Target Validation Information
Target ID T89361
Target Name Cell division protein kinase 6
Target Type
Successful
Drug Potency against Target PD-332991 Drug Info Ki = 15 nM [552469]
Flavopiridol Drug Info IC50 = 60 nM [537564]
FISETIN Drug Info IC50 = 850 nM [527422]
CHRYSIN Drug Info IC50 = 6000 nM [527422]
APIGENIN Drug Info IC50 = 1700 nM [527422]
Action against Disease Model PD-332991 Inhibited cellular proliferation with IC50 = 40-400 nM in RB1-positive cell lines and IC50 > 3 mM in RB1-negative cell lines; induced G1 arrest in primary bone marrow myeloma cells and prevented t uMour growth in disseminated h uMan myeloma xenografts; promoted t uMour regression in mice with a h uMan colon carcinoma xenograft. [537564] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations In unstressed thymocytes, CDK6 kinase activity is lost in CDK6 KO animals; the thymic defects observed in the KO animals are the result of changes in CDK6 protein level resulting from the presence of the LSL cassette; CDK6 loss interferes with the proliferation and survival signals instigated by Notch signaling.Further,those thymocytes that survive CDK6 loss display defects in maturation consistent with a role for CDK6 in potentiating early stages and inhibiting late stages of Notch-regulated differentiation. [552469]
References
Ref 552469Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 527422J Med Chem. 2005 Feb 10;48(3):737-43.Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.
Ref 527422J Med Chem. 2005 Feb 10;48(3):737-43.Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.
Ref 527422J Med Chem. 2005 Feb 10;48(3):737-43.Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.

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