INCB053914

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

INCB053914 (INCB-053914) 是一种新型有效、选择性 ATP 竞争性泛 PIM 激酶抑制剂，对 PIM1/2/3 的 IC50 分别为 0.24/30.0/0.12 nM。

INCB053914 (INCB-053914) is a novel potent, and selective ATP-competitive, pan-PIM kinase inhibitor with IC50 of 0.24/30.0/0.12 nM for PIM1/2/3, respectively; INCB053914 is highly selective against a panel of more than 50 kinases (>475-fold selectivity) with exception of RSK2 (IC50=7.1 uM); inhibits cellular proliferation in a panel of cell lines derived from hematologic malignancies including AML, MM, DLBCL, MCL, and T-ALL with GI50 of <100 nM, inhibits proliferation in all MM cell lines with GI5050 of 13.2-230.0 nM; inhibits PIM kinase-mediated phosphorylation of BAD in MOLM-16 and KMS-12-BM cells with IC50 of 4 and 27 nM, also increases PIM2 expression in KG-1a (AML), Pfeiffer, and KMS12-PE cells; in vivo, INCB053914 inhibited Bcl-2-associated death promoter protein phosphorylation and dose-dependently inhibited tumor growth in acute myeloid leukemia and multiple myeloma xenografts.Solid Tumors Phase 2 Clinical.

Uzansertib 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. 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. 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).

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) . 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) . Animal Model:Female immune compromised (severe combined immunodeficiency [SCID]) mice (5-9 weeks of age) bearing MOLM-16 (AML) or KMS-12-BM (MM)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.

INCB-053914

JAK/STAT Signaling

Pim

Pim

Cancer

Solid Tumors

1620012-39-6

513.521

C26H26F3N5O3

>98% (HPLC)

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O=C(NC1=CN=C2C(CC[C@H]2O)=C1N3C[C@@H](N)[C@H](O)[C@@H](C)C3)C4=NC(C5=C(F)C=CC=C5F)=C(F)C=C4

N-((R)-4-((3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

(-20℃)

With Ice Pack

≥ 2 years