WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201266
Description: Entinostat, also known as MS-275 or SNDX-275, is a potent HDAC inhibitor with potential antineoplastic activity. Entinostat binds to and inhibits histone deacetylase, an enzyme that regulates chromatin structure and gene transcription. This agent appears to exert dose-dependent effects in human leukemia cells including cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations; a marked induction of reactive oxygen species (ROS); mitochondrial damage; caspase activation; and, at higher concentrations, apoptosis.
MedKoo Cat#: 201266
Chemical Formula: C21H20N4O3
Exact Mass: 376.15354
Molecular Weight: 376.41
Elemental Analysis: C, 67.01; H, 5.36; N, 14.88; O, 12.75
Synonym: MS275; MS-275; MS 2275; SNDX275; SNDX-275; SNDX 275; Entinostat
IUPAC/Chemical Name: pyridin-3-ylmethyl 4-((2-aminophenyl)carbamoyl)benzylcarbamate.
InChi Key: INVTYAOGFAGBOE-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26)
SMILES Code: O=C(OCC1=CC=CN=C1)NCC2=CC=C(C(NC3=CC=CC=C3N)=O)C=C2
Entinostat inhibits class I HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM, respectively. Entinostat preferentially inhibits cell proliferation/survival and inactivates downstream signaling in erbB2-overexpressing compared with basal breast cancer cells. Entinostat reduces the levels of both erbB2 and erbB3, as well as significantly decreases P-erbB2, P-erbB3, P-Akt, and P-MAPK in erbB2-overexpressing cells. Additionally, Entinostat promotes apoptosis and induces cell cycle arrest predominantly at G(1) phase in erbB2-overexpressing cells, whereas Entinostat mainly induces G(2)-M arrest in basal breast cancer cells. The cellular bias of Entinostat is shown to be related partly to the levels of erbB3 expression that directly impact the ability of Entinostat to inhibit proliferation/survival of the erbB2-overexpressing breast cancer cells. These findings show that Entinostat may be developed as a novel therapeutic agent to treat breast cancers with coexpression of both erbB2 and erbB3. see http://www.ncbi.nlm.nih.gov/pubmed/19826038.
Entinostat is an orally bioavailable, selective, class I histone deacetylase (HDAC) inhibitor. Entinostat is currently being investigated in randomized, Phase 2 clinical studies in combination with the aromatase inhibitor, exemestane, for the treatment of metastatic or locally advanced ER+ breast cancer; in combination with erlotinib in advanced non-small-cell lung cancer, and in combination with azacitidine in myelodysplastic syndrome. Phase 2 single arm studies in non-small cell lung cancer and colorectal cancer, also are being conducted in combination with azacitidine; and a Phase 2 in Hodgkin's lymphoma is ongoing with single agent entinostat. Entinostat's long half-life allows for weekly or every-other-week oral dosing.
1: Schech AJ, Shah P, Yu S, Sabnis GJ, Goloubeva O, Rosenblatt P, Kazi A, Chumsri S, Brodie A. Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer. Breast Cancer Res Treat. 2015 Jul 2. [Epub ahead of print] PubMed PMID: 26133921.
2: Ruiz R, Raez LE, Rolfo C. Entinostat (SNDX-275) for the treatment of non-small cell lung cancer. Expert Opin Investig Drugs. 2015 Aug;24(8):1101-9. doi: 10.1517/13543784.2015.1056779. Epub 2015 Jun 22. PubMed PMID: 26098363.
3: Schech A, Kazi A, Yu S, Shah P, Sabnis G. Histone Deacetylase Inhibitor Entinostat Inhibits Tumor-Initiating Cells in Triple-Negative Breast Cancer Cells. Mol Cancer Ther. 2015 Jun 2. [Epub ahead of print] PubMed PMID: 26037781.
4: Frys S, Simons Z, Hu Q, Barth MJ, Gu JJ, Mavis C, Skitzki J, Song L, Czuczman MS, Hernandez-Ilizaliturri FJ. Entinostat, a novel histone deacetylase inhibitor is active in B-cell lymphoma and enhances the anti-tumour activity of rituximab and chemotherapy agents. Br J Haematol. 2015 May;169(4):506-19. doi: 10.1111/bjh.13318. Epub 2015 Feb 23. PubMed PMID: 25712263.
5: Vendetti FP, Topper M, Huang P, Dobromilskaya I, Easwaran H, Wrangle J, Baylin SB, Poirier JT, Rudin CM. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget. 2015 Jan 1;6(1):56-70. PubMed PMID: 25474141; PubMed Central PMCID: PMC4381578.
6: Ngamphaiboon N, Dy GK, Ma WW, Zhao Y, Reungwetwattana T, DePaolo D, Ding Y, Brady W, Fetterly G, Adjei AA. A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors. Invest New Drugs. 2015 Feb;33(1):225-32. doi: 10.1007/s10637-014-0174-6. Epub 2014 Nov 5. PubMed PMID: 25371323.
7: Lee J, Bartholomeusz C, Mansour O, Humphries J, Hortobagyi GN, Ordentlich P, Ueno NT. A class I histone deacetylase inhibitor, entinostat, enhances lapatinib efficacy in HER2-overexpressing breast cancer cells through FOXO3-mediated Bim1 expression. Breast Cancer Res Treat. 2014 Jul;146(2):259-72. doi: 10.1007/s10549-014-3014-7. Epub 2014 Jun 12. PubMed PMID: 24916181; PubMed Central PMCID: PMC4119423.
8: Yang X, Zhang Q, Chen M, Hu L. Pharmacokinetic interaction of entinostat and lapatinib following single and co-oral administration in rats. Xenobiotica. 2014 Nov;44(11):1009-13. doi: 10.3109/00498254.2014.919431. Epub 2014 May 16. PubMed PMID: 24831712.
9: Tellez CS, Grimes MJ, Picchi MA, Liu Y, March TH, Reed MD, Oganesian A, Taverna P, Belinsky SA. SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome. Int J Cancer. 2014 Nov 1;135(9):2223-31. doi: 10.1002/ijc.28865. Epub 2014 Apr 5. PubMed PMID: 24668305.
10: Prebet T, Sun Z, Figueroa ME, Ketterling R, Melnick A, Greenberg PL, Herman J, Juckett M, Smith MR, Malick L, Paietta E, Czader M, Litzow M, Gabrilove J, Erba HP, Gore SD, Tallman MS. Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905. J Clin Oncol. 2014 Apr 20;32(12):1242-8. doi: 10.1200/JCO.2013.50.3102. Epub 2014 Mar 24. PubMed PMID: 24663049; PubMed Central PMCID: PMC3986386.