438190-29-5

Basic information

• Product Name: (5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione
• Synonyms: (5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione;TCS PIM-1 4a;SMI-4a;(Z)-5-(3-(trifluoroMethyl)benzylidene)thiazolidine-2,4-dione;2,4-Thiazolidinedione, 5-[[3-(trifluoromethyl)phenyl]methylene]-, (5Z)-;TCS PIM-1 4a, >=98%;(5E)-5-{[3-(trifluoromethyl)phenyl]methylidene}-1,3-thiazolidine-2,4-dione;(Z)-SMI-4a
• CAS NO: 438190-29-5
• Molecular Formula: C₁₁H₆F₃NO₂S
• Molecular Weight: 273
• Product Categories: Inhibitor;Inhibitors;JAK;STAT
• Mol File: 438190-29-5.mol
• Article Data: 2

Chemical Properties

• Appearance: white to beige/
• Storage Temp.: Desiccate at +4°C
• Solubility: DMSO: >10mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• CAS DataBase Reference: (5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione(CAS DataBase Reference)
• NIST Chemistry Reference: (5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione(438190-29-5)
• EPA Substance Registry System: (5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione(438190-29-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36-43
• Safety Statements: 26-36/37
• WGK Germany: 3
• Hazardous Substances Data: 438190-29-5(Hazardous Substances Data)

Usage

Description

(5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione, also known as SMI-4a, is a selective, ATP-competitive inhibitor of the Pim protein kinases with an IC50 of 24 nM for Pim-1 and 100 nM for Pim-2. It is selective over a panel of approximately 50 other kinases and has the ability to induce cell cycle arrest in leukemia and prostate cancer cells. SMI-4a is also a cell-permeable compound and a useful tool for exploring the involvement of Pim in cellular signaling.

Uses

Used in Cancer Research:
(5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione is used as a research tool for studying the role of Pim protein kinases in cancer cell growth and proliferation. Its ability to selectively inhibit Pim kinases makes it a valuable compound for investigating the underlying mechanisms of cancer development and progression.
Used in Drug Development:
(5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione is used as a potential therapeutic agent in the inhibition and treatment of cancer and cancer cell lines. Its dual functionality as an aldose reductase inhibitor and a COX-2 inhibitor suggests that it may have potential applications in the development of novel cancer therapies.
Used in Pharmaceutical Industry:
(5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione is used as a lead compound in the development of new drugs targeting Pim protein kinases. Its selectivity and potency make it a promising candidate for further optimization and development into a clinically relevant drug.
Used in Academic Research:
(5Z)-5-[[3-(Trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione is used as a research compound in academic institutions to study the molecular mechanisms of Pim kinases in various cellular processes, including cell cycle regulation, apoptosis, and cell survival. This knowledge can contribute to a better understanding of the role of Pim kinases in cancer and other diseases.

References

1) Xia et al. (2009), Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases; J. Med. Chem., 52 74 2) Beharry et al. (2009), Novel benzylidene-thiazolidine-2,4-diones inhibit Pim protein kinase activity and induce cell cycle arrest in leukemia and prostate cancer cells; Mol. Cancer Ther., 8 1473 3) Lin et al. (2010), A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma; Blood, 115 824 4) Zhang et al. (2009), PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells; Cancer Biol. Ther., 8 846

Upstream product

• 2295-31-0 thiazoline-2,4-dione 
• 454-89-7 3-Trifluoromethylbenzaldehyde 

Downstream Products

• 438190-38-6 {2,4-Dioxo-5-[1-(3-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-thiazolidin-3-yl}-acetic acid methyl ester 

Relevant articles and documents

Synthesis and evaluation of novel inhibitors of pim-1 and pim-2 protein kinases

The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. 5-(3-Trifluoromethylbenzylidene) thiazolidine-2,4-dione (4a) was identified by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although 4a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. Computational docking of 4a to Pim-1 provided a model for lead optimization, and a series of substituted thiazolidine-2,4-dione congeners was synthesized. The most potent new compounds exhibited IC 50s of 13 nM for Pim-1 and 2.3 μM for Pim-2. Additional compounds in the series demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim- 2, respectively, while other congeners were essentially equally potent toward the two isozymes. Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel anticancer agents.