PDGFR mutants bind type I TKIs

Stable Identifier
R-HSA-9674427
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
30389923 Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies

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

Nat Commun 2018
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Klug, LR, Kent, JD, Heinrich, MC

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

Papadopoulos, N, Lennartsson, J

Mol. Aspects Med. 2018
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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