPase enzyme found on parietal cells, and preventing hydrogen ion transport. Consequently, gastric acid secretion is supressed. As a PPI, Omerprazole can be used to treat disorders where gastric acid is over-secreted. Examples of these disorders are gastroesophageal reflux disease (GERD) and peptic ulcer disease.</p>

<p>LW-II-41-27 is a novel Eph receptor tyrosine kinase inhibitor used for cancer treatment.</p>

<p>NADPH oxidase inhibitor; anti-inflammatory</p>

<p>Specific inhibitor of the phosphoinositide 3-kinase (PI3K) alpha subunit with IC50 of 32 nM. In heart muscle it negatively regulates hypertrophic growth, causes increase in late sodium current and leads to arrhythmias. In tumours it inhibits the p110α subunit of PI3K and blocks growth factor signalling resulting in reduced tumour growth.</p>

<p>Inhibitor of COX-1 and COX-2 cyclooxygenases</p>

<p>Lapatinib is an antineoplastic agent used to treat breast and lung cancer. This drug is also a tyrosine kinase inhibitor and inhibits human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1). Lapatinib has shown to inhibit ERBB-driven tumor cell growth in vitro and in various animal models.</p>

<p>An irreversible GSK-3β inhibitor that reduces phosphorylation of tau proteins, protects from neuronal loss and has cognitive and behavioural benefits in murine models. Studied for its potential as a therapeutic agent in Alzheimer’s disease and other neurodegenerative diseases. Tideglusib was also shown to inhibit the main protease Mpro from the SARS-CoV-2 virus with IC50 of 1.55 μM.</p>

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

<p>Inhibitor of dihydroorotate dehydrogenase; anti-inflammatory; immunomodulatory</p>

<p>Inhibitor of CK2 protein kinase; anti-proliferative</p>

<p>A selective and potent inhibitor of phosphodiesterase 2 (PDE2). Raises cAMP and cGMP levels in neurons, improves social recognition and object memory in murine animals. Reverses anxiolytic effects induced by oxidative stress in mice by blocking cGMP-PKG signaling.</p>

<p>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.</p>

<p>MK 886 is a leukotriene antagonist that has been studied for use in treating atherosclerosis. This drug inhibits the 5-lipoxygenase activating protein thus inhibiting 5-lipoxygenase.</p>

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

<p>Inhibitor of activin receptor-like kinases (ALK4, ALK5 and ALK7), members of TGFβ type I receptor family. Blocks activin- and TGFβ-mediated signaling and phosphorylation of Smad2 downstream. Suppresses tumor-promoting and tumor-suppressing effects of TGFβ. Promotes differentiation of human embryonic stem cells (hESCs), whilst sustaining mouse ESCs in the undifferentiated state.</p>

<p>Selective inhibitor of the Src kinase family with subnanomolar IC50 values and good selectivity over c-Abl, PDGFRα and c-Kit kinases. The compound is effective in inhibiting growth in drug resistant cancer cell lines. In a recent study, it inhibited the growth of HER2-positive breast cancer cell lines which were resistant to pan-HER family kinase inhibitors such as lapatinib.</p>

<p>RET receptor tyroine kinase inhibitor</p>

<p>Rigosertib sodium is an experimental chemotherapeutic agent that is a derivative of benzyl styryl sulfone. It is synthesized chemically and functions primarily by inhibiting key signaling pathways involved in cancer cell proliferation. Specifically, Rigosertib targets the RAS signaling pathway along with the phosphatidylinositol-3-kinase/AKT and polo-like kinase 1 (Plk1) pathways, impeding the progression of the cell cycle and inducing apoptosis in malignant cells.</p>

<p>Inhibitor of cyclin-dependent kinases CDK4 and CDK6</p>

<p>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.</p>

<p>Sulindac is a non-steroidal anti-inflammatory drug that has anti-inflammatory and analgesic properties. It is used to relieve the pain of osteoarthritis and rheumatoid arthritis by reducing inflammation and inhibiting the production of prostaglandins, which are chemicals that cause inflammation.</p>

<p>Inhibits VEGFR1, VEGFR2, VEGFR3, c-kit and PDGFR tyrosine kinases</p>

<p>Inhibitor of leucine-rich repeat kinase LRRK2Â</p>

<p>Inhibitor of carbonic anhydrase; muscle relaxant</p>

<p>Lovastatin is an HMG-CoA reductase inhibitor that is used to lower LDL cholesterol levels and to aid in the management of cardiovascular diseases. Animal studies have demonstrated that this drug has vasculoprotective properties.</p>

<p>Inhibitor of LRRK2 kinase</p>

<p>Inhibitor of factor Xa</p>

<p>Inhibitor of panPI3K/mTOR</p>

<p>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.</p>

<p>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.</p>

<p>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). <br>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&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>5-Fluorouracil is a cytotoxic drug that inhibits the synthesis of DNA. It is used in combination therapy to treat cancer and is a pyrimidine analog. This drug inhibits the formation of thymidylate synthase from uracil. As a result, this leads to DNA and RNA synthesis inhibition and cell death.</p>

<p>A novel non-covalent inhibitor of the PLpro protease from SARS-CoV-2 and SARS-CoV viruses. GRL 0617 inhibits the proteolytic processing of the viral polypeptide. As PLpro also acts as a protease in pathways involved in innate immunity, there are indications that it can promote immunity against the virus.</p>

<p>Dipeptidyl peptidase 4 (DPP4) 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 tosylate 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.</p>

<p>mTOR serine/threonine kinase inhibitor</p>

<p>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.</p>