Biological Activity
INCB054329 (INCB-054329, INCB-54329) is a BET inhibitor with IC50 for BRD2-BD1, BRD2-BD2, BRD3-BD1, BRD3-BD2, BRD4-BD1, BRD4-BD2, BRDT-BD1 and BRDT-BD2, respectively Available in 44 nM, 5 nM, 9 nM, 1 nM, 28 nM, 3 nM, 119 nM and 63 nM.
in vitro
3 μM of INCB054329 had no significant inhibitory activity against 16 non-BET bromodomains. It had a mean GI50 of 152 nM in a group of 32 hematologic cancer cell lines isolated from acute myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma. In T cells isolated from normal volunteers, stimulated with IL2 in vitro, the GI50 value of it was 2.435 μM. Its growth inhibitory effect on cells is related to the arrest of cells in G1 phase. INCB054828 is also a selective inhibitor of FGFR1,2,3. In myeloma cell lines, treatment with it inhibited c-myc expression and induced HEXIM1. In AML and lymphoma cell lines, INCB054329 induced apoptosis and increased expression of pro-apoptotic regulators. It reduces the expression of homologous recombination components, reduces cell growth, and enhances PARPi and cisplatin-induced DNA damage and apoptosis.
in vivo
In mice, INCB-54329 has high clearance and short half-life. At exposures sufficient to effectively inhibit c-myc, it was effective and well tolerated in KMS-12-BM and MM1.S xenograft models. In vivo, oral administration of it inhibited tumor growth in multiple hematological cancer models.
target
| Target | Value |
BRD3-BD2
() | 1 nM |
BRD4 -BD2
() | 3 nM |
BRD2-BD2
() | 5 nM |
BRD3-BD1
() | 9 nM |
BRD4-BD1
() | 28 nM |
