Enzyme Modulators

<p>Potent, selective and cell-permeable tool for modulation of O-GlcNAcylation. Ac4GlcNAcF3 is a dual modulator of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ac4GlcNAcF3 perturbates the GlcNAc cycling as OGT can incorporate GlcNAcF3 onto proteins but subsequently, it cannot be removed by OGA. In a mouse embryogenic fibroblast cell line, Ac4GlcNAcF3 increased the level of protein O-GlcNAcylation.</p>

<p>A prodrug of the DNA-intercalating agent daunorubicin with anti-tumoral activity, used for suicide gene therapy and activity-dependent ablation of cells. Daun02 is an inactive form of the toxin, which gets activated upon cleavage with prodrug-activating enzyme β-galactosidase, yielding daunorubicin. Genetic constructs have been designed carrying the lacZ gene, coding for β-galactosidase, under control of application-specific promoters. The cells expressing the β-gal undergo cell death since the enzyme hydrolizes the prodrug into the active toxin.</p>

<p>Sildenafil is a potent inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), consequently preventing the degradation of cGMP in the smooth muscle cells of the pulmonary vasculature and penis. For this reason Sildenafil can be used to increase blood flow, decrease inflammation and mucus production in the lungs and also can be used in the treatment of erectile dysfunction in men. This is largely due to the increased availability of cGMP which can cause the relaxation of the smooth muscles to be prolonged.</p>

<p>Selective and reversible inhibitor of the multicatalytic 26S proteasome. The inhibition of protein breakdown affects several metabolic pathways and leads to cell death. The compound is effective in treating multiple myeloma because it prevents the binding of myeloma cells to bone marrow stroma and inhibits osteoclast differentiation.</p>

<p>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.</p>

<p>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.</p>

<p>Cyclooxygenase inhibitor; anti-inflammatory; antipyretic; analgesic</p>

<p>Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) that has been used to treat pain and inflammation. Ketoprofen inhibits the production of inflammatory prostaglandins, which are released by platelets in response to injury or infection. The main mechanism of action is inhibition of cyclooxygenase enzymes COX 1 and COX 2 at the level of transcriptional activation. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation.</p>

<p>PI3K/mTOR kinase inhibitor; anti-neoplastic</p>

<p>Neratinib is a protein kinase inhibitor that is used in the treatment of breast cancer. This drug binds to and inhibits EGFR, HER2 and HER4. As a result of this, it prevents autophosphorylation of tyrosine residues and reduces oncogenic signalling.</p>

<p>Inhibitor of FGFR kinase</p>

<p>Aurora kinase inhibitor</p>

<p>Activator of SIRT1 deacetylase</p>

<p>Inhibitor of cyclin dependend kinases</p>

<p>HMG-CoA reductase inhibitor</p>

<p>A potent and selective agonist of CCR4 chemokine receptor with IC50 values ranging from 10 to 25 nM across different species. CCR4 is involved in activation and migration of Th2 lymphocytes to the lungs in response to allergens. Treating sensitised rats results in reduced inflammation of lung tissue.</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 tosylate also has the potential for drug interactions with other drugs that are metabolized by cytochrome P450 enzymes.<br>Sorafenib tosylate 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>CBP/p300 histone acetyltransferase activator</p>

<p>EGFR tyrosine kinase inhibitor</p>

<p>Inhibits Wnt signaling pathway by targeting porcupine, a membrane-bound O-acyltransferase involved in the palmitoylation and secretion of Wnt. Anti-cancer properties of LGK 974 have been demonstrated in various tumor models of breast cancer, head and neck squamous cell carcinoma and glioblastoma. Blocks LPS-mediated inflammatory response in epithelial and endothelial cells.</p>