2CCT

HUMAN HSP90 WITH 5-(5-CHLORO-2,4-DIHYDROXY-PHENYL)-4-PIPERAZIN-1-YL- 2H-PYRAZOLE-3-CARBOXYLIC ACID ETHYLAMIDE

Summary for 2CCT

• Entry DOI: 10.2210/pdb2cct/pdb
• Related: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM 2BT0 2BYH 2BYI 2BZ5 2C2L 2CCS 2CCU
• Descriptor: HEAT SHOCK PROTEIN HSP-90 ALPHA, 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-PIPERAZIN-1-YL-1H-PYRAZOLE-3-CARBOXAMIDE (3 entities in total)
• Functional Keywords: heat-shock protein complex, hsp90, atpase, pyrazole, chaperone, atp-binding, heat shock, nucleotide-binding, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : P07900
• Total number of polymer chains: 1
• Total formula weight: 26981.62

Authors

Barril, X.,Beswick, M.C.,Collier, A.,Drysdale, M.J.,Dymock, B.W.,Fink, A.,Grant, K.,Howes, R.,Jordan, A.M.,Massey, A.,Surgenor, A.,Wayne, J.,Workman, P.,Wright, L. (deposition date: 2006-01-18, release date: 2006-02-22, Last modification date: 2024-05-08)

Primary citation

Barril, X.,Beswick, M.C.,Collier, A.,Drysdale, M.J.,Dymock, B.W.,Fink, A.,Grant, K.,Howes, R.,Jordan, A.M.,Massey, A.,Surgenor, A.,Wayne, J.,Workman, P.,Wright, L.
4-Amino derivatives of the Hsp90 inhibitor CCT018159.
Bioorg. Med. Chem. Lett., 16:2543-2548, 2006

PubMed Abstract: Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported potent analogue VER-49009. The most potent of the new compounds has a methylsulfonylbenzyl substituent appended to the piperazine nitrogen, possesses an IC50 of less than 600 nM binding against the enzyme and demonstrates low micromolar inhibition of tumour cell proliferation.

PubMed: 16480864
DOI: 10.1016/j.bmcl.2006.01.099

Experimental method

X-RAY DIFFRACTION (2.3 Å)