synthase inhibitors

Penicillamine (Artamine), possessing antineoplastic properties, induces apoptosis by a p53-mediated mechanism and inhibits angiogenesis by chelating with copper, a cofactor for angiogenesis. Artamine is a beta dimethyl analog of the amino acid cysteine. As a degradation product of penicillin antibiotics, Artamine chelates with heavy metals and increases their urinary excretion.

Amsilarotene (TAC101) inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer's disease (AD) treatment.

2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226/Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226/Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005). 2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226/Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226/Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2 References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005).

Benastatin A is a polyketide synthase-derived benastatin that has been found inStreptomycesand has diverse biological activities.1,2,3It inhibits glutathione S-transferase (GST; Ki= 5 μM for the rat liver enzyme).2Benastatin A is active against several bacteria, including methicillin-resistantS. aureus(MRSA; MIC = 3.12 μg/ml). It induces apoptosis and cell cycle arrest at the G1/G0phase in Colon 26 mouse colon cancer cells when used at concentrations of 20 and 16 μM, respectively.3 1.Xu, Z., Schenk, A., and Hertweck, C.Molecular analysis of the benastatin biosynthetic pathway and genetic engineering of altered fatty acid-polyketide hybridsJ. Am. Chem. Soc.129(18)6022-6030(2007) 2.Aoyagi, T., Aoyama, T., Kojima, F., et al.Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activitiesJ. Antibiot. (Tokyo)45(9)1385-1390(1992) 3.Kakizaki, I., Ookawa, K., Ishikawa, T., et al.Induction of apoptosis and cell cycle arrest in mouse colon 26 cells by benastatin AJpn. J. Cancer Res.91(11)1161-1168(2000)

Benastatin C is a polyketide synthase-derived benastatin found in [Streptomyces] with diverse biological activities. It inhibits glutathione S-transferase (GST; IC50 = 24 μg/ml for the rat liver enzyme) and the esterase activity of isolated porcine pancreatic lipase (IC50 = 10 μg/ml). Benastatin C also increases LPS- or concanavalin A-induced blastogenesis of isolated mouse spleen lymphocytes in a concentration-dependent manner.

PDMP hydrochloride is a ceramide analog originally developed as an inhibitor of glucosylceramide synthase that contains four stereoisomers due to two adjacent chiral centers, and while total PDMP hydrochloride inhibits glucosylceramide synthase by approximately 90% at 0.8 μM in MDCK cell homogenates, the inhibitory activity resides in the D-threo (1R,2R) enantiomer, which also blocks β-1,4-galactosyltransferase 6, prevents lactosylceramide-driven neuroinflammation in experimental autoimmune encephalomyelitis, additionally, PDMP hydrochloride enhances curcumin-induced antiproliferative and pro-apoptotic effects in melanoma cells.

D-threo-PPMP is a glucosylceramide (GlyCer) synthetase inhibitor.1,2It is the active enanantiomer and enzymatic inhibitory component of the racemic DL-threo-PPMP . In MDCK kidney epithelial cells, D-threo-PPMP induces a 70% reduction in cell growthin vitroat 20 μM and significantly inhibits DNA synthesis at 3 μM.3[Matreya, LLC. Catalog No. 1865] 1.Shen, W., Henry, A.G., Paumier, K.L., et al.Inhibition of glucosylceramide synthase stimulates autophagy flux in neuronsJ. Neurochem.129(5)884-894(2014) 2.Lee, L., Abe, A., and Shayman, J.A.Improved inhibitors of glucosylceramide synthaseJ. Biol. Chem.274(21)14662-14669(1999) 3.Abe, A., Inokuchi, J.-i., Jimbo, M., et al.Improved inhibitors of glucosylceramide synthaseJ. Biochem.111(2)191-196(1992)

Deoxynojirimycin (dNM) tetrabenzyl ether is an intermediate for the synthesis of glucosylceramide synthase inhibitors such as 1-dNM, a glucose analog that potently inhibits α-glucosidase I and II.

1. Corylifol A (Corylinin) displays cytotoxic activity against HepG2 and Hep3B hepatocellular carcinoma cell lines, with IC50 values of 4.6 and 13.5 ug/ml, respectively. 2. Corylifol A and Biochanin A can be the potential uncouplers of neuronal nitric oxide synthase-postsynaptic density protein-95. 3. Corylifol A and bavachin are strong inhibitors of UDP-glucuronosyltransferase 1A1 (UGT1A1) with the inhibition kinetic parameters (Ki) values lower than 1 uM.4. Corylifol A and bakuchiol are naturally occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62uM to 3.89 uM. 5. Corylifol A shows an inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells with IC50 values of 0.81 ± 0.15 uμ, it also inhibits STAT3 phosphorylation induced by IL-6 in Hep3B cells, suggests that corylifol A has antiinflammatory activity.

EGFR/HER2/TS-IN-1 are EGFR, HER2 and TS (Thymidylate synthase) inhibitors with IC50 values of 0.203, 0.088 and 0.168 μM, respectively, and have the ability to induce apoptosis (MCF7 cell death).

SMS2-IN-2 (SMS2 inhibitors) is a potent, selective and orally active sphingomyelin synthase 2 (SMS2) inhibitor, (IC50s of 100 and 56 μM for SMS2 and SMS1, respectively). SMS2-IN-2 has anti-chronic inflammatory activity.

GaMF1.39 is an antimycobacterial compound that targets the F-ATP synthase subunit γ, exhibiting enhanced anti-tuberculosis activity when used in combination with ETC inhibitors [1].

1. Desoxyrhaponticin (Deoxyrhaponticin) is an agent that is potentially effective in controlling postprandial hyperglycemia in diabetes, the in vivo antidiabetic action of this compound can be explained, in part at least, by inhibition of glucose transport in the small intestine and inhibition of glucose reabsorption in the kidney. 2. Desoxyrhaponticin and rhaponticin could be considered as promising fatty acid synthase(FAS) inhibitors, they could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells.

Desoxyrhaponticin (Standard) is a reference standard for research and analysis in studies involving Desoxyrhaponticin. 1. Desoxyrhaponticin (Deoxyrhaponticin) is an agent that is potentially effective in controlling postprandial hyperglycemia in diabetes, the in vivo antidiabetic action of this compound can be explained, in part at least, by inhibition of glucose transport in the small intestine and inhibition of glucose reabsorption in the kidney. 2. Desoxyrhaponticin and rhaponticin could be considered as promising fatty acid synthase(FAS) inhibitors, they could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells.

Albaspidin-AP, -PP, -PB inhibit Fatty acid synthase (FAS) with IC50 values ranging from 23.1+/-1.4 to 71.7+/-3.9 microM, they could be considered to be a promising class of FAS inhibitors, and FAS is emerging as a potential therapeutic target to treat can

Nitric Oxide Synthase (599-613) Blocking Peptide, Bovine Endothelial Cell (Ac-Pro-Tyr-Asn-Ser-Ser-Pro-Arg-Pro-Glu-Gln-His-Lys-Ser-Tyr-Lys-Cys) is a peptide that inhibits the function of NOSs as a result it blocks the production of NO. Because of the invol

GSK3β-peptide is a substrate mimetic peptide of glycogen synthase kinase 3-beta (GSK3-β) that binds to the active site of GSK3-β, simulating the behavior of actual substrates. It serves as a basis for developing substrate analog inhibitors of Akt, with potential applications as anticancer compounds.