Structure-based drug design of a highly potent CDK1,2,4,6 inhibitor with novel macrocyclic quinoxalin-2-one structure

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 19, 2006, Pages 5122-5126

  Kawanishi, Nobuhiko ^a   Sugimoto, Tetsuya ^a   Shibata, Jun ^a   Nakamura, Kaori ^a   Masutani, Kouta ^a   Ikuta, Mari ^a   Hirai, Hiroshi ^a  

^a TAIHO PHARMACEUTICAL CO LTD   (Japan)

Author keywords

CDK inhibitor; CDK1; CDK2; CDK4; CDK4 mimic CDK4; CDK6; E2F; X ray

Indexed keywords

CYCLIN DEPENDENT KINASE 1,2,4,6 INHIBITOR; CYCLIN DEPENDENT KINASE INHIBITOR; MACROCYCLIC COMPOUND; QUINOXALINE DERIVATIVE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG DESIGN; DRUG INHIBITION; DRUG POTENCY; DRUG STRUCTURE; HYDROGEN BOND; IC 50; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; X RAY CRYSTALLOGRAPHY;

ANIMALS; BINDING SITES; CDC2 PROTEIN KINASE; CDC2-CDC28 KINASES; CRYSTALLOGRAPHY, X-RAY; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASE 4; CYCLIN-DEPENDENT KINASE 6; DRUG DESIGN; HUMANS; HYDROGEN BONDING; INHIBITORY CONCENTRATION 50; MACROCYCLIC COMPOUNDS; MOLECULAR STRUCTURE; QUINOXALINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33747336252     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.07.026     Document Type: Article

References (20)

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13. The X-ray coordinate has been deposited with the Protein Data Bank, as entry 1GII.
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19. +.
20. 50 > 1 μM against Abl, Arg, Aurora-A, Axl, Blk, Bmx, CaMKIV, Chk1, Chk2, c-RAF, CSK, ERK1, ERK2, KDR, Flt-1, FGFR1, FGFR2, FGFR3, IGF-1R, IKKα, IKKβ, JNK1α1, JNK2α2, JNK3, Lyn, MAPK1, MAPK2, MAPKAP-K2, MEK1, MKK4, MKK6, MKK7β, p70S6K, PAK2, PDGFRα, PDGFRβ, PDK1, PKA, PKBα, PKBβ, PKγ, PKCα, PKCβII, PKCγ, PKCδ, PKCε, PKCη, PKCι, PKCμ, PKD2, PRAK, PRK2, ROCK-II, Rsk2, SAPK2a, SAPK2b, SAPK3, SAPK4, SGK, Syk, Tie-2 and ZAP-70.