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The target profiles of many drugs are established early in their development and are not systematically revisited at the time of FDA approval. Thus, it is often unclear whether therapeutics with the same nominal targets but different chemical structures are functionally equivalent. In this paper we use five different phenotypic and biochemical assays to compare approved inhibitors of cyclin-dependent kinases 4/6-collectively regarded as breakthroughs in the treatment of hormone receptor-positive breast cancer. We find that transcriptional, proteomic, and phenotypic changes induced by palbociclib, ribociclib, and abemaciclib differ significantly; abemaciclib in particular has advantageous activities partially overlapping those of alvocidib, an older polyselective CDK inhibitor. In cells and mice, abemaciclib inhibits kinases other than CDK4/6 including CDK2/cyclin A/E-implicated in resistance to CDK4/6 inhibition-and CDK1/cyclin B. The multifaceted experimental and computational approaches described here therefore uncover underappreciated differences in CDK4/6 inhibitor activities with potential importance in treating human patients.
Pubmed ID: 31178407 RIS Download
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This monoclonal targets Human E-Cadherin
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View all literature mentionsThis monoclonal targets Cyclin E1
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View all literature mentionsThis monoclonal targets Rb (4H1) Mouse mAb
View all literature mentionsMus musculus with name Crl:NU-Foxn1nu from IMSR.
View all literature mentionsCell line SUM149PT is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-BR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUM1315MO2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-453 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUM159PT is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-10A is a Spontaneously immortalized cell line with a species of origin Homo sapiens
View all literature mentionsCell line MDA-MB-157 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line hTERT-HME1 is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-361 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1500 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1419 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC38 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CAL-120 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CAL-85-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1143 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC70 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1954 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1806 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1428 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1395 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CAMA-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CAL-51 is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Human E-Cadherin
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