Raw material Selonsertib

Selonsertib More Info

Selonsertib (formerly known as GS-4997) is a selective, orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with potential anti-inflammatory, anti-tumor, and anti-fibrotic activities. Its CAS number is 1448428-04-3 .

Mechanism of Action

ASK1 is a member of the MAP3K family and serves as a key signaling node that responds to cellular stress, being activated particularly under oxidative stress, endoplasmic reticulum stress, or inflammatory signaling, leading to inflammation, apoptosis, and fibrosis .

Selonsertib is a highly selective and potent ASK1 inhibitor that competitively inhibits ATP in the catalytic kinase domain of ASK1 . By binding the ATP-binding site of ASK1, it prevents the phosphorylation of its downstream targets such as p38 and JNK, thereby interrupting inflammatory, apoptotic, and hepatic stellate cell activation signaling pathways . It achieves this by inhibiting the production of inflammatory cytokines, down-regulating fibrosis-related gene expression, suppressing excessive apoptosis, and inhibiting cell proliferation.

In vitro studies confirm that Selonsertib inhibits ASK1 and its downstream p38/JNK MAPK signaling, thereby suppressing the expression of α-SMA, collagen I, and fibronectin.

Chemical Properties

Chemical Formula: C₂₄H₂₄FN₇O

Molecular Weight: 445.49

CAS Number: 1448428-04-3

Purity: ≥98%

pIC₅₀: 8.3

Solubility: ≥44.5 mg/mL in DMSO, ≥88.8 mg/mL in ethanol, insoluble in water

Chemical Name: 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylaniline

Therapeutic Applications

Selonsertib is being studied for the treatment of fibrotic and inflammatory diseases such as non-alcoholic steatohepatitis (NASH), diabetic kidney disease (DKD), and pulmonary fibrosis. It is being investigated in clinical trial NCT03053050 for its safety and efficacy in treating NASH and fibrosis.

In in vivo studies, Selonsertib effectively reduced cardiac hypertrophy and fibrosis in mouse models, including in an angiotensin II (Ang II)-induced hypertensive model.

Storage & Handling

Selonsertib should be stored as a powder at -20°C (shelf life up to 3 years), and stored at -80°C after dissolution . It is intended for research use only and is not approved for diagnostic or therapeutic use in humans or animals.