INCB054329

INCB054329 shows no significant inhibitory activity against 16 non-BET bromodomains at 3 μM. In a panel of 32 hematologic cancer cell lines derived from acute myeloid leukemia, non-Hodgkin lymphoma, and multiple myeloma, the median 50% growth inhibition (GI50) value of INCB054329 is 152 nM (range, 26-5000 nM). In contrast to tumor cell lines, the GI50 value against T cells isolated from non-diseased donors stimulated ex vivo with IL-2 is 2.435 μM. Growth inhibition correlates with a concentration-dependent accumulation of cells in the G1 phase of the cell cycle. INCB054828 is also a selective kinase inhibitor of the FGFR 1, 2, and 3^[1]. In myeloma cell lines, treatment with INCB054329 inhibits expression of c-MYC and induced HEXIM1. In both AML and lymphoma cell lines, INCB054329 induces apoptosis consistent with increased expression of pro-apoptotic regulators^[2]. INCB054329 reduces expression of Homologous recombination (HR) components and co-operatively reduces cell growth and increases DNA damage and apoptosis induced by PARPi and cisplatin^[3].

INCB054329 exhibits high clearance in mice resulting in a short half-life. At exposures that effectively suppressed c-MYC, INCB054329 is found to be efficacious and well tolerated in both the KMS-12-BM and MM1.S xenograft models^[1]. In vivo, oral administration of INCB054329 inhibits tumor growth in several models of hematologic cancers^[2].

• Cell lines

  Myeloma, AML, DLBCL cells

• Concentrations

  --

• Incubation Time

  72 h

• Method

  Cell viability assay

• Animal Models

  KMS-12-BM tumors established in female Nu/Nu mice

• Dosages

  3, 10, 30, or 100 mg/kg

• Administration

  oral