Uzansertib (INCB053914) 是一种具有口服活性的，ATP 竞争性泛-PIM激酶抑制剂，对于 PIM1，PIM2 和 PIM3 的IC50分别为 0.24 nM，30 nM 和 0.12 nM。Uzansertib 对多种血液肿瘤细胞系具有广泛的抗增殖活性。
| 生物活性 | Uzansertib (INCB053914) is an orally active, ATP-competitive pan-PIMkinaseinhibitor withIC50s of 0.24 nM, 30 nM, 0.12 nM forPIM1,PIM2,PIM3, respectively. Uzansertib has broad anti-proliferative activity against a variety of hematologic tumor cell lines[1]. |
| IC50& Target[1] | PIM1 0.24 nM (IC50) | PIM2 30 nM (IC50) | PIM3 0.12 nM (IC50) |
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体外研究
(In Vitro) | Uzansertib inhibits proliferation in all multiple myeloma (MM) cell lines tested, with mean GI50values 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 IC50, 4 nM and 27 nM, respectively)[1].
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体内研究
(In Vivo) | 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, IC50=70 nM; KMS-12-BM tumors, IC50=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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
