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INCB057643
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
INCB057643图片
CAS NO:1820889-23-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 415.46
Formula C20H21N3O5S
CAS No. 1820889-23-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>60 mg/mL
Water: N/A
Ethanol: N/A
Chemical Name 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
Synonyms INCB057643; INCB-057643; INCB 057643
实验参考方法
In Vitro

In vitro activity: INCB057643 is a novel, orally bioavailable BET inhibitor that has been tested in preclinical models of hematologic malignancies. INCB057643 inhibited binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nM range, and was selective against other bromodomain containing proteins. Production of several cytokines, including IL-6, IL-10 and MIP-1α, was repressed by INCB057643 in human and mouse whole blood stimulated ex vivo with LPS. Consistent with these effects, analyses of gene expression in cells treated with INCB057643 revealed that pathways involved in cell cycle progression, apoptosis, and IL-6 were among the most significantly altered in vitro. Oral administration of INCB057643 resulted in significant anti-tumor efficacy in xenograft models of AML, myeloma, and DLBCL. Additionally, combining INCB057643 with standard of care agents used for the treatment of DLBCL including rituximab and bendamustine resulted in enhanced anti-tumor efficacy relative to that achieved with single agent therapies at doses that were well tolerated. In addition, many B cell malignancies are reliant on the PI3Kδ pathway for proliferation and survival, suggesting that the combination of INCB057643 with the clinical stage PI3Kδ specific inhibitor INCB050465 may be a rational therapeutic strategy for DLBCL. Compared with single agent BETi or PI3Kδi therapy, the combination significantly potentiated tumor growth inhibition in DLBCL models representative of the ABC subtype (HBL-1), and the double hit GCB subtype (WILL2). These data suggest that clinical exploration of INCB057643 as a monotherapy or in combination in hematologic malignancies is warranted.


Kinase Assay: INCB057643 is a novel, orally bioavailable BET inhibitor that has been tested in preclinical models of hematologic malignancies. INCB057643 inhibited binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nM range, and was selective against other bromodomain containing proteins.


Cell Assay: In vitro analyses showed that INCB057643 inhibited proliferation of human AML, DLBCL, and multiple myeloma cell lines, with a corresponding decrease in MYC protein levels. Cell cycle analyses indicated that G1 arrest and a concentration-dependent increase in apoptosis were seen within 48 hours of treatment with INCB057643.

In VivoProduction 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
Animal modelMouse xenograft models of AML, myeloma, and DLBCL
Formulation & DosageOral
References AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5071.