Uzansertib (INCB053914) is an orally active, ATP-competitive pan- PIM kinase inhibitor with IC 50 s of 0.24 nM, 30 nM, 0.12 nM for PIM1, PIM2, PIM3, respectively. Uzansertib has broad anti-proliferative activity against a variety of hematologic tumor cell lines.

Uzansertib inhibits proliferation in all multiple myeloma (MM) cell lines tested, with mean GI 50 values ranging from 13.2 nM to 230.0 nM in AML, MM, DLBCL, MCL, and T-ALL cell lines[1]. Uzansertib (0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM) inhibits the phosphorylation of downstream PIM kinase substrates (p70S6K/S6 and 4E-BP1) in a dose-dependent manner in MOLM-16 (AML), Pfeiffer (DLBCL), and KMS-12-PE/BM (MM) cell lines[1]. PIM kinase-mediated phosphorylation of BAD in MOLM-16 and KMS-12-BM cells is particularly sensitive to inhibition by Uzansertib (mean IC 50 , 4 nM and 27 nM, respectively)[1].

Uzansertib (25-100 mg/kg; PO; twice a day; for 15 days) inhibits tumor growth in a dose-dependent manner in mice bearing MOLM-16 (AML) or KMS-12-BM (MM)[1]. Uzansertib demonstrates a dose-dependent inhibition of BAD phosphorylation relative to vehicle at 4 hours post dose (MOLM-16 tumors, IC 50 =70 nM; KMS-12-BM tumors, IC 50 =145 nM)[1]. Animal Model: Female immune compromised (severe combined immunodeficiency [SCID]) mice (5-9 weeks of age) bearing MOLM-16 (AML) or KMS-12-BM (MM)[1]Dosage: 25, 50, 75, 100 mg/kg Administration: PO; twice a day; for 15 days Result: Inhibited tumor growth in a dose-dependent manner in mice.

1620012-39-6

C26H26F3N5O3

513.521

INCB053914;Uzansertib

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years