INCB057643

Research use only, not for human use.

INCB057643 is a novel potent, selective, orally bioavailable BET inhibitor.

INCB057643 is a novel potent, selective, orally bioavailable BET inhibitor; shows more effectivity against androgen-dependent (VCaP and LNCaP) than androgen-independent (DU145 and PC3) cells with IC50 of <100 nM and >500 nM, respectively; significantly causes inhibition of tumor growth in mice bearing 22Rv1 tumor xenografts.Solid Tumors Phase 2 Clinical.

INCB-057643 is a novel, orally bioavailable BET inhibitor. INCB-057643 inhibits binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nM range, and is selective against other bromodomain containing proteins. In vitro analyses show that INCB-057643 inhibits proliferation of human AML, DLBCL, and multiple myeloma cell lines, with a corresponding decrease in MYC protein levels. Cell cycle analyses indicate that G1 arrest and a concentration-dependent increase in apoptosis are seen within 48 hours of treatment with INCB-057643.

Production of several cytokines, including IL-6, IL-10 and MIP-1α, is repressed by INCB-057643 in human and mouse whole blood stimulated ex vivo with LPS. Oral administration of INCB-057643 results in significant anti-tumor efficacy in xenograft models of AML, myeloma, and DLBCL. Additionally, combining INCB-057643 with standard of care agents used for the treatment of DLBCL including rituximab and bendamustine results in enhanced anti-tumor efficacy relative to that achieved with single agent therapies at doses that are well tolerated.

INCB 057643

Chromatin/Epigenetic

Bromodomain

BET

Cancer

Solid Tumors

1820889-23-3

415.464

C20H21N3O5S

>98% (HPLC)

DMSO : 62.5 mg/mL 150.44 mM

CN(C(C(C)(C)O1)=O)C2=C1C(C(C3=C4NC=C3)=CN(C)C4=O)=CC(S(C)(=O)=O)=C2

2,2,4-trimethyl-8-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-6-(methylsulfonyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(-20℃)

With Ice Pack

≥ 2 years