Information
LY2857785 is a type I reversible and competitive ATP kinase inhibitor againstCDK9(IC50=0.011 μM) and also inhibits other transcription kinasesCDK8(IC50=0.016 μM) andCDK7(IC50=0.246 μM).
Targets
CDK9 (Cell-free assay); CDK8 (Cell-free assay); CDK7 (Cell-free assay) 0.011 μM; 0.016 μM; 0.246 μM
In vitro
LY2857785 shows good selectivity against a panel of 114 protein kinases, with only 5 other protein kinases inhibited with potency (IC50) less than 0.1 μmol/L, and a total of 14 kinases less than 1 μmol/L. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC50s 0.089 and 0.042 μM. Although LY2857785 inhibits CDK4, CDK6, and CDK2 enzymatic activities, it does not induce G1-S cell-cycle arrest. It also has activity against CDK1 (Histone H1 P-T153 inhibition IC50 0.241 μmol/L). However LY2857785 only induces a moderate G2–M DNA content increase, from 35% to 55%, with EC50 0.135 μmol/L. LY2857785 inhibits hematologic and solid tumor cell proliferation and induces apoptosis in vitro.
In vivo
LY2857785 inhibits RNAP II CTD Ser2 phosphorylation in vivo. It demonstrates potent antitumor growth efficacy in preclinical tumor models and increases animal survival. No significant weight loss is observed in the nude mouse study while animal mortality is observed in these studies at LY2957785 high-dose groups.
Cell Research(from reference)
Cell lines：Solid tumor cells/hematologic cell lines; i.e. Human A549 (lung carcinoma), U2OS (osteosarcoma), HCT116 (colorectal carcinoma), U87MG (glioblastoma), A375 (malignant melanoma), MV-4-11 (biphenotypic B-myelomonocytic leukemia), RPMI 8226 (myelo
Concentrations：0, 0.1, 0.2, 0.4, 0.6, 0.8, 1 μM
Incubation Time：2-72 h
