KIT mutants bind ripretinib

Stable Identifier
Reaction [binding]
Homo sapiens
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Ripretinib is a example of a switch pocket inhibitor, a new type of class II tyrosine kinase inhibitors that is being developed for use against activation and drug resistant mutations in PDGFR and KIT (reviewed in Martin-Broto and Moura, 2020). Switch pocket inhibitors are type II tyrosine kinase inhibitors that force the activation loop (AL) into an inactive conformation, and are therefore active against AL mutants of KIT that are otherwise only sensitive to type I TKIs. Ripretinib is active against mutations affecting extracellular, juxtamembrane, ATP-binding pocket and activation loop domains and is thus the first inhibitor with pan-KIT inhibitory activity. Ripretinib has been successfully studied in TKI-refractory GIST (Smith et al, 2019).
Literature References
PubMed ID Title Journal Year
32541319 New drugs in gastrointestinal stromal tumors

Martín-Broto, J, Moura, DS

Curr Opin Oncol 2020
31085175 Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants

Hood, MM, Gupta, A, Su, Y, Ensinger, CL, Caldwell, TM, Bulfer, SL, Heinrich, MC, Al-Ani, G, Ahn, YM, Patt, WC, Janku, F, Turner, BA, Ruiz-Soto, R, Leary, CB, Abdul Razak, AR, Yates, K, Town, A, Rosen, O, Wise, SC, Vogeti, L, Telikepalli, H, Rutkoski, TJ, Vogeti, S, Smith, BD, Flynn, DL, Chun, L, Lu, WP, Kaufman, MD, McKinley, A

Cancer Cell 2019
Normal reaction
Functional status

Gain of function of ripretinib-sensitive KIT mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
gastrointestinal stromal tumor DOID:9253 GANT, GIST, Stromal tumor of gastrointestinal tract
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