INCB054329

Research use only, not for human use.

INCB054329 is a novel potent, orally bioactive BET inhibitor that inhibits binding of BRD2, BRD3 and BRD4 to an acetylated histone H4 peptide with low nanomolar potency.

INCB054329 is a novel potent, orally bioactive BET inhibitor that inhibits binding of BRD2, BRD3 and BRD4 to an acetylated histone H4 peptide with low nanomolar potency; inhibits expression of c-MYC and induced HEXIM1 in myeloma cell lines; inhibits growth of the majority of myeloma, AML, and lymphoma cell lines with IC50<100 nM; induces G1 arrest and cell apoptosis consistent with increased expression of pro-apoptotic regulators; inhibits tumor growth in vivo.

INCB054329 is a bromodomain and extra-terminal motif (BET) inhibitor. INCB054329 inhibits binding of BRD2, BRD3 and BRD4 to an acetylated histone H4 peptide with low nanomolar potency. In myeloma cell lines, treatment with INCB054329 inhibits expression of c-MYC and induced HEXIM1. The majority of myeloma, AML, and lymphoma cell lines tested are growth inhibited by INCB054329 with potencies less than 200 nM. Selectivity is seen when compared with nontransformed cells as the potency for growth inhibition of IL-2 stimulated T-cells from normal donors is greater than 1300 nM. Cell cycle analysis reveals treatment-induced G1 arrest. Furthermore in both AML and lymphoma cell lines, INCB054329 induces apoptosis consistent with increased expression of pro-apoptotic regulators.

Oral administration of INCB054329 inhibits tumor growth in several models of hematologic cancers. In the MM1.S multiple myeloma xenograft model, inhibition of tumor growth is correlated with reduction of c-MYC levels. PK-PD analysis shows c-MYC suppression is associated with an IC50 value of less than 100 nM in vivo.

INCB 054329

Chromatin/Epigenetic

Bromodomain

Bromodomain

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1628607-64-6

348.362

C19H16N4O3

>98% (HPLC)

DMSO : ≥ 100 mg/mL 287.06 mM

O=C1N2[C@H](COC3=C2C(N1)=CC=C3C4=C(ON=C4C)C)C5=CC=CC=N5

(S)-6-(3,5-dimethylisoxazol-4-yl)-3-(pyridin-2-yl)-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylen-2(1H)-one

(-20℃)

With Ice Pack

≥ 2 years