PDGFR Inhibitor

Lenvatinib (E7080) is an oral, multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET, shows potent antitumor activities.

Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC₅₀s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.

Imatinib (STI571) is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity. Imatinib (STI571) works by binding close to the ATP binding site, locking it in a closed or self-inhibited conformation, therefore inhibiting the enzyme activity of the protein semicompetitively. Imatinib also is an inhibitor of SARS-CoV and MERS-CoV.

Sunitinib (SU 11248) is a multi-targeted receptor tyrosine kinase inhibitor with IC₅₀s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively. Sunitinib, an ATP-competitive inhibitor, effectively inhibits autophosphorylation of Ire1α by inhibiting autophosphorylation and consequent RNase activation.

Regorafenib (BAY 73-4506) is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC₅₀ values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib shows very robust antitumor and antiangiogenic activity.

GW296115 is a multi-target inhibitor with the following IC₅₀ values against its targets: 8.4 nM for BRSK2, 21 nM for BRSK1, 1.8 μM for PDGFRβ, 5.5 nM for STK17B/DRAK2, 28 nM for DRAK1, 20 nM for PHKG1, and 89 nM for DCAMKL3. GW296115 downregulates the phosphorylation of S317 site on ULK1 and S351 site on P62, which are AMPK substrates driven by BRSK2. GW296115 does not alter the phosphorylation level of AMPK at T172, reduces nutrient deprivation-mediated Autophagy and autophagosome formation, and enhances Apoptosis. GW296115 exhibits anticancer activity against triple-negative breast cancer. GW296115 is applicable for breast cancer-related research.

Pegpleranib (Fovista) sodium is a pegylated DNA aptamer that selectively binds to PDGF-BB and PDGF-AB homodimers and heterodimers, interrupting the interaction with their associated tyrosine kinase receptors.

SNX-7081 is an Hsp90 inhibitor with K_i and IC₅₀ values of 26 nM and 44 nM, respectively. SNX-7081 blocks the nuclear translocation of NF-κB, inhibits the production of pro-inflammatory cytokines, attenuates the ERK/JNK and PDGF signaling pathways, and suppresses LPS (HY-D1056)-induced nitric oxide production. SNX-7081 inhibits DNA repair, induces G₂/M cell cycle arrest, and triggers apoptosis via downregulation of MYC/nucleolin and activation of Fas. SNX-7081 can be used in research related to rheumatoid arthritis and cancer.

Ponatinib (AP24534) is an orally active multi-targeted kinase inhibitor with IC₅₀s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.

Axitinib is a multi-targeted tyrosine kinase inhibitor with IC₅₀s of 0.1, 0.2, 0.1-0.3, 1.6 nM for VEGFR1, VEGFR2, VEGFR3 and PDGFRβ, respectively.

Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC₅₀s of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.

Avapritinib (BLU-285) is a highly potent, selective, and orally active KIT and PDGFRA activation loop mutant kinases inhibitor with IC₅₀s of 0.27 and 0.24 nM for KIT D816V and PDGFRA D842V, respectively. Avapritinib (BLU-285) binds the active conformation of the kinase and shows antitumor activity. Avapritinib (BLU-285) attenuates the transport function of both ABCB1 and ABCG2.

SU 5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC₅₀ of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGFRβ, respectively.

Nintedanib esylate (BIBF 1120 esylate) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC₅₀s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.

Lenvatinib mesylate (E7080 mesylate), an oral, multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET, shows potent antitumor activities.

CP-673451 is a potent and selective inhibitor of PDGFR with IC₅₀s of 10 and 1 nM for PDGFRα and PDGFRβ, respectively.

Imatinib Mesylate (STI571 Mesylate) is an orally active tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC₅₀=100 nM) tyrosine kinases.

Crenolanib is a potent and selective inhibitor of wild-type and mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β with K_ds of 0.74 nM and 2.1 nM/3.2 nM, respectively.

Sunitinib (SU 11248) Malat is a multi-targeted receptor tyrosine kinase inhibitor with IC₅₀s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively. Sunitinib Malat, an ATP-competitive inhibitor, effectively inhibits autophosphorylation of Ire1α by inhibiting autophosphorylation and consequent RNase activation.

Ripretinib (DCC-2618) is an orally bioavailable, selective KIT and PDGFRA switch-control inhibitor. Ripretinib (DCC-2618) targets and binds to both wild-type and mutant forms of KIT and PDGFRA specifically at their switch pocket binding sites, thereby preventing the switch from inactive to active conformations of these kinases and inactivating their wild-type and mutant forms. Ripretinib (DCC-2618) also inhibits multiple other kinase targets, such as FLT3 and KDR (or VEGFR-2). DCC-2618 exerts antineoplastic effect and induces apoptosis.