title: Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides.
abstract: A series of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1-CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3-a]pyrrolo[3,4-c]carbazoles are consistently more active (8-42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.
authors.affiliation: DCR&T, Lilly Spain S.A., Avda de la Industria 30, 28108 Alcobendas, Madrid, Spain. sanchez-martinez_concepcion@lilly.com
authors.forename: Concha
authors.initials: C
authors.lastname: Sanchez-Martinez
authors.forename: Chuan
authors.initials: C
authors.lastname: Shih
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhu
authors.forename: Tiechao
authors.initials: T
authors.lastname: Li
authors.forename: Harold B
authors.initials: HB
authors.lastname: Brooks
authors.forename: Bharvin K R
authors.initials: BK
authors.lastname: Patel
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.forename: Tammy B
authors.initials: TB
authors.lastname: DeHahn
authors.forename: Charles D
authors.initials: CD
authors.lastname: Spencer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Watkins
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Ogg
authors.forename: Eileen
authors.initials: E
authors.lastname: Considine
authors.forename: Jack A
authors.initials: JA
authors.lastname: Dempsey
authors.forename: Faming
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D011758:Pyrroles; D018844:Cyclin-Dependent Kinases