The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

Kwai-Ming J. Cheung; Thomas P. Matthews; Karen Ball; Martin Rowlands; Kathy Boxall; Swee Sharp; Alison Maloney; S. Mark Roe; Chrisostomos Prodromou; Laurence Pearl; Wynne Aherne; Edward MacDonald; Paul Workman

doi:10.1016/j.bmcl.2005.05.046

The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

Kwai-Ming J. Cheung, Thomas P. Matthews, Karen Ball, Martin Rowlands, Kathy Boxall, Swee Sharp, Alison Maloney, S. Mark Roe, Chrisostomos Prodromou, Laurence Pearl, Wynne Aherne, Edward MacDonald, Paul Workman

Institute of Life Sciences and Healthcare

Research output: Contribution to journal › Article › peer-review

Abstract

High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure–activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.

Original language	English
Pages (from-to)	3338-3343
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	15
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2005.05.046
Publication status	Published - 15 Jul 2005

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Cheung, K.-M. J., Matthews, T. P., Ball, K., Rowlands, M., Boxall, K., Sharp, S., Maloney, A., Roe, S. M., Prodromou, C., Pearl, L., Aherne, W., MacDonald, E., & Workman, P. (2005). The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors. Bioorganic & Medicinal Chemistry Letters, 15(14), 3338-3343. https://doi.org/10.1016/j.bmcl.2005.05.046

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title = "The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors",

abstract = "High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure–activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.",

author = "Cheung, {Kwai-Ming J.} and Matthews, {Thomas P.} and Karen Ball and Martin Rowlands and Kathy Boxall and Swee Sharp and Alison Maloney and Roe, {S. Mark} and Chrisostomos Prodromou and Laurence Pearl and Wynne Aherne and Edward MacDonald and Paul Workman",

year = "2005",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2005.05.046",

language = "English",

volume = "15",

pages = "3338--3343",

journal = "Bioorganic & Medicinal Chemistry Letters",

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Cheung, K-MJ, Matthews, TP, Ball, K, Rowlands, M, Boxall, K, Sharp, S, Maloney, A, Roe, SM, Prodromou, C, Pearl, L, Aherne, W, MacDonald, E & Workman, P 2005, 'The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors', Bioorganic & Medicinal Chemistry Letters, vol. 15, no. 14, pp. 3338-3343. https://doi.org/10.1016/j.bmcl.2005.05.046

TY - JOUR

T1 - The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

AU - Cheung, Kwai-Ming J.

AU - Matthews, Thomas P.

AU - Ball, Karen

AU - Rowlands, Martin

AU - Boxall, Kathy

AU - Sharp, Swee

AU - Maloney, Alison

AU - Roe, S. Mark

AU - Prodromou, Chrisostomos

AU - Pearl, Laurence

AU - Aherne, Wynne

AU - MacDonald, Edward

AU - Workman, Paul

PY - 2005/7/15

Y1 - 2005/7/15

N2 - High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure–activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.

AB - High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure–activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.

U2 - 10.1016/j.bmcl.2005.05.046

DO - 10.1016/j.bmcl.2005.05.046

M3 - Article

SN - 0960-894X

VL - 15

SP - 3338

EP - 3343

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 14

ER -

The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

Abstract

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