Molecular Formula | C19H16N4O3 |
Molar Mass | 348.36 |
Density | 1.46±0.1 g/cm3(Predicted) |
pKa | 12.48±0.40(Predicted) |
Storage Condition | 2-8℃ |
Use | INCB054329 is a potent BET inhibitor. |
In vitro study | INCB054329 at 3 μm had no significant inhibitory activity against the 16 non-BET bromine regions. The average GI50 for INCB054329 was 152 nM in 32 hematologic disease cancer cell lines containing cells isolated from acute myeloid leukemia, non-Hodgkin's lymphoma and multiple myeloma. In contrast, in T cells isolated from normal volunteers, stimulated with IL2 ex vivo, INCB054329 had a GI50 value of 2.435 μm. Its inhibitory effect on cell growth is related to the G1 phase arrest of cells. INCB054828 is also a selective inhibitor of FGFR1, 2, 3. In myeloma cell lines, treatment with INCB054329 inhibited expression by c-myc, inducing hexim1. In AML and lymphoma cell lines, INCB054329 induces apoptosis, with elevated expression of pro-apoptotic regulators. INCB054329 can reduce the expression of homologous recombination components, reduce cell growth, enhance PARPi and cisplatin-induced DNA damage and apoptosis. |
In vivo study | In mice, INCB054329 has high clearance and short half-life. INCB054329 was effective and well tolerated in the c-myc and mm1. s xenograft tumor models at exposure levels sufficient to effectively inhibit KMS-12-BM. In vivo, oral INCB054329 inhibits tumor growth in a variety of hematologic cancer models. |