title: Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles.
abstract: The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, 46285, Indianapolis, IN, USA. engler_thomas@lilly.com
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Engler
authors.forename: Kelly
authors.initials: K
authors.lastname: Furness
authors.forename: Sushant
authors.initials: S
authors.lastname: Malhotra
authors.forename: Concha
authors.initials: C
authors.lastname: Sanchez-Martinez
authors.forename: Chuan
authors.initials: C
authors.lastname: Shih
authors.forename: Walter
authors.initials: W
authors.lastname: Xie
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhu
authors.forename: Xun
authors.initials: X
authors.lastname: Zhou
authors.forename: Scott
authors.initials: S
authors.lastname: Conner
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Faul
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Kolis
authors.forename: Harold B
authors.initials: HB
authors.lastname: Brooks
authors.forename: Bharvin
authors.initials: B
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: Kashif
authors.initials: K
authors.lastname: Kirmani
authors.forename: Charles D
authors.initials: CD
authors.lastname: Spencer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Watkins
authors.forename: Eileen L
authors.initials: EL
authors.lastname: Considine
authors.forename: Jack A
authors.initials: JA
authors.lastname: Dempsey
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Ogg
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Stamm
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Anderson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Campbell
authors.forename: Vasu
authors.initials: V
authors.lastname: Vasudevan
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Lytle
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D012413:Rubidium / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D012413:Rubidium