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Chemical Structure| 254740-64-2 Chemical Structure| 254740-64-2

Structure of Sparsentan
CAS No.: 254740-64-2

Chemical Structure| 254740-64-2

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Sparsentan is a dual antagonist that acts on both angiotensin II and endothelin A receptors, holding potential for application in the treatment of hypertension and cardiovascular diseases.

Synonyms: RE-021; DARA-a; DARA

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Product Details of Sparsentan

CAS No. :254740-64-2
Formula : C32H40N4O5S
M.W : 592.75
SMILES Code : O=S(C1=CC=CC=C1C2=CC=C(CN3C(CCCC)=NC4(CCCC4)C3=O)C=C2COCC)(NC5=NOC(C)=C5C)=O
Synonyms :
RE-021; DARA-a; DARA
MDL No. :MFCD16628036
InChI Key :WRFHGDPIDHPWIQ-UHFFFAOYSA-N
Pubchem ID :10257882

Safety of Sparsentan

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P233-P260-P261-P264-P270-P271-P280-P301+P312-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P330-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501

Related Pathways of Sparsentan

GPCR

Isoform Comparison

Biological Activity

Description
Sparsentan (RE-021) stands out as a potent dual antagonist for both angiotensin II and endothelin A receptors, with inhibition constants (Kis) of 0.8 and 9.3 nM respectively[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Pituitary GH3 cells 0.3–100 μM 40 ms Sparsentan differentially inhibited the peak and late components of voltage-gated Na+ current (INa). The IC50 values for peak and late INa were 15.04 μM and 1.21 μM, respectively. PMC8773265

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice FSGS, DKD, LN models Oral 30 mmol/kg Three times weekly Sparsentan reduces CD8+ TRM cell responses by intervening IL-15 signaling, ameliorating podocyte injury and glomerulosclerosis PMC9372318
GddY mice Spontaneous IgAN Mice model Dietary administration 900 or 1800 ppm (in diet) From 4 weeks old to 12 or 20 weeks old, lasting 8 or 16 weeks Evaluate the efficacy of Sparsentan in the IgAN model, results showed Sparsentan reduced ACR more rapidly and significantly than losartan, and protected glomeruli and podocytes. PMC11361813
Mice COL4A3−/− Mice model Oral gavage 120 mg/kg Once daily, from 3-7 weeks or 5-7 weeks of age Sparsentan significantly delayed onset of glomerulosclerosis, interstitial fibrosis, proteinuria, and glomerular filtration rate decline. Sparsentan attenuated glomerular basement membrane defects, blunted mesangial filopodial invasion into the glomerular capillaries, increased lifespan more than losartan, and lessened changes in profibrotic/proinflammatory genes pathways in both the glomerular and renal cortical compartments. Notably, treatment with sparsentan, but not losartan, prevented accumulation of extracellular matrix in the strial capillary basement membranes in the inner ear and reduced susceptibility to hearing loss. PMC10330771
Mice FSGS model Oral 120 mg/kg Daily for 6 weeks Sparsentan significantly improved glomerular hemodynamics and GFB function, including reduced podocyte calcium levels, increased afferent and efferent arteriole diameters, improved single-nephron glomerular filtration rate and glomerular capillary blood flow, and reduced proteinuria. PMC11466195

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04663204 Immunoglobulin A Nephropathy|K... More >>idney Diseases|Glomerulonephritis, IGA|Glomerulonephritis|Autoimmune Diseases|Immune System Diseases Less << PHASE2 ACTIVE_NOT_RECRUITING 2025-03-31 Cambridge University Hospitals... More >> NHS Trust, Cambridge, England, United Kingdom|Northern Care Alliance NHS Foundation Trust - Salford Royal, Salford, England, United Kingdom|Royal Infirmary of Edinburgh & Western General Hospital, Edinburgh, Scotland, United Kingdom|University Hospital of wales, Cardiff, Wales, CF14 4XW, United Kingdom|Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, LE5 4PW, United Kingdom Less <<
NCT05630612 ANCA Associated Vasculitis|Car... More >>diovascular Diseases|Kidney Diseases Less << PHASE2 ACTIVE_NOT_RECRUITING 2027-09-01 Centre for Cardiovascular Scie... More >>nce, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom Less <<
NCT05856760 Immunoglobulin A Nephropathy PHASE2 COMPLETED 2024-10-25 Travere Investigational Site, ... More >>Birmingham, Alabama, 35233, United States|Travere Investigational Site, Chula Vista, California, 91910, United States|Travere Investigational Site, Garden Grove, California, 92844, United States|Travere Investigational Site, Glendale, California, 91206, United States|Travere Investigational Site, Denver, Colorado, 80230, United States|Travere Investigational Site, Boise, Idaho, 83706, United States|Travere Investigational Site, Chubbuck, Idaho, 83202, United States|Travere Investigational Site, Idaho Falls, Idaho, 83404, United States|Travere Investigational Site, Chicago, Illinois, 60611, United States|Travere Investigational Site, Evergreen Park, Illinois, 60805, United States|Travere Investigational Site, Fort Wayne, Indiana, 46804, United States|Travere Investigational Site, Kansas City, Kansas, 66160, United States|Travere Investigational Site, Louisville, Kentucky, 40205, United States|Travere Investigational Site, Shreveport, Louisiana, 71101, United States|Travere Investigational Site, Albuquerque, New Mexico, 87109, United States|Travere Investigation SIte, Clifton Park, New York, 12065, United States|Travere Investigational Site, Fresh Meadows, New York, 11365, United States|Travere Investigational Site, New York, New York, 10013, United States|Travere Investigational Site, Jacksonville, North Carolina, 28546, United States|Travere Investigational Site, New Bern, North Carolina, 28562, United States|Travere Investigational Site, Columbus, Ohio, 43210, United States|Travere Investigational Site, Philadelphia, Pennsylvania, 19104, United States|Travere Investigational Site, Columbia, South Carolina, 29203, United States|Travere Investigational Site, Dallas, Texas, 75230, United States|Travere Investigational Site, Dallas, Texas, 75246, United States|Travere Investigational Site, Hong Kong, Hong Kong|Travere Investigational Site, Kowloon, Hong Kong|Travere Investigational Site, Shatin, Hong Kong|Travere Investigational Site, Sheung Wan, Hong Kong|Travere Investigational Site, Tsuen Wan, Hong Kong Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.69mL

0.34mL

0.17mL

8.44mL

1.69mL

0.84mL

16.87mL

3.37mL

1.69mL

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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