Enzyme Modulators

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.

TDZD 8 is a selective, non-ATP competitive inhibitor of the glycogen synthase kinase GSK3β. TDZD 8 inhibits GSK3β with IC50 of 2 μM and was reported to not significantly affect Cdk-1/cyclin B, casein kinase CK-II, protein kinase A and C (PKA, PKC) activities. TDZD 8 was also identified as an inhibitor of the main protease in coronaviruses. In an in vitro study, TDZD 8 was characterised as an aggregate-based inhibitor as the presence of Triton-X decreased the inhibitory potency to Mpro protease of the SARS-CoV-2 virus (IC50 without Triton-X: 2.15 μM).

Cilastatin is a renal dehydropeptidase inhibitor drug that is used to prevent degradation of imipenem. It is used to treat a variety of infections in combination with imipenem. This drug blocks the mechanism of imipenem which is hydrolyzed by dehydropeptidase-I. Cilastatin sodium 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.

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. Crizotinib 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.

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. BAY 73-6691 has been studied as a potential therapy for Alzheimer’s disease.

Inhibitor of proteaseγ‐secretase, which allows to modulate of the activity of γ‐secretase substrates Notch, E-cadherin, ErbB4, and amyloid precursor protein (APP). The compound can inhibit the growth of tongue carcinoma cells by arresting cell cycle in G0-G1 phase, modulate the activity of Notch1 receptor and Caspase-3 protease and induce apoptosis. It was also demonstrated that this inhibitor reduces the levels of β-amyloid peptide in the brain of mice model for Alzheimer’s disease. This compound also enhances the neuronal differentiation embryonic cells.

Potent inhibitor of β5i subunit of immunoproteasomes (IC50 = 6.6 nM), selective over β5c subunit (IC50 = 287 nM). The β5i subunit of immunoproteasomes (iCPs) is the chymotrypsin-like active sites that have implications on anti-cancer affects. On the other hand, β5c subunits are found in constitutive proteasomes (cCPs).

Aminopterin is an antineoplastic agent and antifolate, which is a synthetic derivative of pteroylglutamic acid. It functions as a chemotherapeutic agent by inhibiting dihydrofolate reductase, an enzyme crucial in the folic acid pathway, thereby preventing the conversion of dihydrofolate to tetrahydrofolate. This disruption leads to impaired synthesis of purine nucleotides and thymidylate, which are essential for DNA synthesis and cell division. Aminopterin is primarily used in cancer research and treatment due to its ability to halt the proliferation of rapidly dividing cells. It has historical significance as one of the initial antifolates developed and was utilized in the treatment of leukemia and other malignancies. However, due to its toxic side effects and the development of safer folate antagonists like methotrexate, its clinical use has been limited. Today, aminopterin's role is more focused within research settings, contributing to the understanding of cell biology and cancer pathways.

Olaparib is a small molecule inhibitor of DNA polymerase and topoisomerase, which are enzymes that maintain the integrity of DNA. Olaparib inhibits the proliferation of cancer cells by preventing the synthesis of DNA, RNA, and proteins. Olaparib has been shown to be effective against breast cancer tissues in mouse models. It also has minimal toxicity in humans and has been shown to inhibit the growth of diseased cells with significant cytotoxicity. Olaparib 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.

Iproniazid is an irreversible monoamine oxidase inhibitor of the hydrazine class. It was initially used for the treatment of tuberculosis however now it is used for the treatment of depression. Iproniazid inhibits the activity of monoamine oxidases (MAOs) by itself and through an active metabolite, isopropylhydrazine. Additionally, it prevents the enzymatic breakdown of norepinephrine. Iproniazid 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.

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.

SD 0006 is a small-molecule inhibitor, which is synthesized through specialized chemical processes. It functions by selectively inhibiting the cyclooxygenase-2 (COX-2) enzyme, which plays a significant role in the inflammatory pathway. This inhibition reduces the production of pro-inflammatory prostaglandins, ultimately leading to a decrease in inflammation. In scientific research, SD 0006 is primarily utilized in the study of inflammation-related diseases. It serves as a valuable tool in elucidating the pathways and physiological mechanisms involved in diseases such as rheumatoid arthritis, osteoarthritis, and other inflammatory conditions. By targeting COX-2, SD 0006 helps to understand the differential effects of COX inhibition and the balance between therapeutic efficacy and potential side effects. Its applications extend to in vitro cellular assays as well as in vivo animal models, providing insights into the development of new anti-inflammatory therapeutics. The specificity and mode of action of SD 0006 make it an essential component in both pharmacological studies and the broader field of biomedical research.

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.

Rensocatib is a reversible inhibitor of DPP-1, also known as cathepsin C, which is a peptidase involved in the activation of neutrophil, an elastase-like serine protease in lung tissue. Brensocatib is an oral drug used to treat infections of the airways (lungs) that are characterised by a permanent enlargement and presenting symptoms such as, coughing and greater mucus production (bronchiectasis). Alternative names of brensocatib are INS-1007 and AZD7986.

Inhibitor of MEK kinase

H+/K+ ATPase inhibitor

Inhibitor of Factor Xa; anti-thrombotic

Baricitinib is a Janus kinase inhibitor (JAK) currently used as monotherapy in the treatment of rheumatoid arthritis. Barictinib is also recommened for the treatment of atopic dermatitis and systemic lupus erythematosus. In mice interestingly, the administration of baricitinib reduced the inflammatory effects induced by a high-sugar diet on the metabolism.

Cilastatin is a renal dehydropeptidase inhibitor, which is a compound sourced from synthetic processes designed to augment the pharmacokinetic profile of certain beta-lactam antibiotics. Its primary mode of action is to inhibit the enzyme dehydropeptidase I (DHP-I), located in the renal brush border. This enzyme typically degrades antibiotics, like imipenem, within the renal tubules. By inhibiting DHP-I, cilastatin prevents the inactivation of these antibiotics, thereby prolonging their active presence in the body and enhancing their antimicrobial efficacy. The key application of Cilastatin is in combination with the antibiotic imipenem, forming a synergistic therapeutic approach to treat severe bacterial infections. The pair, imipenem-cilastatin, is particularly effective against a wide range of Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Importantly, Cilastatin itself has no inherent antibacterial activity; its value lies solely in its ability to protect imipenem from renal degradation, ensuring optimal therapeutic concentrations are maintained during the treatment of complex infections.

Inhibitor of GSK3 kinase; activator of Wnt signalling

Fasudil hydrochloride is a Rho-kinase inhibitor, which is a synthetic compound derived from natural sources, primarily used in scientific research. The mode of action of Fasudil hydrochloride involves the inhibition of Rho-associated protein kinase (ROCK), a crucial player in the regulation of the actin cytoskeleton. By inhibiting ROCK, Fasudil alters various cellular functions, including contraction, motility, proliferation, and apoptosis. Fasudil hydrochloride is primarily applied in neurological and cardiovascular research. It is utilized to investigate the therapeutic potential for conditions like cerebral vasospasm, ischemic stroke, and other vascular disorders. In the realm of neuroscience, it aids in studying the pathophysiological processes of neurodegenerative diseases, given its capacity to ameliorate the effects of vascular damage and enhance blood flow. Additionally, its role is being explored in areas related to hypertension and atherosclerosis. The broad applicability of Fasudil hydrochloride in diverse research areas accentuates its significance in understanding disease mechanisms and evaluating potential therapeutic interventions.

This product 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.

First generation PI 3-kinase inhibitor

Inhibitor of DNA topoisomerase I

Inhibitor of cGMP-dependent phosphodiesterase 2A (PDE2A) with IC50 = 2 nM and has higher affinity over other phosphodiesterases (> 500-fold). Increases cGMP in rodent brain in vivo. Reverses anxiolytic behaviour, enhances performance of new object recognition and social recognition tasks.  Potentiates NMDA signalling and reverses behavioural effects of NMDA antagonists.

NMDA receptor antagonist

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.

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.

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

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).

Inhibitor of IKKβ serine kinase

Inhibitor of calpain, a calcium-dependent cysteine protease which is implicated in the apoptosis as well as in synaptic plasticity, where it was seen to block long-term potentiation. Calpain inhibitor II has also antiviral properties as it was shown to inhibit the main protease Mpro (3CLpro) from SARS-CoV-2 with IC50 of 0.97 μM.

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.

Inhibitor of cyclin dependend kinases

Lysine-specific demethylase 1 ( LSD1) antagonist

Irreversible blocker of three members of the ErbB family (ErbB1, ErbB2/HER2, and ErbB4) with IC50 in nanomolar range. The compound binds covalently to cysteine 797 residue in HER2 and blocks downstream cellular signalling, inhibits cellular growth and promotes apoptosis. Afatinib has been used for the treatment of tyrosine kinase inhibitor-resistant tumours with mutations in ErbB genes, especially for deletions in exon 19 and single nucleotide substitutions in exon 21. It has been used for treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, colorectal cancer, etc.

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

Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic

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 >85% of the PARP activity in cellular systems.

Inhibits Jak kinases; immunosuppressive; anti-inflammatory

Synthetic phosphodiesterase inhibitor

A specific inhibitor of Bone Morphogenetic Protein (BMP) type 1 receptors ALK2 and ALK3 (IC50  < 0.5 µM). Dorsomorphin analog that exclusively targets the BMP but not VEGF signaling. It is able to inhibit the BMP-induced Smad1/5/8 activation but not the p38/MAP kinase signaling or Activin A-induced Smad2 activation.

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. The mode of action of MLN 4924 makes it a critical compound in cancer research as its inhibition of cullin-RING ligase (CRL) ubiquitin ligases places a halt on the degradation of tumor suppressor proteins. This has potential therapeutic implications in oncology, particularly for targeting tumor progression and survival in cancer cells. Studies have shown its efficacy in a variety of malignancies, providing a promising avenue for novel cancer therapies. As an experimental drug, it is primarily utilized within preclinical and early-phase clinical trials to assess its safety and effectiveness in treating different cancer types.

Small molecule antagonist of heparan sulfate that binds to glycosaminoglycans electrostatically. Surfen neutralised anti-coagulant activity of unfractionated and low molecular weight heparins, inhibited enzymatic sulfation and degradation reactions. Surfen also blocked signalling and cell adhesion to fibronectin that was triggered by heparan sulphate.

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. Kifunensine 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 dioxygenase IDO1

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.  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&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 guanylyl cyclase

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.

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.