PDGFRA/CAIX/XII-IN-1 is an inhibitor of PDGFRA, CA IX and CA XII, with an IC50 of 20 nM against PDGFRA, a K i of 93.3 nM against CA IX, and a K i of 80.0 nM against CA XII. PDGFRA/CAIX/XII-IN-1 binds to the ATP-binding pocket of PDGFRA and blocks the downstream STAT3, AKT and ERK1/2 signaling pathways. PDGFRA/CAIX/XII-IN-1 induces G0/G1 cell cycle arrest and endogenous apoptosis ( Apoptosis ), including cleavage of PARP-1, caspase-9 and caspase-3, activation of caspase 3/7, and down-regulation of Mcl-1. PDGFRA/CAIX/XII-IN-1 exhibits antiproliferative activity in eosinophilic leukemia cells. PDGFRA/CAIX/XII-IN-1 can be used for the research of leukemia [1].
In Vitro, PDGFRA/CAIX/XII-IN-1 (Compound 9d) potently inhibits recombinant PDGFRA protein, with an IC50 of 20 nM[1]. PDGFRA/CAIX/XII-IN-1 (1 μM) exerts targeted inhibitory effects on specific RTK subfamilies, and exhibits potent activity against PDGFRα and closely related class III RTKs[1]. PDGFRA/CAIX/XII-IN-1 inhibits recombinant human cancer-associated CA IX (Ki = 93.3 nM) and CA XII (Ki = 80.0 nM) with moderate potency, while exhibiting only weak activity against normal CA I/II isoforms[1]. PDGFRA/CAIX/XII-IN-1 (72 h) potently inhibits the proliferation of FIP1L1-PDGFRA-driven EOL-1 eosinophilic leukemia cells (GI50 = 2 nM), also exhibits significant cytotoxicity against MV4-11 cells (GI50 = 0.263 μM), and shows weak cytotoxicity against Kasumi-1 and RS4-11 cells with GI50 values of 2.081 μM and 4.599 μM, respectively[1]. PDGFRA/CAIX/XII-IN-1 (0-2500 nM; 1 h) dose-dependently inhibits the phosphorylation of FIP1L1-PDGFRA and its downstream STAT3, AKT and ERK1/2 signaling pathways in EOL-1 cells; after treatment at a concentration of 100 nM for 1 h, the inhibitory effect on PDGFRA is nearly complete[1]. PDGFRA/CAIX/XII-IN-1 (0-2500 nM; 24 h) induces apoptosis in EOL-1 eosinophilic leukemia cells by activating the intrinsic apoptotic pathway. The effect is detectable at a concentration of 0.8 nM, and the pathway is potently activated at subnanomolar concentrations, while no pro-apoptotic effect is observed on THP-1 cells[1]. PDGFRA/CAIX/XII-IN-1 (0.16-100 nM; 24 h) induces dose-dependent G0/G1 cell cycle arrest in EOL-1 eosinophilic leukemia cells, with a significant arrest effect observed at 0.8 nM; additionally, after 24 h of treatment, concentrations of 4 nM and above induce apoptotic cell death (characterized by a sub-G1 cell population)[1].
References:
[1]. Roshdy E, et al. First-in-Class Dual PDGFR/Carbonic Anhydrase IX/XII Inhibitors: 6,7-Dimethoxyquinoline-Sulfonamides as Promising Antileukemic Agents. J Med Chem. 2026;69(3):3115-3137.
In Vitro, PDGFRA/CAIX/XII-IN-1 (Compound 9d) potently inhibits recombinant PDGFRA protein, with an IC50 of 20 nM[1]. PDGFRA/CAIX/XII-IN-1 (1 μM) exerts targeted inhibitory effects on specific RTK subfamilies, and exhibits potent activity against PDGFRα and closely related class III RTKs[1]. PDGFRA/CAIX/XII-IN-1 inhibits recombinant human cancer-associated CA IX (Ki = 93.3 nM) and CA XII (Ki = 80.0 nM) with moderate potency, while exhibiting only weak activity against normal CA I/II isoforms[1]. PDGFRA/CAIX/XII-IN-1 (72 h) potently inhibits the proliferation of FIP1L1-PDGFRA-driven EOL-1 eosinophilic leukemia cells (GI50 = 2 nM), also exhibits significant cytotoxicity against MV4-11 cells (GI50 = 0.263 μM), and shows weak cytotoxicity against Kasumi-1 and RS4-11 cells with GI50 values of 2.081 μM and 4.599 μM, respectively[1]. PDGFRA/CAIX/XII-IN-1 (0-2500 nM; 1 h) dose-dependently inhibits the phosphorylation of FIP1L1-PDGFRA and its downstream STAT3, AKT and ERK1/2 signaling pathways in EOL-1 cells; after treatment at a concentration of 100 nM for 1 h, the inhibitory effect on PDGFRA is nearly complete[1]. PDGFRA/CAIX/XII-IN-1 (0-2500 nM; 24 h) induces apoptosis in EOL-1 eosinophilic leukemia cells by activating the intrinsic apoptotic pathway. The effect is detectable at a concentration of 0.8 nM, and the pathway is potently activated at subnanomolar concentrations, while no pro-apoptotic effect is observed on THP-1 cells[1]. PDGFRA/CAIX/XII-IN-1 (0.16-100 nM; 24 h) induces dose-dependent G0/G1 cell cycle arrest in EOL-1 eosinophilic leukemia cells, with a significant arrest effect observed at 0.8 nM; additionally, after 24 h of treatment, concentrations of 4 nM and above induce apoptotic cell death (characterized by a sub-G1 cell population)[1].
References:
[1]. Roshdy E, et al. First-in-Class Dual PDGFR/Carbonic Anhydrase IX/XII Inhibitors: 6,7-Dimethoxyquinoline-Sulfonamides as Promising Antileukemic Agents. J Med Chem. 2026;69(3):3115-3137.