Structure-guided rescaffolding of selective antagonists of BCL-XL

Michael F T Koehler, Philippe Bergeron, Edna F Choo, Kevin Lau, Chudi O Ndubaku, Danette Andrea Dudley, Paul Gibbons, Brad Sleebs, Carl S Rye, George Nikolakopoulos, Chinh Thien Bui, Sanjitha Kulasegaram, Wilhelmus J A Kersten, Brian J Smith, Peter Edward Czabotar, Peter M Colman, David CS Huang, Jonathan Bayldon Baell, Keith Geoffrey Watson, Lisa Hasvold & 7 others Zhi-Fu Tao, Le Wang, Andrew J Souers, Steven W Elmore, John A Flygare, Wayne J Fairbrother, Guillaume Lessene

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin s lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.
Original languageEnglish
Pages (from-to)662 - 667
Number of pages6
JournalA C S Medicinal Chemistry Letters
Volume5
Issue number8
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Koehler, M. F. T., Bergeron, P., Choo, E. F., Lau, K., Ndubaku, C. O., Dudley, D. A., ... Lessene, G. (2014). Structure-guided rescaffolding of selective antagonists of BCL-XL. A C S Medicinal Chemistry Letters, 5(8), 662 - 667. https://doi.org/10.1021/ml500030p
Koehler, Michael F T ; Bergeron, Philippe ; Choo, Edna F ; Lau, Kevin ; Ndubaku, Chudi O ; Dudley, Danette Andrea ; Gibbons, Paul ; Sleebs, Brad ; Rye, Carl S ; Nikolakopoulos, George ; Bui, Chinh Thien ; Kulasegaram, Sanjitha ; Kersten, Wilhelmus J A ; Smith, Brian J ; Czabotar, Peter Edward ; Colman, Peter M ; Huang, David CS ; Baell, Jonathan Bayldon ; Watson, Keith Geoffrey ; Hasvold, Lisa ; Tao, Zhi-Fu ; Wang, Le ; Souers, Andrew J ; Elmore, Steven W ; Flygare, John A ; Fairbrother, Wayne J ; Lessene, Guillaume. / Structure-guided rescaffolding of selective antagonists of BCL-XL. In: A C S Medicinal Chemistry Letters. 2014 ; Vol. 5, No. 8. pp. 662 - 667.
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title = "Structure-guided rescaffolding of selective antagonists of BCL-XL",
abstract = "Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin s lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.",
author = "Koehler, {Michael F T} and Philippe Bergeron and Choo, {Edna F} and Kevin Lau and Ndubaku, {Chudi O} and Dudley, {Danette Andrea} and Paul Gibbons and Brad Sleebs and Rye, {Carl S} and George Nikolakopoulos and Bui, {Chinh Thien} and Sanjitha Kulasegaram and Kersten, {Wilhelmus J A} and Smith, {Brian J} and Czabotar, {Peter Edward} and Colman, {Peter M} and Huang, {David CS} and Baell, {Jonathan Bayldon} and Watson, {Keith Geoffrey} and Lisa Hasvold and Zhi-Fu Tao and Le Wang and Souers, {Andrew J} and Elmore, {Steven W} and Flygare, {John A} and Fairbrother, {Wayne J} and Guillaume Lessene",
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doi = "10.1021/ml500030p",
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journal = "A C S Medicinal Chemistry Letters",
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Koehler, MFT, Bergeron, P, Choo, EF, Lau, K, Ndubaku, CO, Dudley, DA, Gibbons, P, Sleebs, B, Rye, CS, Nikolakopoulos, G, Bui, CT, Kulasegaram, S, Kersten, WJA, Smith, BJ, Czabotar, PE, Colman, PM, Huang, DCS, Baell, JB, Watson, KG, Hasvold, L, Tao, Z-F, Wang, L, Souers, AJ, Elmore, SW, Flygare, JA, Fairbrother, WJ & Lessene, G 2014, 'Structure-guided rescaffolding of selective antagonists of BCL-XL' A C S Medicinal Chemistry Letters, vol. 5, no. 8, pp. 662 - 667. https://doi.org/10.1021/ml500030p

Structure-guided rescaffolding of selective antagonists of BCL-XL. / Koehler, Michael F T; Bergeron, Philippe; Choo, Edna F; Lau, Kevin; Ndubaku, Chudi O; Dudley, Danette Andrea; Gibbons, Paul; Sleebs, Brad; Rye, Carl S; Nikolakopoulos, George; Bui, Chinh Thien; Kulasegaram, Sanjitha; Kersten, Wilhelmus J A; Smith, Brian J; Czabotar, Peter Edward; Colman, Peter M; Huang, David CS; Baell, Jonathan Bayldon; Watson, Keith Geoffrey; Hasvold, Lisa; Tao, Zhi-Fu; Wang, Le; Souers, Andrew J; Elmore, Steven W; Flygare, John A; Fairbrother, Wayne J; Lessene, Guillaume.

In: A C S Medicinal Chemistry Letters, Vol. 5, No. 8, 2014, p. 662 - 667.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structure-guided rescaffolding of selective antagonists of BCL-XL

AU - Koehler, Michael F T

AU - Bergeron, Philippe

AU - Choo, Edna F

AU - Lau, Kevin

AU - Ndubaku, Chudi O

AU - Dudley, Danette Andrea

AU - Gibbons, Paul

AU - Sleebs, Brad

AU - Rye, Carl S

AU - Nikolakopoulos, George

AU - Bui, Chinh Thien

AU - Kulasegaram, Sanjitha

AU - Kersten, Wilhelmus J A

AU - Smith, Brian J

AU - Czabotar, Peter Edward

AU - Colman, Peter M

AU - Huang, David CS

AU - Baell, Jonathan Bayldon

AU - Watson, Keith Geoffrey

AU - Hasvold, Lisa

AU - Tao, Zhi-Fu

AU - Wang, Le

AU - Souers, Andrew J

AU - Elmore, Steven W

AU - Flygare, John A

AU - Fairbrother, Wayne J

AU - Lessene, Guillaume

PY - 2014

Y1 - 2014

N2 - Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin s lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

AB - Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin s lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

U2 - 10.1021/ml500030p

DO - 10.1021/ml500030p

M3 - Article

VL - 5

SP - 662

EP - 667

JO - A C S Medicinal Chemistry Letters

JF - A C S Medicinal Chemistry Letters

SN - 1948-5875

IS - 8

ER -

Koehler MFT, Bergeron P, Choo EF, Lau K, Ndubaku CO, Dudley DA et al. Structure-guided rescaffolding of selective antagonists of BCL-XL. A C S Medicinal Chemistry Letters. 2014;5(8):662 - 667. https://doi.org/10.1021/ml500030p