JNJ-7706621

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JNJ-7706621

CAS No. : 443797-96-4

MCE 国际站：JNJ-7706621

产品活性：JNJ-7706621 是一种有效的 aurora kinase 抑制剂，同时能有效抑制 CDK1 和 CDK2，对 CDK1，CDK2，aurora-A 和 aurora-B 的 IC₅₀ 值分别为 9 nM，3 nM，11 nM 和 15 nM。

研究领域：Cell Cycle/DNA Damage  |  Epigenetics  |  Apoptosis

作用靶点：Aurora Kinase  |  CDK  |  Apoptosis

In Vitro: JNJ-7706621 shows antiproliferative activity against various human tumor cells with IC₅₀s of 284, 254, and 447 nM for HeLa, HCT116, and A375, respectively. JNJ-7706621 inhibits other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase, but does not prevent localization of Aurora A to the spindle poles. Treatment of nocodazole-synchronized cells with JNJ-7706621 can override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. JNJ-7706621 shows inhibition of Aurora-A and Aurora-B but has no activity at the highest concentration tested on the Plk1 or Wee1 serine/threonine kinases. JNJ-7706621 also shows potent growth inhibition in vitro on all human cancer cell types with IC₅₀ values ranging from 112 to 514 nM. JNJ-7706621 suspensions inhibits cell viability of HeLa cells with IC₅₀s of 2.1 and 0.9 μg/mL at 24 and 48 h. The IC₅₀ of the JNJ-7706621-loaded nanoparticles are 35 and 2.7 μg/mL and the IC₅₀ of the JNJ-7706621-loaded micelles are 6.3 and 1.6 μg/mL.

In Vivo: JNJ-7706621 (100 and 125 mg/kg) is efficacious in a human tumor xenograft model under intermittent dosing regimens. JNJ-7706621 (100 mg/kg, i.p.) exhibits 95% tumor growth inhibition in A375 (human melanoma) tumor xenograft model. JNJ-7706621-loaded micelles inhibit tumor growth, and delay the tumor growth more efficiently than the control JNJ-7706621 suspension.

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