Birabresib (OTX015)

Cas No.:	202590-98-5
Chemical Name:	OTX 015; OTX015,MK-8628; MK 8628; MK8628,OTX-015
Synonyms:	OTX 015; OTX015,MK-8628; MK 8628; MK8628,OTX-015
SMILES:	CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)O)C5=CC=C(C=C5)Cl)C
Formula:	C25H22ClN5O2S
M.Wt:	491.99
Purity:	98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Birabresib (OTX-015) is a potent bromodomain (BRD2/3/4) inhibitor with IC50s ranging from 92 to 112 nM.
In Vivo:	In MDA-MB-231 murine xenografts, tumor mass is significantly (p < 0.05) reduced by Birabresib (OTX-015) (50 mg/kg) with respect to vehicle-treated animals. Birabresib (OTX-015) in combination with 2 mg/kg everolimus shows more effective activity than Birabresib alone[4].
In Vitro:	Birabresib (OTX-015) (500 nM) exposure induces a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression is unchanged. c-MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels do correlate however with viability following exposure to Birabresib (OTX-015). Sequential combinations of Birabresib (OTX-015) with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line[2]. Birabresib (OTX-015) (0.1, 1, 5 μM) treatment induces HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal toxicity and effects on T cell activation. Birabresib-mediated activation of HIV-1 involves an increase in CDK9 occupancy and RNAP II C-terminal domain (CTD) phosphorylation[3].