SB 431542
[CAS# 301836-41-9]

Identification

• Classification: Biochemical >> Inhibitor >> TGF-beta/Smad signaling pathway inhibitor (TGF-beta/Smad) >> TGF-beta/Smad inhibitor
• Name: SB 431542
• Synonyms: 4-[4-(3,4-Methylenedioxyphenyl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzamide
• Molecular Formula: C₂₂H₁₆N₄O₃
• Molecular Weight: 384.39
• CAS Registry Number: 301836-41-9
• SMILES: C1OC2=C(O1)C=C(C=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 662.4±55.0 °C 760 mmHg (Calc.)^*
• Flash point: 354.4±31.5 °C (Calc.)^*
• Solubility: Soluble in DMSO (100mM) and ethanol (10mM) (Expl.)
• Index of refraction: 1.68 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

SB 431542 is a synthetic small-molecule inhibitor primarily targeting the transforming growth factor-beta (TGF-β) type I receptors, including activin receptor-like kinase 5 (ALK5), ALK4, and ALK7. It was discovered during efforts to identify selective inhibitors of TGF-β signaling, which plays a crucial role in various cellular processes such as proliferation, differentiation, apoptosis, and extracellular matrix production.

The discovery of SB 431542 provided a valuable chemical tool to study the complex TGF-β signaling pathway, which is involved in normal physiological regulation as well as pathological conditions like fibrosis, cancer progression, and immune system disorders. By selectively inhibiting the kinase activity of TGF-β type I receptors, SB 431542 effectively blocks downstream signaling mediated by Smad proteins, thereby modulating gene expression controlled by TGF-β.

SB 431542 has found broad applications in biomedical research, especially in studies focused on understanding TGF-β's role in disease mechanisms. It is widely used to explore the regulation of epithelial-to-mesenchymal transition (EMT), a process involved in cancer metastasis and organ fibrosis. By preventing TGF-β–induced EMT, SB 431542 helps elucidate therapeutic strategies to control tumor invasion and fibrotic tissue remodeling.

Additionally, SB 431542 is employed in stem cell biology to maintain pluripotency and direct differentiation by modulating TGF-β signaling pathways. It has been used to improve protocols for generating induced pluripotent stem cells (iPSCs) and in directing stem cell fate decisions during development and tissue regeneration research.

Pharmacologically, SB 431542 exhibits high specificity for its targets, with minimal off-target effects at commonly used concentrations. This selectivity makes it a preferred compound for in vitro experiments aimed at dissecting TGF-β–related cellular functions without broadly affecting other kinase pathways.

The compound is typically applied in cell culture studies and experimental models of disease to investigate the consequences of TGF-β pathway inhibition. Its use has contributed to a deeper understanding of the molecular mechanisms underlying fibrosis, cancer biology, immune modulation, and developmental processes, making it a critical reagent in drug discovery and therapeutic research.

In summary, SB 431542 is a key research compound discovered as a selective inhibitor of TGF-β type I receptors. Its ability to modulate a pivotal signaling pathway has made it indispensable in various fields of biomedical research, particularly in studying disease mechanisms related to fibrosis, cancer, and stem cell biology. Its application continues to aid in the development of potential therapeutic interventions targeting TGF-β signaling.

References

2002. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molecular Pharmacology, 62(1).
DOI: 10.1124/mol.62.1.65

2005. SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts. Journal of Dermatological Science, 39(1).
DOI: 10.1016/j.jdermsci.2005.01.013

2024. SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells. Cell Communication and Signaling, 22(1).
DOI: 10.1186/s12964-023-01372-1