Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that participate in cell cycle regulation. The functionally distinct kinase complexes are formed by the combination of catalytic kinase subunits (such as CDK1, CDK2, CDK4, or CDK6) with regulatory cyclin subunits (such as cyclin A, B, D1, D2, D3, or E). Coordinated activation of these complexes at specific times drives cells through the cell cycle and ensures the fidelity of cell division.
The Aurora kinases also have a critical role in controlling chromosome movement and organization, thus regulating cell cycle. Aurora-A contributes to formation of the mitotic spindle apparatus that guarantees accurate segregation of chromosomes into daughter cells; Aurora-B is required for cytokinesis and proper chromosome architecture during mitosis.
JNJ-7706621 is a dual CDK and aurora inhibitor. Based on results from in vitro kinase assays utilizing human recombinant enzymes, JNJ-7706621 inhibited CDK1/Cyclin B, CDK2/Cyclin A, CDK2/Cyclin E, Aurora-A and Aurora-B with IC50s of 9 nM, 4 nM, 3 nM, 11 nM and 15 nM, respectively. JNJ-7706621 showed potent growth inhibition in vitro on human cancer cell lines of Hela, HCT-116, SKOV-3, PC3, A375, MDA-MB-231, DU145 with IC50 values ranging from 112 to 514 nM. Cell cycle analysis on Hela cells synchronized in G1 showed that cells treated with 3 μM JNJ-7706621 did not enter the S phase until 16 hours after G1 synchronization, indicating that JNJ-7706621 delayed exit from G1 and arrested cells in G2-M.
In a human tumor xenograft model established by implantation of A375 tumor fragments in female nu/nu mice, JNJ-7706621 given i.p. when the tumors reached approximately 62 to 126 mg at the dose of 125 mg/kg with the 7 on/7 off schedule or the 100 mg/kg daily schedule both produced identical tumor growth inhibition values of 93%[3].
JNJ-7706621 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
HCT116 cells
Function assay
In vitro inhibitory concentration against cell proliferation in human HCT116 (colon carcinoma) tumor cells, IC50=0.25 μM
15974571
human A375 cells
Proliferation assay
Antiproliferative activity against human A375 cells, IC50=0.447 μM
16682186
human HeLa cells
Function assay
In vitro inhibitory concentration against cell proliferation in human HeLa (cervical adenocarcinoma) tumor cells, IC50=0.28 μM
15974571
MDA-MB-231 cells
Function assay
In vitro inhibitory concentration against cell proliferation in various human MDA-MB-231 (breast carcinoma) tumor cells, IC50=0.59 μM
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