Reactome | PDGFRs bind type I TKI

PDGFRs bind type I TKI

Stable Identifier

R-HSA-9674093

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Wild-type PDGFRA and PDGFRB can be bound and inhibited by class I tyrosine kinase inhibitors including pazopanib, avapritinib, and crenolanib (Gril et al, 2013; Wang et al, 2014; Mathias et al, 2015; Meliau et al, 2017; reviewed in Klug et al, 2018). Type I inhibitors bind in the ATP binding site of the active conformation and prevent full activation of the kinase (reviewed in Roskoski, 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
23583652	Pazopanib inhibits the activation of PDGFRβ-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells Gril, B, Palmieri, D, Qian, Y, Anwar, T, Liewehr, DJ, Steinberg, SM, Andreu, Z, Masana, D, Fernández, P, Steeg, PS, Vidal-Vanaclocha, F	Am. J. Pathol.	2013
25597754	The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations Mathias, TJ, Natarajan, K, Shukla, S, Doshi, KA, Singh, ZN, Ambudkar, SV, Baer, MR	Invest New Drugs	2015
29964125	Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases Klug, LR, Kent, JD, Heinrich, MC	Pharmacol. Ther.	2018
29093181	A precision therapy against cancers driven by KIT/PDGFRA mutations Evans, EK, Gardino, AK, Kim, JL, Hodous, BL, Shutes, A, Davis, A, Zhu, XJ, Schmidt-Kittler, O, Wilson, D, Wilson, K, DiPietro, L, Zhang, Y, Brooijmans, N, LaBranche, TP, Wozniak, A, Gebreyohannes, YK, Schöffski, P, Heinrich, MC, Deangelo, DJ, Miller, S, Wolf, B, Kohl, N, Guzi, T, Lydon, N, Boral, A, Lengauer, C	Sci Transl Med	2017
25328409	Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo Wang, P, Song, L, Ge, H, Jin, P, Jiang, Y, Hu, W, Geng, N	Onco Targets Ther	2014
28435517	Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines Melaiu, O, Catalano, C, De Santi, C, Cipollini, M, Figlioli, G, Pellè, L, Barone, E, Evangelista, M, Guazzelli, A, Boldrini, L, Sensi, E, Bonotti, A, Foddis, R, Cristaudo, A, Mutti, L, Fontanini, G, Gemignani, F, Landi, S	Genes Cancer	2017