Danusertib

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

一种有效的 ATP 竞争性 Aurora 激酶抑制剂，Aurora A、B 和 C 的 IC50 分别为 13,79 和 61 nM；还抑制 Abl、RET 和 FGFR1（IC50=25,31 和 47 nM）。

A potent, ATP-competitive Aurora kinase inhibitor with IC50 of 13,79 and 61 nM for Aurora A, B and C, respectively; Also inhibits Abl, RET, and FGFR1 (IC50=25,31, and 47 nM), efficiently inhibits imatinib-resistant Abl mutant T315I (IC50=5 nM); inhibits phosphorylation of histone H3 in Ser10, and has significant antitumor activity in different xenografts and spontaneous and transgenic animal tumor models.Blood Cancer Phase 2 Clinical(In Vitro):Danusertib (0.01 to 50 μM) significantly decreases viability of C13 and A2780cp cells. The IC50s are 10.40 and 1.83 μM for C13 cells, and 19.89 and 3.88 μM for A2780cp cells after 24- and 48-h treatment. Danusertib induces cell cycle arrest in G2/M phase in C13 and A2780cp cells. Danusertib treatment results in a marked increase in the percentage of cells arrested in G2/M phase and an accumulation of polyploidy in C13 and A2780cp cells. Danusertib demotes the expression of CDK1/CDC2 and cyclin B1 but promotes the expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induces autophagy in C13 and A2780cp cells with the involvement of PI3K/Akt/mTOR signaling pathway. PHA-739358 strongly inhibits proliferation of all leukemic cell lines tested, with IC50 values ranging from 0.05 μM to 3.06 μM. PHA-739358 induces antiproliferative effects in BaF3-p210 cells, including IM-resistant M351T, E255K, and T315I mutants. PHA-739358 (5 μM) reduces phosphorylation of CrkL in BaF3-p210 wt cells and IM-resistant mutants. Danusertibsertib leads to cell-cycle arrest and completely inhibits cell proliferation of the GEP-NET cells in vitro. (In Vivo):PHA-739358 (15 mg/kg twice a day, i.p.) and IM are well tolerated, and significantly inhibit proliferation of K562 cells andvirtually suppressed tumor growth during the 10-day treatment period. In a subcutaneous murine xenograft model, danusertibsertib (2×15 mg/kg/d, i.p.) significantly reduces tumor growth in vivo compared with controls or mice treated with streptozotocine/5-fluorouracil.

Danusertib (0.01 to 50 μM) significantly decreases viability of C13 and A2780cp cells. The IC50s are 10.40 and 1.83 μM for C13 cells, and 19.89 and 3.88 μM for A2780cp cells after 24- and 48-h treatment. Danusertib induces cell cycle arrest in G2/M phase in C13 and A2780cp cells. Danusertib treatment results in a marked increase in the percentage of cells arrested in G2/M phase and an accumulation of polyploidy in C13 and A2780cp cells. Danusertib demotes the expression of CDK1/CDC2 and cyclin B1 but promotes the expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induces autophagy in C13 and A2780cp cells with the involvement of PI3K/Akt/mTOR signaling pathway. PHA-739358 strongly inhibits proliferation of all leukemic cell lines tested, with IC50 values ranging from 0.05 μM to 3.06 μM. PHA-739358 induces antiproliferative effects in BaF3-p210 cells, including IM-resistant M351T, E255K, and T315I mutants. PHA-739358 (5 μM) reduces phosphorylation of CrkL in BaF3-p210 wt cells and IM-resistant mutants. Danusertibsertib leads to cell-cycle arrest and completely inhibits cell proliferation of the GEP-NET cells in vitro.

PHA-739358 (15 mg/kg twice a day, i.p.) and IM are well tolerated, and significantly inhibit proliferation of K562 cells andvirtually suppressed tumor growth during the 10-day treatment period. In a subcutaneous murine xenograft model, danusertibsertib (2×15 mg/kg/d, i.p.) significantly reduces tumor growth in vivo compared with controls or mice treated with streptozotocine/5-fluorouracil.

PHA-739358 | PHA739358 | PHA 739358

Cell Cycle/DNA Damage

Aurora Kinase

Abl|AuroraA|AuroraB|AuroraC|FGFR1|RET|TrkA

Cancer

Blood cancer

827318-97-8

474.5548

C26H30N6O3

>98% (HPLC)

DMSO: 7.5 mg/mL

O=C(NC1=NNC2=C1CN(C([C@H](OC)C3=CC=CC=C3)=O)C2)C4=CC=C(N5CCN(C)CC5)C=C4

Benzamide, 4-(4-methyl-1-piperazinyl)-N-[1,4,5,6-tetrahydro-5-[(2R)-2-methoxy-2-phenylacetyl]pyrrolo[3,4-c]pyrazol-3-yl]-

(-20℃)

With Ice Pack

≥ 2 years