Enzyme Modulators

<p>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.</p>

<p>Selective inhibitor of the transforming growth factor beta receptor TGFβ1. RepSox can replace Sox, a transcriptional factor required for cell self-renewal, in reprogramming of adult cells to induced pluripotent stem cells (iPSCs). In the cloned interspecies embryos, RepSox induced expression of pluripotency regulatory genes Oct4 and Nanog, improved viability and developmental potential of embryos in the pre-implantation stage.</p>

<p>γ-secretase inhibitor; inhibits notch signaling</p>

<p>Indomethacin is a nonsteroidal anti-inflammatory drug that inhibits the production of prostaglandin PGE2. It is used to treat pain, fever, and inflammation. Indomethacin's mechanism of action is not well understood, but it may be due to interference with the ability of PMNs to bind to the surface of bacteria or to release reactive oxygen species. The drug has been shown to reduce mitochondrial membrane potential in mammalian cells, leading to apoptosis. This effect on mitochondria may also contribute to Indomethacin's anti-inflammatory effects. Indomethacin 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>Roflumilast is a selective phosphodiesterase-4 inhibitor that is used for the treatment of exacerbations in patients with chronic obstructive pulmonary disease (COPD). It is also used to treat plaque psoriasis. This drug has anti-inflammatory and immunomodulatory effects as it aids in increasing levels of cAMP.</p>

<p>Inhibitor of vacuolar-type proton pump</p>

<p>Potent and specific inhibitor of the tyrosine protein kinase Mer precursor (MERTK) with 38-fold selectivity over the FMS-like protein kinase FLT3. UNC 4203 inhibits MERTK with an IC50 value of 2.4 nM and shows favourable pharmacokinetic properties. In vivo experiments in mice showed that UNC 4203 dramatically decreased the phosphorylation of MERTK in bone marrow leukemia cells.</p>

<p>Nilotinib is a kinase inhibitor that is used for the treatment of Chronic Myeloid Leukemia (CML). This drug is also used for the treatment of CML that is resistant to imatinib. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. It also inhibits PDGFR and c-kit.</p>

<p>Inhibits JAK1 and JAK2 kinases</p>

<p>Toceranib phosphate is a receptor tyrosine kinase inhibitor. Toceranib phosphate has been shown to be effective in the treatment of skin cancer and other types of cancer, including lung cancer and breast cancer. It is approved in the US as a treatment for canine mastocytoma (mast cell tumours).</p>

<p>Nabumetone is a non-steroidal anti-inflammatory drug that is used in the treatment of osteoarthritis and rheumatoid arthritis. This drug is also a cyclooxygenase inhibitor and works by inhibiting this enzyme so that pain and inflammation is reduced.</p>

<p>Camostat is a serine protease inhibitor that is used for the treatment of chronic pancreatitis. This drug has shown to reduce inflammation and pain. Studies have shown that Camostat has also inhibited the entry of SARS-CoV-2 in lung cells by inhibiting the priming process of S-protein, necessary for the viral entry into host cells.</p>

<p>Bruton's tyrosine kinase antagonist; reduces Fcγ receptor signaling</p>

<p>Pan-class I phosphatidylinositide 3-kinase (PI3K) inhibitor (IC50 = 3, 33, 3 and 75 nM at catalytic subunits p110α, p110β, p110δ and p110γ respectively). Inhibits proliferation in several cancer cell lines, such as glioblastoma, breast and prostate cancer cells. Has synergistic anti-cancer effect in combination with MEK/ERK kinase inhibitor GDC-0973 (cobimetinib).</p>

<p>Irsogladine is a gastroprotective drug that is used for the treatment of GERD and gastric ulcers. This drug also has antioxidant properties. Irsogladine is a phosphodiesterase-4 inhibitor and increases levels of cAMP. It helps to prevent and heal damage to the stomach lining.</p>

<p>Acetylcholinesterase inhibitor; therapy for Alzheimer's disease</p>

<p>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.</p>

<p>GC 376 is an inhibitor of the main protease Mpro (3CLpro) in coronaviruses as well as picornaviruses. This broad-spectrum antiviral compound has been used as investigational veterinary drug for treatment of feline infectious peritonitis virus (FIPV) infections. Recent studies also showed that GC 376 inhibits the main protease Mpro (3CLpro) from SARS-CoV-2 with IC50 of 0.03 μM and EC50 of 3.37 μM.</p>

<p>Potent agonist of a1β1γ1 5′-adenosine monophosphate-activated protein kinase (AMPK). It binds to the allosteric drug and metabolite (ADaM) site at the α- and β- subunit interface of AMPK. It has potential for the treatment of diabetic nephropathy. PF 06409577 reduces infections caused by flaviviruses, mediated by changes in the metabolism of lipids in host cells.</p>

<p>Selective c-Met kinase inhibitor</p>