SPARSENTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C32H40N4O5S
Molecular Weight	592.749
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCC1=NC2(CCCC2)C(=O)N1CC3=CC=C(C(COCC)=C3)C4=C(C=CC=C4)S(=O)(=O)NC5=NOC(C)=C5C

InChI

InChIKey=WRFHGDPIDHPWIQ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C32H40N4O5S
Molecular Weight	592.749
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf|https://adisinsight.springer.com/drugs/800024221 | http://www.retrophin.com/content/pipeline/sparsentan.php | https://www.ncbi.nlm.nih.gov/pubmed/29142983

Sparsentan (RE-021; BMS-346567; PS433540; DARA-a) is a novel candidate in development by Retrophin for the treatment of focal segmental glomerulosclerosis (FSGS), a serious kidney disorder that often leads to end-stage renal disease (ESRD). Sparsentan is a single molecule with antagonism of the endothelin type A receptor (ETAR) and the angiotensin II type 1 receptor (AT1R). Sparsentan has high affinity for both the ETAR (Ki= 12.8 nM) and the AT1R (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors. Endothelin-1 and angiotensin II are thought to contribute to the pathogenesis of IgAN via the ETAR and AT1R, respectively. The US Food and Drug Administration gave accelerated approval on February 17 2023 to sparsentan (Filspari), the first non-immunosuppressive therapy labeled for treating adults with primary immunoglobulin A (IgA) nephropathy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelin receptor ET-A 22 Target ID: CHEMBL252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	Antagonist 2849		12.8 nM [Ki]
Type-1 angiotensin II receptor 41 Target ID: CHEMBL227 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	Antagonist 2849		0.36 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary immunoglobulin A nephropathy 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	Primary		Approved 8583	FILSPARI Approved Use FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g Launch Date 2023

C_max

Value	Dose	Co-administered	Analyte	Population
6.97 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.47 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
83 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
63.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARSENTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
800 mg 1 times / day multiple, oral Highest studied dose\|Studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30361325/	unhealthy, CHILD\|ADULT Health Status: unhealthy Age Group: CHILD\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30361325/	Disc. AE: Adverse event... AEs leading to discontinuation/dose reduction: Adverse event (2.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/30361325/
1600 mg 1 times / day multiple, oral Highest studied dose Dose: 1600 mg, 1 times / day Route: oral Route: multiple Dose: 1600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf#page=13	healthy, UNKNOWN Health Status: healthy Age Group: UNKNOWN Sex: unknown Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf#page=13	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf#page=13

AEs

AE	Significance	Dose	Population
Adverse event	2.7% Disc. AE	800 mg 1 times / day multiple, oral Highest studied dose\|Studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30361325/	unhealthy, CHILD\|ADULT Health Status: unhealthy Age Group: CHILD\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30361325/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inducer 440		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 OATP1B1 1079 P-gp 1741 OAT2 153 BCRP 910 OCT2 779 MATE1 415 CYP3A 227 MRP 9 MATE2K 17 NTCP 39 OAT1 725 OAT3 747	CYP3A 220 OATP1B1 503 P-gp 2052 OATP1B3 435 BCRP 697	CYP2C19 329 CYP2B6 669 CYP3A 142

Drug as perpetrator

Drug as victim

Target	Modality	Activity	Clinical evidence
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 16.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 16.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 16.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 16.0	yes
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 10 \| 16	yes	yes (co-administration study) Comment: Itraconazole increased Cmax by 25% and AUC by 174% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 10 \| 16

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf Page: 14.0

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to the recommended dose of 400 mg once daily, as tolerated. When resuming treatment with FILSPARI after an interruption, consider titration of FILSPARI, starting at 200 mg once daily. After 14 days, increase to the recommended dose of 400 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Sparsentan is a highly potent dual angiotensin II and endothelin A receptor antagonist with Kis of 0.8 and 9.3 nM, respectively.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:32:16 GMT 2025` Edited by `admin` on `Mon Mar 31 21:32:16 GMT 2025`
Record UNII	9242RO5URM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

sparsentan [INN]

Preferred Name

English

SPARSENTAN

Official Name

English

DARA

Common Name

English

RE-021

Code

English

FILSPARI

Brand Name

English

Sparsentan [WHO-DD]

Common Name

English

(1,1'-BIPHENYL)-2-SULFONAMIDE, 4'-((2-BUTYL-4-OXO-1,3-DIAZASPIRO(4.4)NON-1-EN-3-YL)METHYL)-N-(4,5-DIMETHYL-3-ISOXAZOLYL)-2'-(ETHOXYMETHYL)-

Systematic Name

English

PS-433540

Code

English

SPARSENTAN [USAN]

Common Name

English

4'-((2-BUTYL-4-OXO-1,3-DIAZASPIRO(4.4)NON-1-EN-3-YL)METHYI)-N-(4,5- DIMETHYLISOXAZOL-3-YL)-2'-(ETHOXYMETHYL)BIPHENYL-2-SULFONAMIDE

Systematic Name

English

PS433540

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C66930