Milciclib is a potent inhibitor of cyclin-dependent kinases (IC50s: CDK1 = 398 nM, CDK2 = 45 nM, CDK4 = 160 nM, CDK5 = 265 nM, CDK7 = 150 nM).1 It is also a potent inhibitor of TRKA and C (IC50 = A, 53 nM, C, 134 nM). Milciclib displayed antitumor activity across multiple cancer cell lines including lymphoma, colon, kidney, ovarian, NSCLC, neuroblastoma, and osteosarcoma.2 It was also active in various human cancer xenograft and other models. It showed antitumor activity in malignant glioma cells and acted synergistically with temozolomide.3 Milciclib displayed efficacy in combination with gemcitabine in patients with refractory solid tumors.4 It blocked glucose consumption in H460 and H1975 cells by decreasing SLC2A1 mRNA and protein levels and inhibiting glucose transport via CDK7 inhibition.5
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