SMI-4a

SMI-4a is a potent and selective Pim protein kinase inhibitor, which blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. 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 may be developed as a therapeutic strategy for the treatment of pre-T-LBL.

Product information

CAS Number: 438190-29-5

Molecular Weight: 273.23

Formula: C11H6F3NO2S

Chemical Name: 5-(3-(trifluoromethyl)benzylidene)thiazolidine-2,4-dione

Smiles: O=C1NC(=O)SC1=CC1=CC(=CC=C1)C(F)(F)F

InChiKey: NGJLOFCOEOHFKQ-VMPITWQZSA-N

InChi: InChI=1S/C11H6F3NO2S/c12-11(13,14)7-3-1-2-6(4-7)5-8-9(16)15-10(17)18-8/h1-5H,(H,15,16,17)/b8-5+

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: 10 mM in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Incubation of pre-T-LBL cells with (Z)-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 (Z)-SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of (Z)-SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. Ectopic expression of phosphomimetic mutants of eIF4B conferred resistance to apoptosis by the Pim kinase inhibitor (Z)-SMI-4a in Abl-transformed cells .

In Vivo:

In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with (Z)-SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries .

References:

1. Lin YW, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010 ;115(4):824-33.
2. Yang J, et al. eIF4B phosphorylation by pim kinases plays a critical role in cellular transformation by Abl oncogenes. Cancer Res. 2013 Aug 1;73(15):4898-908.

Products are for research use only. Not for human use.