Sparsentan | CAS#254740-64-2 | DARA antagonist

MedKoo Cat#: 206451 | Name: Sparsentan

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Sparsentan, also known as RE-021, PS433540 and DARA-a, is a dual angiotensin II and endothelin A receptor antagonist. Sparsentan has demonstrated potent antagonism of ETA and AT1 receptors with Ki values in the low nanomolar range (ETA: ~0.8 nM; AT1: ~9 nM), resulting in effective blockade of vasoconstrictive and pro-fibrotic signaling pathways. This dual mechanism leads to reductions in proteinuria and stabilization of renal function, as evidenced in the DUET and PROTECT trials. Pharmacodynamically, sparsentan reduces blood pressure and proteinuria more effectively than angiotensin receptor blockers alone, supporting its superior therapeutic potential in progressive glomerular diseases.

Chemical Structure

Sparsentan

CAS#254740-64-2

Theoretical Analysis

MedKoo Cat#: 206451

Name: Sparsentan

CAS#: 254740-64-2

Chemical Formula: C32H40N4O5S

Exact Mass: 592.2719

Molecular Weight: 592.75

Elemental Analysis: C, 64.84; H, 6.80; N, 9.45; O, 13.50; S, 5.41

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 720.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,450.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 6,250.00	2 Weeks

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Related CAS #

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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

Product Data

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	100.0	168.71

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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: 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. 2: 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. 3: 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. doi: 10.1681/ASN.2019010051. PMID: 30361325; PMCID: PMC6218860. 4: 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. 5: 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. 6: 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. 7: 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. 8: 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. 9: 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. 10: 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. 11: 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. 12: 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. 13: 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. 14: 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. 15: Syed YY. Sparsentan: First Approval. Drugs. 2023 Apr;83(6):563-568. doi: 10.1007/s40265-023-01864-x. Erratum in: Drugs. 2023 Jul;83(10):955. doi: 10.1007/s40265-023-01900-w. PMID: 37022667; PMCID: PMC10232600. 16: Allison SJ. Interim analysis indicates sparsentan PROTECTs in IgAN. Nat Rev Nephrol. 2023 Jun;19(6):359. doi: 10.1038/s41581-023-00719-8. PMID: 37081176. 17: Sparsentan. Am J Health Syst Pharm. 2023 Jun 22;80(13):792-795. doi: 10.1093/ajhp/zxad073. PMID: 37140613. 18: 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. 19: Wada R, Kleijn HJ, Zhang L, Chen SC. Population pharmacokinetic analysis of sparsentan in healthy volunteers and patients with focal segmental glomerulosclerosis. CPT Pharmacometrics Syst Pharmacol. 2023 Aug;12(8):1080-1092. doi: 10.1002/psp4.12996. Epub 2023 Jun 1. PMID: 37221817; PMCID: PMC10431048. 20: 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.