SMI-4a | TCS PIM-1 4a | CAS#438190-29-5 | PIM inhibitor

MedKoo Cat#: 407121 | Name: SMI-4a

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

SMI-4a

CAS#438190-29-5

Theoretical Analysis

MedKoo Cat#: 407121

Name: SMI-4a

CAS#: 438190-29-5

Chemical Formula: C11H6F3NO2S

Exact Mass: 273.0071

Molecular Weight: 273.23

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
100mg	USD 90.00	Ready to ship
200mg	USD 150.00	Ready to ship
500mg	USD 330.00	Ready to ship
1g	USD 550.00	Ready to ship
2g	USD 950.00	Ready to ship
5g	USD 2,150.00	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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC60817

QC Data

View QC data: current batch, Lot#SSC60817

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	109.80
	DMSO	30.0	109.80
	Ethanol	30.0	109.80

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Garnish SE, Horne CR, Meng Y, Young SN, Jacobsen AV, Hildebrand JM, Murphy JM. Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation. Biochem J. 2024 Sep 4;481(17):1125-1142. doi: 10.1042/BCJ20240255. PMID: 39136677. 2: Wu X, Chen Y, Jiang M, Guo L. PIM1 inhibitor SMI-4a attenuated concanavalin A-induced acute hepatitis through suppressing inflammatory responses. Transl Gastroenterol Hepatol. 2024 Mar 22;9:14. doi: 10.21037/tgh-23-93. PMID: 38716217; PMCID: PMC11074483. 3: Manupati K, Hao M, Haas M, Yeo SK, Guan JL. Role of NuMA1 in breast cancer stem cells with implications for combination therapy of PIM1 and autophagy inhibition in triple negative breast cancer. Res Sq [Preprint]. 2024 Apr 1:rs.3.rs-3953289. doi: 10.21203/rs.3.rs-3953289/v1. PMID: 38645153; PMCID: PMC11030541. 4: Park YS, Kim J, Ryu YS, Moon JH, Shin YJ, Kim JH, Hong SW, Jung SA, Lee S, Kim SM, Lee DH, Kim DY, Yun H, You JE, Yoon DI, Kim CH, Koh DI, Jin DH. Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer. Cancer Biol Ther. 2023 Dec 31;24(1):2246208. doi: 10.1080/15384047.2023.2246208. PMID: 37621144; PMCID: PMC10461515. 5: 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. 6: Wang M, Fan R, Jiang J, Sun F, Sun Y, Wang Q, Jiang A, Yu Z, Yang T. PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis. Reprod Sci. 2023 Sep;30(9):2692-2702. doi: 10.1007/s43032-023-01208-w. Epub 2023 Apr 14. PMID: 37059967. 7: Yuan K, Ji M, Xie S, Qiu Z, Chen W, Min W, Xia F, Zheng M, Wang X, Li J, Hou Y, Kuang W, Wang L, Gu W, Li Z, Yang P. Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia. J Med Chem. 2022 Jan 13;65(1):857-875. doi: 10.1021/acs.jmedchem.1c02019. Epub 2021 Dec 27. Erratum in: J Med Chem. 2022 May 12;65(9):6969-6970. doi: 10.1021/acs.jmedchem.2c00603. PMID: 34958208. 8: Wang Y, Xiu J, Ren C, Yu Z. Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics. J Cancer. 2021 Mar 5;12(9):2570-2581. doi: 10.7150/jca.53134. PMID: 33854618; PMCID: PMC8040705. 9: Ma Y, Li T, Feng R, Guo G, Pan Q, Li J, Chen J. [Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia]. Sheng Wu Gong Cheng Xue Bao. 2020 Nov 25;36(11):2413-2423. Chinese. doi: 10.13345/j.cjb.200015. PMID: 33244935. 10: Cao Y, Chen X, Liu Y, Zhang X, Zou Y, Li J. PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells. Inflamm Res. 2021 Jan;70(1):89-98. doi: 10.1007/s00011-020-01420-3. Epub 2020 Nov 13. PMID: 33185705. 11: Zhang X, Zou Y, Liu Y, Cao Y, Zhu J, Zhang J, Chen X, Zhang R, Li J. Inhibition of PIM1 kinase attenuates bleomycin-induced pulmonary fibrosis in mice by modulating the ZEB1/E-cadherin pathway in alveolar epithelial cells. Mol Immunol. 2020 Sep;125:15-22. doi: 10.1016/j.molimm.2020.06.013. Epub 2020 Jun 30. Erratum in: Mol Immunol. 2024 Jul;171:115-116. doi: 10.1016/j.molimm.2024.04.014. PMID: 32619930. 12: Yang T, Ren C, Lu C, Qiao P, Han X, Wang L, Wang D, Lv S, Sun Y, Yu Z. Phosphorylation of HSF1 by PIM2 Induces PD-L1 Expression and Promotes Tumor Growth in Breast Cancer. Cancer Res. 2019 Oct 15;79(20):5233-5244. doi: 10.1158/0008-5472.CAN-19-0063. Epub 2019 Aug 13. PMID: 31409638. 13: Han X, Ren C, Yang T, Qiao P, Wang L, Jiang A, Meng Y, Liu Z, Du Y, Yu Z. Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene. 2019 Sep;38(38):6537-6549. doi: 10.1038/s41388-019-0898-z. Epub 2019 Jul 29. PMID: 31358902. 14: 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. 15: Jiang W, Chen Y, Song X, Shao Y, Ning Z, Gu W. Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway. Onco Targets Ther. 2019 Apr 23;12:3043-3050. doi: 10.2147/OTT.S203142. PMID: 31114247; PMCID: PMC6497832. 16: Kuang X, Xiong J, Wang W, Li X, Lu T, Fang Q, Wang J. PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway. Life Sci. 2019 Feb 15;219:248-256. doi: 10.1016/j.lfs.2019.01.022. Epub 2019 Jan 16. PMID: 30658101. 17: Yang T, Ren C, Qiao P, Han X, Wang L, Lv S, Sun Y, Liu Z, Du Y, Yu Z. PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer. Oncogene. 2018 Nov;37(45):5997-6009. doi: 10.1038/s41388-018-0386-x. Epub 2018 Jul 9. Erratum in: Oncogene. 2020 Jan;39(3):720-721. doi: 10.1038/s41388-019-0982-4. PMID: 29985480; PMCID: PMC6224402. 18: Lv DL, Chen L, Ding W, Zhang W, Wang HL, Wang S, Liu WB. Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death. Chin Med. 2018 Feb 21;13:11. doi: 10.1186/s13020-018-0168-y. PMID: 29483938; PMCID: PMC5820787. 19: Fujii S, Nakamura S, Oda A, Miki H, Tenshin H, Teramachi J, Hiasa M, Bat- Erdene A, Maeda Y, Oura M, Takahashi M, Iwasa M, Endo I, Yoshida S, Aihara KI, Kurahashi K, Harada T, Kagawa K, Nakao M, Sano S, Abe M. Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity. Br J Haematol. 2018 Jan;180(2):246-258. doi: 10.1111/bjh.15033. PMID: 29327347. 20: 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.