PF-06873600 is an inhibitor of cyclin-dependent kinase 2 (Cdk2), Cdk4, and Cdk6 (Kis = 0.13, 1.25, and 0.11 nM, respectively).1 It is selective for these CDKs over Cdk1 and Cdk9 (Kis = 4.5 and 19.6 nM, respectively). PF-06873600 inhibits the phosphorylation of RB transcriptional corepressor 1 (RB1) in, and the proliferation of, OVCAR-3 ovarian cancer cells (EC50s = 19 and 45 nM, respectively). In vivo, PF-06873600 (30 mg/kg) reduces tumor volume in CTG-0464 and CTG-01912 non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) mouse models.
1.Freeman-Cook, K.D., Hoffman, R.L., Behenna, D.C., et al.Discovery of PF-06873600, a CDK2/4/6 inhibitor for the treatment of cancerJ. Med. Chem.64(13)9056-9077(2021)