Modulateurs d'enzymes

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. 6-Thioguanine 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.

Selective inhibitor of the interaction between the UNC119 chaperone and its cargo. Squarunkin A inhibits activation of Src kinase by interrupting the interaction between the myristoylated peptide at the N-terminus of the Src kinase and UNC119A chaperone (IC50 = 10 nM). Squarunkin A impairs the UNC119-mediated enrichment of plasma membrane with non-receptor protein tyrosine kinase Src, resulting in the decrease in Src autophosphorylation and decreased oncogenic Src signalling.

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. Apixaban 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.

p38 MAP kinase antagonist

Inhibits phorbol ester TPA/PMA; immunosuppressant

Inhibitor of carbonic anhydrase; muscle relaxant

Hydroxychloroquine is a drug that is used to treat multiple types of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and discoid lupus. It is a prodrug, which is activated in the liver to hydroxychloroquine. It inhibits the production of inflammatory cytokines and nitric oxide by binding to the toll-like receptor 4 (TLR4) and inhibiting signaling pathways downstream of TLR4 activation. Additionally, Hydroxychloroquine is used to prevent and treat malaria caused by parasitic protozoan from the Plasmodium genus. Furthermore, recent studies revealed that hydroxychloroquine has beneficial effects on COVID-19 patients, as the current evidence shows that hydroxychloroquine inhibits SARS CoV-2 entry in host cells by interfering with endocytosis and affecting the glycoprofile on the spike glycoprotein. Hydroxychloroquine sulfate 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 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.

Inhibits JAK1 and JAK2 kinases

Potent and irreversible inhibitor of phosphoinositide-3-kinase (PtdIns-3-kinase) with IC50 of 0.1 nM. PX 866 inhibited cell motility and growth of 3D spheroids of glioblastoma, breast, prostate and colon cancer cell lines at low nanomolar concentrations. PX 866 also exhibited anti-tumoral activity in vivo in xenograft models for ovarian and lung cancer.

Reversible inhibitor of trypsin

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.

Pritelivir mesylate is an antiviral compound, which is derived from thiazolylamide class molecules, with a targeted mechanism of action against the herpes simplex virus (HSV). It functions by inhibiting the viral helicase-primase complex, which is essential for the replication of viral DNA. This distinct mode of action differentiates it from traditional treatments like acyclovir, which targets viral DNA polymerase. Pritelivir mesylate is primarily used in the treatment and suppression of HSV infections, including HSV-1 and HSV-2. By targeting the helicase-primase, it effectively reduces the replication of the virus, leading to decreased viral shedding and lesion formation. Its unique pathway offers an alternative for cases where resistance to standard antivirals occurs. Given its potential, Pritelivir mesylate is under extensive study to better understand its efficacy and safety profile. Its promising results in early clinical trials may provide a significant advancement in antiviral therapies, offering new hope for managing and controlling HSV infections.

Teniposide is a cytotoxic drug that is used in the treatment of refractory childhood acute lymphoblastic leukemia. It has antitumour activity. It is a type II topoisomerase inhibitor. This drug inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. Teniposide 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.

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.

Inhibitor of VEGFR, PDGR, c-Kit and Ret; inhibitor of angiogenesis

SU 3327, originally introduced as a thiadiazole JNK inhibitor (De et al. 2009) has recently been identified as having antibiotic activity against a broad range of bacteria including drug-resistant gram positive and negative strains (Strokes et al. 2020). This molecule has been given the fictional name ‘Halicin’ inspired by the AI approach used to discover its novel biological activity.

Mirodenafil dihydrochloride is a potent phosphodiesterase-5 (PDE5) inhibitor, which is a synthetic compound with a primarily chemical origin. Its mode of action involves the inhibition of the enzyme PDE5, which predominantly resides in the smooth muscle cells lining blood vessels. By inhibiting PDE5, Mirodenafil dihydrochloride effectively increases the levels of cyclic guanosine monophosphate (cGMP), leading to the relaxation of smooth muscle tissues and vasodilation. This mechanism of action makes Mirodenafil dihydrochloride particularly effective in the treatment of erectile dysfunction (ED). By enhancing blood flow to specific areas of the body, primarily the corpus cavernosum of the penis, it facilitates the achievement and maintenance of an erection in response to sexual stimulation. The compound’s selectivity for PDE5 over other phosphodiesterases minimizes potential side effects and enhances its therapeutic efficacy. As such, Mirodenafil dihydrochloride serves as a valuable tool in clinical settings for managing erectile dysfunction, providing an alternative for patients who may not respond to or tolerate other PDE5 inhibitors.

Inhibitor of BACE1 protease

Anagrelide is a thrombocytopenic drug that is used to treat thrombocythemia and related conditions. This drug works by decreasing the platelet count by suppressing transcription factors that are necessary for the maturation of platelets. This drug is also a phosphodiesterase III inhibitor. Anagrelide HCl 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.

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.

Proteosome inhibitor; pro-apoptotic; has anti-myeloma activity

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.

Drotaverine is an antispasmodic drug that is used to alleviate gastrointestinal and genitourinary smooth muscle spasms. This drug works by inhibiting phosphodiesterase-4 and increasing levels of cAMP leading to smooth muscle relaxation. Drotaverine HCl 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.

Tacrolimus is a calcineurin inhibitor drug that is used for the prevention of rejection after an organ transplant. This drug can also be used in the treatment of severe atopic dermatitis. Tacrolimus’ mechanism of action is not well known however it is understood that this drug inhibits T-lymphocyte activation by binding to an intracellular protein called FKBP-12. This drug also has anti-inflammatory properties. Tacrolimus monohydrate 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.

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

Ligand of plasminogen; used for bleeding control

Inhibitor of Aurora kinases A, B and C

Inhibits human and mouse diacylglycerol O-acyltransferase 1 (DGAT-1) with IC50 values of 9 and 22 nM, respectively. Selective for DGAT-1 over DGAT-2 (IC50 = 53 µM), acyl coenzyme A transferase (IC50 = 296 µM) and other acyltransferases. Reduces plasma and liver triglycerides, FFA, chylomicron secretion and increases HDL cholesterol in vivo.

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.

Odevixibat is a pharmacological agent that functions as an ileal bile acid transport inhibitor, which is synthesized through complex organic chemistry methods to create a specific molecular structure targeting bile acid transport mechanisms. It works by inhibiting the apical sodium-dependent bile acid transporter (ASBT) in the terminal ileum. This action reduces the reabsorption of bile acids from the small intestine back into the liver, thereby reducing overall bile acid levels in the body. The primary application of Odevixibat is in managing progressive familial intrahepatic cholestasis (PFIC), a rare genetic disorder characterized by impaired bile flow and accumulation of bile acids, leading to liver injury. By lowering bile acid levels, Odevixibat can alleviate symptoms such as intense pruritus and slow the progression of liver damage. Its role in improving patient outcomes in cholestatic liver diseases makes it a key therapeutic option under investigation and application. Additionally, its unique mechanism of action provides a valuable approach to addressing unmet medical needs in rare hepatic conditions.

H-9 hydrochloride is a group P2 proton pump inhibitor that inhibits the H+/K+ ATPase enzyme. It is a prodrug that is metabolized to the active form, H-9, by esterases in the gut wall. The proton pump inhibitor blocks the conversion of K+ to H+, thereby reducing gastric acidity. H-9 hydrochloride has been shown to have antimicrobial activity and has been used in the treatment of infectious diseases such as bowel disease and inflammatory bowel disease. The drug also has kinetic energy which can be measured using laser ablation and X-ray diffraction data.

Inhibits Akt translocation by targeting the pleckstrin homology (PH) domain. Inhibits hepatitis C virus NS5B RNA-dependent RNA polymerase (IC50 = 79 µM). Attenuates cannabinoid agonist-mediated proliferation of neural stem/precursor cells.

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

Nimesulide is a non-steroidal anti-inflammatory drug that is used to treat acute pain and primary dysmenorrhea. This drug is also a cyclooxygenase inhibitor and works by targeting a range of key mediators of the inflammatory process such as histamines and free radicals to reduce pain and inflammation. Nimesulide 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.

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

Cyclooxygenase inhibitor; anti-inflammatory; antipyretic; analgesic

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

Cyclosporin B is an antifungal and immunosuppressive cyclic peptide, which is derived from the fungus *Tolypocladium inflatum*. The compound is a member of the cyclosporin family, characterized by cyclic polypeptides with a unique arrangement of amino acids that enable its biological activity. Though its precise mode of action is not completely delineated, it is observed to influence cell growth and viability by potentially disrupting cellular communication or signal transduction pathways. Cyclosporin B is primarily used in scientific research due to its complex interactions with cellular processes, offering insights into fungal growth mechanisms and immune modulation. While it is not as commonly applied as Cyclosporin A in therapeutic contexts, its distinctive bioactivity makes it a subject of interest for studies in pharmacology and toxicology. Researchers explore its potential applications in discovering novel antifungal strategies and understanding immune response pathways.

An inhibitor of caspase-1 and active metabolite of VX-765. Blocks lipopolysaccharide-mediated release of cytokines. Suppresses release of interleukins IL-1β and IL-18. Reduced inflammatory cytokines, such as IL-1α, tumor necrosis factor-α, IL-6 and IL-8, observed in in vivo models of rheumatoid arthritis and skin inflammation.

Inhibitor of ataxia telangiectasia mutated (ATM) kinase and AKT kinase with anti-cancer activity. ATM is a nuclear protein kinase and a signal transducer sensing DNA damage as well as controlling double strand DNA break (DSB) repair. It is a radiotherapy and chemotherapy sensitizer, especially in tumors sensitive to DNA alkylating agents (such as temozolomide). Moreover, KU 55933 inhibits phosphorylation of cytoplasmic AKT kinase, downregulates synthesis of cyclin D1 and induces cell cycle arrest in G1 phase.

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.

Inhibitor of COX-1 and COX-2 cyclooxygenases

Inhibitor of protein kinase CK2

Inhibits RNAPII-mediated trasncription; immunosuppressant; anti-inflammatory

A potent selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE-5), thereby reducing the degradation rate of cGMP. Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension. Sildenafil citrate 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.

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

BRK tyrosine kinase (PTK6) inhibitor; anti-proliferative in breast cancer cells

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.

Proteosome inhibitor; antineoplastic