Modulateurs d'enzymes

Acid α-glucosidase (83-99) (human) is derived from the exogenous enzyme which degrades glycogen, maltose and isomaltose through targeting alpha -1,4 and alpha -1,6 linkages. Once synthesised in its precursor form, within the Golgi it is glycosylated and acquires mannose 6-phosphate residues. This allows it to be transported to the Lysosome in a multistep process.Pompe disease, also known as glycogen storage disease type II, can be diagnosed through the absence of acid α-glucosidase activity within patients. Therefore glycogen degradation in the lysosome is inhibited by this autosomal recessive disorder. This results in the accumulation of glycogen and tissue destruction, hence contributing to the pathologies of muscle weakness and respiratory failure, associated with infantile onset and adult onset Pompe disease.

SIRT1 activator

Inhibitor of DDP-4 peptidase

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.

Inhibits Mer receptor tyrosine kinase (IC50 = 4.3 nM). Selective over Axl (84-fold) and Tyro3 (58-fold). UNC 2881 inhibits phosphorylation of Mer kinase in 697 B-ALL cells (IC50 = 22nM). Inhibits EGF-induced activation of a chimeric enzyme, composed of EGFR fused with Mer. Blocks collagen-mediated platelet aggregation, implying the potential of this compound for treating thrombosis.

Inhibitor of panPI3K/mTOR

Inhibitor of kinase domain of TGF-β receptor type 1

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. Zoledronic acid 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.

Inhibitor of CDK2, JAK2 and FLT3; anticancer

Inhibitor of EGFR receptor

BCR-ABL1 tyrosine kinase inhibitor

Nicotinamide phosphoribosyl transferase (NAMPT) competitive inhibitor with IC50 = 3.1 nM. A major consequence of NAMPT inhibition is the attenuation of glycolysis at the GADPH step because this enzyme requires NAD+ for activity. The compound exhibits broad spectrum anti-cancer activity and significant tumor regression was observed in vitro. Although retinal and haematological toxicity has been associated with NAMPT inhibitors, LSN 3154567 does not lead to retinopathy in rats and can be mitigated with co-administration of nicotinic acid.

Inhibitor of dihydroorotate dehydrogenase; broad spectrum antiviral

Antagonist of Aurora A serine/threonine protein kinase; antineoplastic

novel tricyclic indole; promising new treatment for a variety of diseases

Inhibitor of protein kinase PKC

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

A small molecule inhibitor with high selectivity for CDK8 over CDK19. Increases IL-10 production in stimulated human and murine macrophages and dendritic cells. Modulatory action on inflammatory responses has therapeutic potential.

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. Afatinib 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 dopamine-?-hydroxylase

Inhibitor of IGF1 receptor

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.

LY-404039 is a potent metabotropic glutamate receptor agonist with nanomolar affinity for group II receptors mGluR2 (Ki = 149 nM) and mGluR3 (Ki = 92 nM). It modulates glutamatergic activity in limbic and forebrain areas and has antipsychotic properties in animal studies. LY-404039 represents a potential new therapy for neurophysiatric disorders including schizophrenia, psychosis and anxiety.

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.

Milrinone has an application for use in the treatment of heart failure. It has been shown to increase cardiac output and decrease left ventricular end diastolic pressure (LVEDP). Milrinone also increases the amount of oxygen delivered to the tissues by increasing cardiac contractility.  Milrinone 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 Bruton's tyrosine kinase (BTK)

Inhibitor of sodium/potassium ATP-ase; anti-arrhythmic

Atorvastatin is an HMG-CoA reductase inhibitor that is used to lower lipid levels and to aid in the management of cardiovascular diseases. Animal studies have demonstrated that this drug has vasculoprotective properties. Atorvastatin calcium salt 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.

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. Pravastatin sodium salt 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.

Diclofenac is a non-steroidal anti-inflammatory drug that is used to treat the signs and symptoms of arthritis and osteoarthritis. This drug inhibits COX-1 and COX-2 enzymes. As a result, it reduces pain and inflammation in joints. Diclofenac is usually used as a first line therapy for acute and chronic pain. Diclofenac sodium salt 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.

Dual inhibitor of the adaptor protein 2-associated kinase 1 (AAK1) and BMP2-inducible kinase (BMP2K) with IC50 values of 270 nM and 1 μM, respectively. In a recent study, SGC AAK1 1 stabilised β-catenin, inhibited phosphorylation of the AP2 complex subunit mu protein (AP2M1) and activated Wnt signalling in in vitro experiments._x000D_

A pan-WNK kinase inhibitor, acting on WNK1, WNK2, WNK3, and WNK4 kinases. Affects blood pressure, heart rate, body fluid and electrolyte homeostasis in rodent models of hypertension.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) which is used to treat various types of pain and inflammation caused by arthritis. It is also a COX-2 inhibitor which reduces gastrointestinal effects of this drug. Inhibiting these enzymes, allow for a decrease in inflammatory symptoms. Meloxicam 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.

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.

Inhibitor of FLT3 kinase and acid sphingomyelinase

Dual IGF-1R and InsR kinase inhibitor; antineoplastic

Competitive, reversible inhibitor of α-glucosidases used for the control of postprandial hyperglycaemia in patients with type 2 diabetes mellitus. It inhibits digestive enzymes with α-glucosidase activity, which breakdown complex sugars to absorbable monosaccharides. It also reduces the levels of glycated haemoglobin (HbA1c).

Anti-parasitic; pyruvate ferredoxin oxidoreductase inhibitor

Orally available prodrug of gemcitabine

MGMT, known as O6-methylguanine-DNA methyltransferase, is a DNA repair enzyme that plays an important role in chemoresistance to alkylating agents. MGMT repairs the toxic DNA O6-Methylguanine lesion caused by Temozolomide (TMZ), an oral alkylating agent used for the treatment of glioblastoma. MGMT repairs damaged guanine nucleotides by transferring the methyl at O6 site of guanine to its cysteine residues, thus avoiding gene mutation, cell death and tumorigenesis. The expression of MGMT gene is mainly regulated by epigenetic modification. Loss of MGMT expression is due to methylation of the CpG island of MGMT promoter.

O8 OGG1 Inhibitor is a glycosylase enzyme that catalyses the conversion of guanine to xanthine. It is a key enzyme in the DNA repair mechanism called base excision repair or BER. This enzyme inhibits the hydrolysis of glycosidic bond required for the excision of 8-oxoguanine from double stranded DNA, which leads to accumulation of mutations. Additionally, it has been proposed as monotherapy for certain types of cancers. Furthermore, it has been seen to sensitise tumours for chemotherapy therefore research is being carried out to identify its potential to be used alongside cancer therapy. O8 OGG1 Inhibitor 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 poly (ADP-ribose) polymerase enzyme; antineoplastic

EGFR tyrosine kinase inhibitor

A potent non ATP-competitive inhibitor of MAP/ERK kinase (MEK). Has anti-tumor activity in melanoma and papillary thyroid cancer cells with B-Raf mutations. Enhances generation and survival of induced pluripotent stem cells (iPSCs).

A potent inhibitor of histone deacetylases (HDACs) of class I and II with anti-tumoral activity. The compound blocks HDAC catalytic activity by chelating zinc ion in the enzyme’s active site. Extensively used in research as epigenetic modifier able to block cell growth and downregulate proliferation-associated factors. It has also been reported that trichostatin A induces apoptosis via a histone-modification independent mechanism in oral squamous cell carcinoma cell lines. Initially discovered as anti-fungal compound from Streptomyces hygroscopicus for the control of fungal infections caused by the genus Trichophyton.

Activator of soluble guanylyl cyclase (sGC) which stimulates cGMP production and is effective in cells under oxidative stress. Ataciguat stimulates the heme-free form of the sGC enzyme via the sGC N-terminus of β1-subunit. Ataciguat can promote vasorelaxation and hypotension by restoring or potentiating the nitric oxide (NO) signalling pathway.

Amino acids 487-496 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 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.

Inhibitor of ErbB2 (IC50 = 3 nM) and EGFR kinase (IC50 = 6.4 nM) with anti-proliferative effects. It inhibits ErbB2 receptor autophosphorylation and induces G1 cell cycle block. The CP 724714 treatment induces reduction of downstream ErbB2 receptor tyrosine kinase signalling, tumor cell apoptosis, release of caspase 3 and regression of tumors in in vivo and in vitro models.

Monoamine oxidase-B inhibitor; anti-parkinsonian; neuroprotective

Inhibitor of the Bruton tyrosine kinase