Sparsentan
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MedKoo CAT#: 206451

CAS#: 254740-64-2

Description: Sparsentan, also known as RE-021, PS433540 and DARA-a, is a dual angiotensin II and endothelin A receptor antagonist. Sparsentan shows good oral bioavailability in rats, dogs, and monkeys, averaging 40%, 86%, and 21% F, respectively.


Chemical Structure

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Sparsentan
CAS# 254740-64-2

Theoretical Analysis

MedKoo Cat#: 206451
Name: Sparsentan
CAS#: 254740-64-2
Chemical Formula: C32H40N4O5S
Exact Mass: 592.27
Molecular Weight: 592.750
Elemental Analysis: C, 64.84; H, 6.80; N, 9.45; O, 13.50; S, 5.41

Price and Availability

Size Price Availability Quantity
25mg USD 250 2 Weeks
50mg USD 450 2 Weeks
100mg USD 720 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2450 2 Weeks
1g USD 3650 2 Weeks
2g USD 6250 2 Weeks
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Synonym: RE-021; RE021; RE 021; PS-433540; PS 433540; DARA-a; Sparsentan;

IUPAC/Chemical Name: 4'-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)-N-(4,5-dimethylisoxazol-3-yl)-2'-(ethoxymethyl)-[1,1'-biphenyl]-2-sulfonamide

InChi Key: WRFHGDPIDHPWIQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C32H40N4O5S/c1-5-7-14-29-33-32(17-10-11-18-32)31(37)36(29)20-24-15-16-26(25(19-24)21-40-6-2)27-12-8-9-13-28(27)42(38,39)35-30-22(3)23(4)41-34-30/h8-9,12-13,15-16,19H,5-7,10-11,14,17-18,20-21H2,1-4H3,(H,34,35)

SMILES Code: O=S(C1=CC=CC=C1C2=CC=C(CN3C(CCCC)=NC4(CCCC4)C3=O)C=C2COCC)(NC5=NOC(C)=C5C)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: Sparsentan is a dual angiotensin II and endothelin A receptor antagonist with Kis of 0.8 and 9.3 nM, respectively.
In vitro activity: To be determined
In vivo activity: Sparsentan shows promise for treating both kidney and hearing problems in Alport syndrome patients. In an autosomal-recessive Alport mouse model, sparsentan delayed kidney damage onset, reduced protein in urine, and improved kidney function better than losartan. Sparsentan also protected the inner ear from damage, reducing the risk of hearing loss. Even after the onset of kidney damage, sparsentan improved mouse lifespan and kidney health. Reference: J Pathol. 2023 Jul;260(3):353-364. https://pubmed.ncbi.nlm.nih.gov/37256677/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 168.71

Preparing Stock Solutions

The following data is based on the product molecular weight 592.75 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Nagasawa H, Ueda S, Suzuki H, Jenkinson C, Fukao Y, Nakayama M, Otsuka T, Okuma T, Clapper W, Liu K, Nguyen M, Komers R, Suzuki Y. Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy. Nephrol Dial Transplant. 2024 Jan 25:gfae021. doi: 10.1093/ndt/gfae021. Epub ahead of print. PMID: 38271614. 2. Cosgrove D, Gratton MA, Madison J, Vosik D, Samuelson G, Meehan D, Delimont D, Phillips G, Smyth B, Pramparo T, Jarocki D, Nguyen M, Komers R, Jenkinson C. Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice. J Pathol. 2023 Jul;260(3):353-364. doi: 10.1002/path.6087. Epub 2023 May 31. PMID: 37256677; PMCID: PMC10330771.
In vitro protocol: To be determined
In vivo protocol: 1. Nagasawa H, Ueda S, Suzuki H, Jenkinson C, Fukao Y, Nakayama M, Otsuka T, Okuma T, Clapper W, Liu K, Nguyen M, Komers R, Suzuki Y. Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy. Nephrol Dial Transplant. 2024 Jan 25:gfae021. doi: 10.1093/ndt/gfae021. Epub ahead of print. PMID: 38271614. 2. Cosgrove D, Gratton MA, Madison J, Vosik D, Samuelson G, Meehan D, Delimont D, Phillips G, Smyth B, Pramparo T, Jarocki D, Nguyen M, Komers R, Jenkinson C. Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice. J Pathol. 2023 Jul;260(3):353-364. doi: 10.1002/path.6087. Epub 2023 May 31. PMID: 37256677; PMCID: PMC10330771.

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1: Barratt J, Rovin B, Wong MG, Alpers CE, Bieler S, He P, Inrig J, Komers R, Heerspink HJL, Mercer A, Noronha IL, Radhakrishnan J, Rheault MN, Rote W, Trachtman H, Trimarchi H, Perkovic V; PROTECT investigators. IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study. Kidney Int Rep. 2023 Mar 4;8(5):1043-1056. doi: 10.1016/j.ekir.2023.02.1086. PMID: 37180506; PMCID: PMC10166729.


2: Sparsentan. Am J Health Syst Pharm. 2023 May 4:zxad073. doi: 10.1093/ajhp/zxad073. Epub ahead of print. PMID: 37140613.


3: Allison SJ. Interim analysis indicates sparsentan PROTECTs in IgAN. Nat Rev Nephrol. 2023 Apr 20. doi: 10.1038/s41581-023-00719-8. Epub ahead of print. PMID: 37081176.


4: Syed YY. Sparsentan: First Approval. Drugs. 2023 Apr;83(6):563-568. doi: 10.1007/s40265-023-01864-x. PMID: 37022667.


5: Heerspink HJL, Radhakrishnan J, Alpers CE, Barratt J, Bieler S, Diva U, Inrig J, Komers R, Mercer A, Noronha IL, Rheault MN, Rote W, Rovin B, Trachtman H, Trimarchi H, Wong MG, Perkovic V; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double- blind, active-controlled clinical trial. Lancet. 2023 May 13;401(10388):1584-1594. doi: 10.1016/S0140-6736(23)00569-X. Epub 2023 Apr 1. PMID: 37015244.


6: Chen SC, Cai D, Winnett C, Nguyen M, Verma N, Liu K, Preciado P. Effect of Multiple Doses of Sparsentan on the Single-Dose Pharmacokinetics of Dapagliflozin: An Open-Label Drug-Drug Interaction Study in Healthy Adults. Clin Pharmacol Drug Dev. 2023 May;12(5):535-541. doi: 10.1002/cpdd.1231. Epub 2023 Feb 28. PMID: 36852566.


7: Martínez-Díaz I, Martos N, Llorens-Cebrià C, Álvarez FJ, Bedard PW, Vergara A, Jacobs-Cachá C, Soler MJ. Endothelin Receptor Antagonists in Kidney Disease. Int J Mol Sci. 2023 Feb 8;24(4):3427. doi: 10.3390/ijms24043427. PMID: 36834836; PMCID: PMC9965540.


8: Rowe PS, McCarthy EM, Yu AL, Stubbs JR. Correction of Vascular Calcification and Hyperphosphatemia in CKD Rats Treated with ASARM Peptide. Kidney360. 2022 Aug 30;3(10):1683-1698. doi: 10.34067/KID.0002782022. PMID: 36514737; PMCID: PMC9717652.


9: Chavez E, Rodriguez J, Drexler Y, Fornoni A. Novel Therapies for Alport Syndrome. Front Med (Lausanne). 2022 Apr 25;9:848389. doi: 10.3389/fmed.2022.848389. PMID: 35547199; PMCID: PMC9081811.


10: Li L, Tang W, Zhang Y, Jia M, Wang L, Li Q, Han Q, Peng X, Xie Y, Wu J, Wang Z, Zhen J, Wang X, Liu M, Sun Y, Zhang C, Yi F. Targeting tissue-resident memory CD8+ T cells in the kidney is a potential therapeutic strategy to ameliorate podocyte injury and glomerulosclerosis. Mol Ther. 2022 Aug 3;30(8):2746-2759. doi: 10.1016/j.ymthe.2022.04.024. Epub 2022 May 5. PMID: 35514086; PMCID: PMC9372318.


11: Diefenhardt P, Osterholt T, Brinkkötter P. Nephrotisches Syndrom: Überblick und Basis [Nephrotic syndrome: Current understanding and future therapies]. Dtsch Med Wochenschr. 2022 Mar;147(6):332-336. German. doi: 10.1055/a-1334-2135. Epub 2022 Mar 15. PMID: 35291039.


12: Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3. PMID: 35224732; PMCID: PMC8883337.


13: Chuang TH, Cho HY, Wu SN. The Evidence for Sparsentan-Mediated Inhibition of INa and IK(erg): Possibly Unlinked to Its Antagonism of Angiotensin II or Endothelin Type a Receptor. Biomedicines. 2021 Dec 31;10(1):86. doi: 10.3390/biomedicines10010086. PMID: 35052766; PMCID: PMC8773265.


14: Komers R, Diva U, Inrig JK, Loewen A, Trachtman H, Rote WE. Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis. Kidney Int Rep. 2020 Jan 8;5(4):494-502. doi: 10.1016/j.ekir.2019.12.017. PMID: 32274453; PMCID: PMC7136327.


15: Liu ID, Willis NS, Craig JC, Hodson EM. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2019 Nov 21;2019(11):CD003594. doi: 10.1002/14651858.CD003594.pub6. PMID: 31749142; PMCID: PMC6868353.


16: Trachtman H, Nelson P, Adler S, Campbell KN, Chaudhuri A, Derebail VK, Gambaro G, Gesualdo L, Gipson DS, Hogan J, Lieberman K, Marder B, Meyers KE, Mustafa E, Radhakrishnan J, Srivastava T, Stepanians M, Tesar V, Zhdanova O, Komers R; DUET Study Group. DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS. J Am Soc Nephrol. 2018 Nov;29(11):2745-2754. doi: 10.1681/ASN.2018010091. Erratum in: J Am Soc Nephrol. 2019 Mar;30(3):518. PMID: 30361325; PMCID: PMC6218860.


17: Davenport AP, Kuc RE, Southan C, Maguire JJ. New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol Res. 2018 Jun 27;67(Suppl 1):S37-S54. doi: 10.33549/physiolres.933872. PMID: 29947527.


18: Komers R, Gipson DS, Nelson P, Adler S, Srivastava T, Derebail VK, Meyers KE, Pergola P, MacNally ME, Hunt JL, Shih A, Trachtman H. Efficacy and Safety of Sparsentan Compared With Irbesartan in Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET). Kidney Int Rep. 2017 Mar 4;2(4):654-664. doi: 10.1016/j.ekir.2017.02.019. PMID: 29142983; PMCID: PMC5678638.