SMI-4a
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MedKoo CAT#: 407121

CAS#: 438190-29-5

Description: 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.


Chemical Structure

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SMI-4a
CAS# 438190-29-5

Theoretical Analysis

MedKoo Cat#: 407121
Name: SMI-4a
CAS#: 438190-29-5
Chemical Formula: C11H6F3NO2S
Exact Mass: 273.01
Molecular Weight: 273.230
Elemental Analysis: C, 48.36; H, 2.21; F, 20.86; N, 5.13; O, 11.71; S, 11.73

Price and Availability

Size Price Availability Quantity
100mg USD 90 Ready to ship
200mg USD 150 Ready to ship
500mg USD 330 Ready to ship
1g USD 550 Ready to ship
2g USD 950 Ready to ship
5g USD 2150 Ready to ship
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Synonym: SMI-4a; SMI4a; SMI 4a; TCS PIM-1 4a.

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

InChi Key: NGJLOFCOEOHFKQ-VMPITWQZSA-N

InChi Code: 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+

SMILES Code: O=C(NC/1=O)SC1=C\C2=CC=CC(C(F)(F)F)=C2

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: SMI-4a is a Pim-1 inhibitor (IC50 = 24μM and Ki = 0.6μM). SMI-4a also inhibits Pim-2 (IC50 = 100μM), and does not significantly inhibit the other serine/threonine- or tyrosine-kinases. SIM-4a kills a wide range of both myeloid and lymphoid cell lines (IC50s = 0.8 to 40μM).
In vitro activity: SMI-4a shows promise in treating chronic myeloid leukemia (CML), especially in combination with existing chemotherapeutics, for imatinib-resistant CML. It inhibits cell proliferation, induces apoptosis, and reduces colony formation in K562 and imatinib-resistant K562 cell lines. SMI-4a impacts key signaling pathways, decreasing p-Ser9-GSK3β, inhibiting β-catenin translocation, and modulating gene expression related to apoptosis. Reference: Mol Med Rep. 2017 Oct;16(4):4603-4612. https://pubmed.ncbi.nlm.nih.gov/28849186/
In vivo activity: SMI-4a could be a promising therapy for LPS-induced acute lung injury (ALI)by reducing cytokine production through inhibiting p65 activities. In an LPS-induced ALI murine model, SMI-4a improved survival rates, reduced lung edema severity, and decreased inflammatory cell counts. It also suppressed cytokine production in cells and lung fluid. SMI-4a mitigated nuclear p65 and phosphorylated p65 levels. Reference: Int Immunopharmacol. 2019 Aug;73:568-574. https://pubmed.ncbi.nlm.nih.gov/31203114/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 109.80
DMSO 30.0 109.80
Ethanol 30.0 109.80

Preparing Stock Solutions

The following data is based on the product molecular weight 273.23 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Fan RF, Lu Y, Fang ZG, Guo XY, Chen YX, Xu YC, Lei YM, Liu KF, Lin DJ, Liu LL, Liu XF. PIM-1 kinase inhibitor SMI-4a exerts antitumor effects in chronic myeloid leukemia cells by enhancing the activity of glycogen synthase kinase 3β. Mol Med Rep. 2017 Oct;16(4):4603-4612. doi: 10.3892/mmr.2017.7215. Epub 2017 Aug 10. PMID: 28849186; PMCID: PMC5647015. 2. Xia Z, Knaak C, Ma J, Beharry ZM, McInnes C, Wang W, Kraft AS, Smith CD. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. 2009 Jan 8;52(1):74-86. doi: 10.1021/jm800937p. PMID: 19072652; PMCID: PMC5404933. 3. Zhang Z, Xie S, Qian J, Gao F, Jin W, Wang L, Yan L, Chen H, Yao W, Li M, Wang X, Zhu L. Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway. J Transl Med. 2023 Jul 8;21(1):452. doi: 10.1186/s12967-023-04313-1. PMID: 37422640; PMCID: PMC10329339. 4. Wang J, Cao Y, Liu Y, Zhang X, Ji F, Li J, Zou Y. PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. Int Immunopharmacol. 2019 Aug;73:568-574. doi: 10.1016/j.intimp.2019.05.040. Epub 2019 Jun 13. PMID: 31203114.
In vitro protocol: 1. Fan RF, Lu Y, Fang ZG, Guo XY, Chen YX, Xu YC, Lei YM, Liu KF, Lin DJ, Liu LL, Liu XF. PIM-1 kinase inhibitor SMI-4a exerts antitumor effects in chronic myeloid leukemia cells by enhancing the activity of glycogen synthase kinase 3β. Mol Med Rep. 2017 Oct;16(4):4603-4612. doi: 10.3892/mmr.2017.7215. Epub 2017 Aug 10. PMID: 28849186; PMCID: PMC5647015. 2. Xia Z, Knaak C, Ma J, Beharry ZM, McInnes C, Wang W, Kraft AS, Smith CD. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. 2009 Jan 8;52(1):74-86. doi: 10.1021/jm800937p. PMID: 19072652; PMCID: PMC5404933.
In vivo protocol: 1. Zhang Z, Xie S, Qian J, Gao F, Jin W, Wang L, Yan L, Chen H, Yao W, Li M, Wang X, Zhu L. Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway. J Transl Med. 2023 Jul 8;21(1):452. doi: 10.1186/s12967-023-04313-1. PMID: 37422640; PMCID: PMC10329339. 2. Wang J, Cao Y, Liu Y, Zhang X, Ji F, Li J, Zou Y. PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. Int Immunopharmacol. 2019 Aug;73:568-574. doi: 10.1016/j.intimp.2019.05.040. Epub 2019 Jun 13. PMID: 31203114.

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1: Cervantes-Gomez F, Lavergne B, Keating MJ, Wierda WG, Gandhi V. Combination of Pim kinase inhibitors and Bcl-2 antagonists in chronic lymphocytic leukemia cells. Leuk Lymphoma. 2015 Jun 19:1-23. [Epub ahead of print] PubMed PMID: 26088877.

2: Yang J, Wang J, Chen K, Guo G, Xi R, Rothman PB, Whitten D, Zhang L, Huang S, Chen JL. eIF4B phosphorylation by pim kinases plays a critical role in cellular transformation by Abl oncogenes. Cancer Res. 2013 Aug 1;73(15):4898-908. doi: 10.1158/0008-5472.CAN-12-4277. Epub 2013 Jun 7. PubMed PMID: 23749639.

3: Beharry Z, Mahajan S, Zemskova M, Lin YW, Tholanikunnel BG, Xia Z, Smith CD, Kraft AS. The Pim protein kinases regulate energy metabolism and cell growth. Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):528-33. doi: 10.1073/pnas.1013214108. Epub 2010 Dec 27. PubMed PMID: 21187426; PubMed Central PMCID: PMC3021022.

4: Lin YW, Beharry ZM, Hill EG, Song JH, Wang W, Xia Z, Zhang Z, Aplan PD, Aster JC, Smith CD, Kraft AS. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010 Jan 28;115(4):824-33. doi: 10.1182/blood-2009-07-233445. Epub 2009 Nov 23. PubMed PMID: 19965690; PubMed Central PMCID: PMC2941996.