TCS-PIM-1-4a

TCS-PIM-1-4a is a Pim inhibitor that blocks mTORC1 activity via activation of AMPK; kills a wide range of both myeloid and lymphoid cell lines (with IC50 values ranging from 0.8 to 40 μM).IC50 value:Target: Pim SMI-4a a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. SMI-4a blocked the rapamycin-sensitive mTORC1 activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK).

Signaling Pathways >> JAK/STAT Signaling >> Pim

Research Areas >> Cancer

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AZD1208 | PIM-447 dihydrochloride | Pim1/AKK1-IN-1 | SGI-1776 free base | CX-6258 | TP-3654 | Hispidulin | TCS PIM-1 1 | GDC-0339 | SMI-16a | SMI-4a | M-110 | INCB053914 phosphate | 3,3',4',5,6,7-HEXAHYDROXYFLAVONE