Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants

被引：225

作者：

Smith, Bryan D. ^{[1
]}

Kaufman, Michael D. ^{[1
]}

Lu, Wei-Ping ^{[1
]}

Gupta, Anu ^{[1
]}

Leary, Cynthia B. ^{[1
]}

Wise, Scott C. ^{[1
,7
]}

Rutkoski, Thomas J. ^{[1
]}

Ahn, Yu Mi ^{[1
]}

Al-Ani, Gada ^{[1
]}

Bulfer, Stacie L. ^{[1
]}

Caldwell, Timothy M. ^{[1
]}

Chun, Lawrence ^{[2
]}

Ensinger, Carol L. ^{[1
]}

Hood, Molly M. ^{[1
]}

McKinley, Arin ^{[5
,6
]}

Patti, William C. ^{[1
]}

Ruiz-Soto, Rodrigo ^{[1
]}

Su, Ying ^{[1
]}

Telikepalli, Hanumaiah ^{[1
]}

Town, Ajia ^{[5
,6
]}

Turner, Benjamin A. ^{[1
]}

Vogeti, Lakshminarayana ^{[1
]}

Vogeti, Subha ^{[1
]}

Yates, Karen ^{[1
]}

Janku, Filip ^{[3
]}

Razak, Albiruni Ryan Abdul ^{[4
]}

Rosen, Oliver ^{[1
]}

Heinrich, Michael C. ^{[5
,6
]}

Flynn, Daniel L. ^{[1
]}

机构：

[1] Deciphera Pharmaceut Inc, Waltham, MA 02451 USA

[2] Emerald Biostruct, Bainbridge Isl, WA 98110 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA

[4] Princess Margaret Canc Ctr, Canc Clin Res Unit, Toronto, ON, Canada

[5] Portland VA Med Ctr, Portland, OR 97239 USA

[6] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[7] MI Biores, Ann Arbor, MI 48108 USA

来源：

CANCER CELL | 2019年 / 35卷 / 05期

关键词：

TYROSINE KINASE; C-KIT; MUTATIONS; ACTIVATION; IMATINIB; MASTOCYTOSIS; MECHANISMS; CELLS; AMPLIFICATION; MIDOSTAURIN;

D O I：

10.1016/j.ccell.2019.04.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Ripretinib is a "switch-control" kinase inhibitor that forces the activation loop (or activation "switch") into an inactive conformation. Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors. Ripretinib shows efficacy in preclinical cancer models, and preliminary clinical data provide proof-of-concept that ripretinib inhibits a wide range of KIT mutants in patients with drug-resistant GISTs.

引用

页码：738 / +

页数：23

共 61 条

[1] Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors that do not require binding into the canonical ATP hinge region [J].

Ahn, Yu Mi ;

Clare, Michael ;

Ensinger, Carol L. ;

Hood, Molly M. ;

Lord, John W. ;

Lu, Wei-Ping ;

Miller, David F. ;

Patt, William C. ;

Smith, Bryan D. ;

Vogeti, Lakshminarayana ;

Kaufman, Michael D. ;

Petillo, Peter A. ;

Wise, Scott C. ;

Abendroth, Jan ;

Chun, Lawrence ;

Clark, Robin ;

Feese, Michael ;

Kim, Hidong ;

Stewart, Lance ;

Flynn, Daniel L. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (19) :5793-5798

[2] Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity [J].

Anastassiadis, Theonie ;

Deacon, Sean W. ;

Devarajan, Karthik ;

Ma, Haiching ;

Peterson, Jeffrey R. .

NATURE BIOTECHNOLOGY, 2011, 29 (11) :1039-U117

[3] KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis [J].

Arock, M. ;

Sotlar, K. ;

Akin, C. ;

Broesby-Olsen, S. ;

Hoermann, G. ;

Escribano, L. ;

Kristensen, T. K. ;

Kluin-Nelemans, H. C. ;

Hermine, O. ;

Dubreuil, P. ;

Sperr, W. R. ;

Hartmann, K. ;

Gotlib, J. ;

Cross, N. C. P. ;

Haferlach, T. ;

Garcia-Montero, A. ;

Orfao, A. ;

Schwaab, J. ;

Triggiani, M. ;

Horny, H-P ;

Metcalfe, D. D. ;

Reiter, A. ;

Valent, P. .

LEUKEMIA, 2015, 29 (06) :1223-1232

[4] KIT Gene Mutations and Copy Number in Melanoma Subtypes [J].

Beadling, Carol ;

Jacobson-Dunlop, Erick ;

Hodi, F. Stephen ;

Le, Claudia ;

Warrick, Andrea ;

Patterson, Janice ;

Town, Ajia ;

Harlow, Amy ;

Cruz, Frank, III ;

Azar, Sharl ;

Rubin, Brian P. ;

Muller, Susan ;

West, Rob ;

Heinrich, Michael C. ;

Corless, Christopher L. .

CLINICAL CANCER RESEARCH, 2008, 14 (21) :6821-6828

[5] Molecular Defects in Mastocytosis KIT and Beyond KIT [J].

Bibi, Siham ;

Langenfeld, Florent ;

Jeanningros, Sylvie ;

Brenet, Fabienne ;

Soucie, Erinn ;

Hermine, Olivier ;

Damaj, Gandhi ;

Dubreuil, Patrice ;

Arock, Michel .

IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA, 2014, 34 (02) :239-+

[6] A decade of tyrosine kinase inhibitor therapy: Historical and current perspectives on targeted therapy for GIST [J].

Blay, Jean-Yves .

CANCER TREATMENT REVIEWS, 2011, 37 (05) :373-384

[7] Oncogenic kinase signalling [J].

Blume-Jensen, P ;

Hunter, T .

NATURE, 2001, 411 (6835) :355-365

[8] The Somatic Genomic Landscape of Glioblastoma [J].

Brennan, Cameron W. ;

Verhaak, Roel G. W. ;

McKenna, Aaron ;

Campos, Benito ;

Noushmehr, Houtan ;

Salama, Sofie R. ;

Zheng, Siyuan ;

Chakravarty, Debyani ;

Sanborn, J. Zachary ;

Berman, Samuel H. ;

Beroukhim, Rameen ;

Bernard, Brady ;

Wu, Chang-Jiun ;

Genovese, Giannicola ;

Shmulevich, Ilya ;

Barnholtz-Sloan, Jill ;

Zou, Lihua ;

Vegesna, Rahulsimham ;

Shukla, Sachet A. ;

Ciriello, Giovanni ;

Yung, W. K. ;

Zhang, Wei ;

Sougnez, Carrie ;

Mikkelsen, Tom ;

Aldape, Kenneth ;

Bigner, Darell D. ;

Van Meir, Erwin G. ;

Prados, Michael ;

Sloan, Andrew ;

Black, Keith L. ;

Eschbacher, Jennifer ;

Finocchiaro, Gaetano ;

Friedman, William ;

Andrews, David W. ;

Guha, Abhijit ;

Iacocca, Mary ;

O'Neill, Brian P. ;

Foltz, Greg ;

Myers, Jerome ;

Weisenberger, Daniel J. ;

Penny, Robert ;

Kucherlapati, Raju ;

Perou, Charles M. ;

Hayes, D. Neil ;

Gibbs, Richard ;

Marra, Marco ;

Mills, Gordon B. ;

Lander, Eric ;

Spellman, Paul ;

Wilson, Richard .

CELL, 2013, 155 (02) :462-477

[9] Conformational Control Inhibition of the BCR-ABL1 Tyrosine Kinase, Including the Gatekeeper T315I Mutant, by the Switch-Control Inhibitor DCC-2036 [J].

Chan, Wayne W. ;

Wise, Scott C. ;

Kaufman, Michael D. ;

Ahn, Yu Mi ;

Ensinger, Carol L. ;

Haack, Torsten ;

Hood, Molly M. ;

Jones, Jennifer ;

Lord, John W. ;

Lu, Wei Ping ;

Miller, David ;

Patt, William C. ;

Smith, Bryan D. ;

Petillo, Peter A. ;

Rutkoski, Thomas J. ;

Telikepalli, Hanumaiah ;

Vogeti, Lakshminarayana ;

Yao, Tony ;

Chun, Lawrence ;

Clark, Robin ;

Evangelista, Peter ;

Gavrilescu, L. Cristina ;

Lazarides, Katherine ;

Zaleskas, Virginia M. ;

Stewart, Lance J. ;

Van Etten, Richard A. ;

Flynn, Daniel L. .

CANCER CELL, 2011, 19 (04) :556-568

[10] A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome [J].

Cools, J ;

DeAngelo, DJ ;

Gotlib, J ;

Stover, EH ;

Legare, RD ;

Cortes, J ;

Kutok, J ;

Clark, J ;

Galinsky, I ;

Griffin, JD ;

Cross, NCP ;

Tefferi, A ;

Malone, J ;

Alam, R ;

Schrier, SL ;

Schmid, J ;

Rose, M ;

Vandenberghe, P ;

Verhoef, G ;

Boogaerts, M ;

Wlodarska, I ;

Kantarjian, H ;

Marynen, P ;

Coutre, SE ;

Stone, R ;

Gilliland, DG .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (13) :1201-1214

← 1 2 3 4 5 6 7 →