Gilteritinib (4 (link)) (ASP2215; Active Biochem, Maplewood, NJ) and quizartinib (4 (link)) (AC220; Selleck Chemicals, Houston, TX), type I and II FLT3 inhibitors, respectively, clinically active in FLT3-ITD AML, were used at pharmacologically relevant concentrations (23 (link),24 (link)). The SET-sequestering PAD FTY720 (25 (link)) (Fingolimod; Cayman Chemical Company, Ann Arbor, MI) was also used at pharmacologically relevant concentrations. DT-061, an orally bioavailable small molecule activator of PP2A (SMAP) developed by reengineering tricyclic neuroleptics and proposed to directly bind the PP2A Aα subunit (26 (link)–29 (link)), was provided by Dr. Goutham Narla. The pan-Pim inhibitor AZD1208 and GSK-3β inhibitors TC-G 24 and TWS119 were from Tocris Bioscience, Minneapolis, MN, the c-Myc inhibitor 10058-F4 from Sigma-Aldrich, and the pan-AKT inhibitor MK-2206 from Selleck Chemicals, Houston, TX.
Tc g 24
Manufactured by Bio-Techne
The TC-G 24 is a laboratory equipment product designed for sample incubation and temperature control. It provides a controlled environment for various applications in biological research and analysis.
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2 protocols using tc g 24
1
Inhibitors of FLT3, PP2A, and Signaling Pathways in AML
2
FLT3, Pim, and GSK-3β Inhibitors
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The FLT3 inhibitor gilteritinib (ASP2215; MedChemExpress, #HY-12432) was used at clinically relevant (29 (link)) concentrations of 10 or 15 nmol/L in in vitro experiments, consistent with concentrations that inhibited FLT3 and STAT5 inhibition in cells with FLT3-ITD (30, 31 (link)) and IC50 concentrations in cells with FLT3-ITD (24, 30, 31 (link)) and concentrations used in vitro in prior literature (24, 30, 31 (link)). The pan-Pim inhibitor AZD1208 (Tocris Bioscience, #6310) and Pim-1 inhibitor TP-3654 (MedChemExpress, #HY-101126) were both used at 1 µmol/L based on inhibition of p-BAD (S112) at this concentration (32, 33 (link)). The GSK-3β inhibitor TC-G 24 (Tocris, #4353) was used at 17 nmol/L based on GSK-3β inhibition (24 (link)).
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