Uzansertib phosphate  (Synonyms: INCB053914 phosphate)

Uzansertib (INCB053914) phosphate is an orally active, ATP-competitive pan-PIM kinase inhibitor with IC₅₀s of 0.24 nM, 30 nM, 0.12 nM for PIM1, PIM2, PIM3, respectively. Uzansertib phosphate has broad anti-proliferative activity against a variety of hematologic tumor cell lines^[1].

Uzansertib phosphate inhibits proliferation in all multiple myeloma (MM) cell lines tested, with mean GI₅₀ values ranging from 13.2 nM to 230.0 nM in AML, MM, DLBCL, MCL, and T-ALL cell lines^[1].
Uzansertib phosphate (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 phosphate (mean IC₅₀, 4 nM and 27 nM, respectively)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Uzansertib phosphate (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 phosphate demonstrates a dose-dependent inhibition of BAD phosphorylation relative to vehicle at 4 hours post dose (MOLM-16 tumors, IC₅₀=70 nM; KMS-12-BM tumors, IC₅₀=145 nM) ^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

611.51

Solid

C₂₆H₂₉F₃N₅O₇P

2088852-47-3

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Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Koblish H, et al. Preclinical characterization of INCB053914, a novel pan-PIM kinase inhibitor, alone and in combination with anticancer agents, in models of hematologic malignancies. PLoS One. 2018 Jun 21;13(6):e0199108.  [Content Brief]