PDGFR mutants bind type I TKIs

Stable Identifier
Reaction [binding]
Homo sapiens
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Avipritinib, crenolanib, pazopanib and other type I tyrosine kinase inhibitors bind to the active form of the PDGF receptors and prevent their trans-autophosphorylation (reviewed in Roskoski, 2018; Klug et al, 2018; Papadopoulos and Lennartsson, 2016). PDGFRA receptors with mutations that strongly promote the active state, such as mutations in the kinase domain or the gatekeeper mutation T674I tend to be sensitive to type I TKIs. In contrast, the extracellular domain mutation Y288C is resistant to type I TKIs (Ip et al, 2018; reviewed in Roskoski, 2018; Klug et al, 2018).
Literature References
PubMed ID Title Journal Year
30389923 Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies

Vellano, CP, Scott, KL, Ju, Z, Jeong, KJ, Shao, SH, Leonard, PG, Woessner, R, Mills, GB, Sahni, N, Ip, CKM, Hua, X, Ng, PKS

Nat Commun 2018
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

Pharmacol. Ther. 2018
29137923 The PDGF/PDGFR pathway as a drug target

Lennartsson, J, Papadopoulos, N

Mol. Aspects Med. 2018
Normal reaction
Functional status

Gain of function of type I TKI sensitive PDGFR mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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