PD-161570

PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM. PD-161570 also inhibits the PDGFR, EGFR and c-Src tyrosine kinases with IC50 values of 310 nM, 240 nM, and 44 nM, respectively. PD-161570 inhibits PDGF-stimulated autophosphorylation and FGF-1 receptor phosphorylation with IC50s of 450 nM and 622 nM, respectively[1][2]. PD-161570 is also a bone morphogenetic proteins (BMPs) and TGF-β signaling inhibitor[3].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

FGFR1:39.9 nM (IC50)

FGFR1:42 nM (Ki)

FGFR1 autophosphorylation:622 nM (IC50)

PDGFRβ:262 nM (IC50)

PDGFR:310 nM (IC50)

EGFR:240 nM (IC50)

c-Src:44 nM (IC50)

TGF-β Receptor

PD-161570 (Compound 6c; 0.1-1 µM; 1-8 days; VSMCs) treatment inhibits PDGF-stimulated vascular smooth muscle cell proliferation in a dose dependent fashion with an IC50 of 0.3 µM at day 8[1]. PD-161570 suppresses constitutive phosphorylation of the FGF-1 receptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth of A121(p) cells in culture[2]. PD-161570 can potent inhibit basic fibroblast growth factor (bFGF)-mediated angiogenesis[4]. Cell Proliferation Assay[1] Cell Line: Vascular smooth muscles cells (VSMCs) Concentration: 0.1 µM, 0.3 µM, 1 µM Incubation Time: 1 day, 3 days, 6 days, 8 days Result: Inhibited VSMC proliferation in a dose dependent fashion with an IC50 of 0.3 µM at day 8.

[1]. Hamby JM, et al. Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. J Med Chem. 1997 Jul 18;40(15):2296-303.

[2]. Batley BL, et al. Inhibition of FGF-1 receptor tyrosine kinase activity by PD 161570, a new protein-tyrosine kinase inhibitor. Life Sci. 1998;62(2):143-50.

[3]. Kyosuke Hino, et al. An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva. Stem Cell Reports. 2018 Nov 13;11(5):1106-1119.

[4]. Wolfe A, et al. Pharmacologic characterization of a kinetic in vitro human co-culture angiogenesis model using clinically relevant compounds. J Biomol Screen. 2013 Dec;18(10):1234-45.