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Chemical Structure| 1448428-04-3 Chemical Structure| 1448428-04-3

Structure of Selonsertib
CAS No.: 1448428-04-3

Chemical Structure| 1448428-04-3

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Selonsertib (GS-4997), an orally bioavailable and selective apoptosis signal-regulating kinase 1 (ASK1) inhibitor with a pIC50 of 8.3, has been studied as a potential treatment for diabetic nephropathy and kidney fibrosis.

Synonyms: GS-4997; GS-4977

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Product Details of Selonsertib

CAS No. :1448428-04-3
Formula : C24H24FN7O
M.W : 445.49
SMILES Code : O=C(C1=CC(N2C=C(N=C2)C3CC3)=C(C=C1F)C)NC4=NC(C5=NN=CN5C(C)C)=CC=C4
Synonyms :
GS-4997; GS-4977
MDL No. :MFCD29920355
InChI Key :YIDDLAAKOYYGJG-UHFFFAOYSA-N
Pubchem ID :71245288

Safety of Selonsertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Selonsertib

MAPK

Isoform Comparison

Biological Activity

Target
  • ASK1

    ASK1, pIC50:8.3

In Vitro:

Cell Line
Concentration Treated Time Description References
Neonatal rat cardiomyocytes 1 μMol/L 5 minutes Selonsertib selectively inhibited H2O2-induced p38-MAPK activation but not JNKs. PMC7480944
Neonatal rat cardiomyocytes 25 ng/mL 15 minutes IL-1β activated TAK1 but not ASK1. PMC7480944
LO2 cells 10–0.3 μmol/L 72 hours CS17919 significantly prevented apoptosis at all doses while GS-4997 only protected against cell death at lower doses. Surprisingly, at 5 and 10 μmol/L GS-4997 reduced cell viability in a dose-dependent manner, while CS17919 exhibited a mild protective effect at both doses. PMC10808927
HEK-293A cells 0.3–10 μmol/L 72 hours CS17919 barely affected cell viability, while GS-4997 reduced cell viability at higher doses. PMC11798738
HUH7 cells 0.3–10 μmol/L 72 hours CS17919 barely affected cell viability, while GS-4997 reduced cell viability at higher doses. PMC11798738
CCC-HEL-1 cells 0.3–10 μmol/L 72 hours CS17919 barely affected cell viability, while GS-4997 reduced cell viability at higher doses. PMC11798738
MRC-5 cells 0.3–10 μmol/L 72 hours CS17919 barely affected cell viability, while GS-4997 reduced cell viability at higher doses. PMC11798738

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice High-fat diet-induced NASH model Oral gavage 1 mg/kg Single dose, observed at various time points The combination of Selonsertib and Pioglitazone significantly improved liver injury in high-fat diet-induced NASH mice, reducing steatosis, fibrosis, and hepatocellular death. PMC8220246
Mice Bleomycin-induced pulmonary fibrosis model Oral gavage 33 mg/kg Twice daily, 5 days/week for 2 weeks Treatment with the ASK1 inhibitor Selonsertib during the fibrotic phase showed that pharmacological inhibition of ASK1 reduced activation of ASK1, p38, and ERK1/2 and promoted the restoration of redox and EMT indicators, as well as improvements in histological parameters. PMC9116360
C57BL/6J mice Ang II-induced hypertension model Osmotic minipump 20 mg/kg Once daily for 14 days Selonsertib suppressed Ang II-induced cardiac hypertrophy and significantly reduced interstitial and perivascular fibrosis. PMC7480944
mice UUO model oral 35 mg/kg Once daily for 15 days GS-4997 significantly reduced serum urea nitrogen and showed a tendency to decrease serum creatinine. PMC11798738

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02509624 Diabetic Kidney Disease PHASE1 COMPLETED 2015-12-15 Denver, Colorado, United State... More >>s|Miami, Florida, United States|Orlando, Florida, United States|Minneapolis, Minnesota, United States|San Antonio, Texas, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.24mL

0.45mL

0.22mL

11.22mL

2.24mL

1.12mL

22.45mL

4.49mL

2.24mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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