Seladelpar sodium | CAS#851528-79-5 | PPARδ receptor agonist

MedKoo Cat#: 522548 | Name: Seladelpar sodium

Description:

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

Seladelpar, also known as MBX-8025 and RWJ-800025, is a selective peroxisome proliferator-activated receptor (SPPAR) -δ receptor agonist. MBX-8025 may have potential use for the treatment of dyslipidemia, metabolic syndrome, type 2 diabetes, and non-alcoholic steatohepatitis.

Chemical Structure

Seladelpar sodium

CAS#Seladelpar sodium

Theoretical Analysis

MedKoo Cat#: 522548

Name: Seladelpar sodium

CAS#: Seladelpar sodium

Chemical Formula: C21H22F3NaO5S

Exact Mass: 0.0000

Molecular Weight: 466.45

Elemental Analysis: C, 54.07; H, 4.75; F, 12.22; Na, 4.93; O, 17.15; S, 6.87

Price and Availability

Related CAS #

851528-79-5 (free acid) 928821-40-3 (lysine hydrate) 928821-41-4 (lysine) Seladelpar sodium

Synonym

Seladelpar sodium; Seladelpar; MBX-8025; MBX 8025; MBX8025; RWJ-800025; RWJ 800025; RWJ800025;

IUPAC/Chemical Name

sodium (R)-2-(4-((2-ethoxy-3-(4-(trifluoromethyl)phenoxy)propyl)thio)-2-methylphenoxy)acetate

InChi Key

XCAXFCPCOXDEHC-UNTBIKODSA-M

InChi Code

InChI=1S/C21H23F3O5S.Na/c1-3-27-17(11-28-16-6-4-15(5-7-16)21(22,23)24)13-30-18-8-9-19(14(2)10-18)29-12-20(25)26;/h4-10,17H,3,11-13H2,1-2H3,(H,25,26);/q;+1/p-1/t17-;/m1./s1

SMILES Code

O=C([O-])COC1=CC=C(SC[C@H](OCC)COC2=CC=C(C(F)(F)F)C=C2)C=C1C.[Na+]

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

Seladelpar (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code names MBX-8025, RWJ-800025) is a PPARδ receptor agonist that is being investigated for drug use by Metabolex. According to a press release they are examining its potential use for the treatment of dyslipidemia, metabolic syndrome, type 2 diabetes, and non-alcoholic steatohepatitis (NASH). The compound was licensed from Janssen Pharmaceutica NV. The drug completed a phase II trial for primary biliary cholangitis. "Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus." A phase III trial in patients with PBC also found reduced pruritus and improved liver biochemistry, despite being terminated early. from https://en.wikipedia.org/wiki/Seladelpar

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Seladelpar is a potent and specific PPAR-δ agonist (EC50 = 2 nM).

In vitro activity:

To be determined

In vivo activity:

In a mouse model of non-alcoholic steatohepatitis (NASH), seladelpar substantially improved NASH and NASH-induced fibrosis outcomes, alone and in combination with liraglutide. Seladelpar treatment markedly improved plasma markers of liver function and there were also robust reductions in liver steatosis. Seladelpar produced a reorganization of metabolic gene expression, particularly for genes promoting peroxisomal and mitochondrial lipid oxidation. Reference: Am J Physiol Gastrointest Liver Physiol. 2023 Nov 28. https://pubmed.ncbi.nlm.nih.gov/38014444/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	224.99

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 466.45 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. Choi YJ, Johnson JD, Lee JJ, Song J, Matthews M, Hellerstein MK, McWherter CA. Seladelpar combined with complementary therapies improves fibrosis, inflammation and liver injury in a mouse model of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2023 Nov 28. doi: 10.1152/ajpgi.00158.2023. Epub ahead of print. PMID: 38014444. 2. Wetten A, Jones DEJ, Dyson JK. Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). Expert Opin Investig Drugs. 2022 Oct;31(10):1101-1107. doi: 10.1080/13543784.2022.2130750. Epub 2022 Oct 8. PMID: 36194037.

In vitro protocol:

To be determined

In vivo protocol:

1: Vuppalanchi R, Kowdley KV. Editorial: The evolving paradigms and treatments for primary biliary cholangitis. Aliment Pharmacol Ther. 2024 Jan;59(2):280-281. doi: 10.1111/apt.17779. PMID: 38153286. 2: Kremer AE, Mayo MJ, Hirschfield GM, Levy C, Bowlus CL, Jones DE, Johnson JD, McWherter CA, Choi YJ. Seladelpar treatment reduces interleukin-31 and pruritus in patients with primary biliary cholangitis. Hepatology. 2023 Dec 20. doi: 10.1097/HEP.0000000000000728. Epub ahead of print. PMID: 38117036. 3: Choi YJ, Johnson JD, Lee JJ, Song J, Matthews M, Hellerstein MK, McWherter CA. Seladelpar combined with complementary therapies improves fibrosis, inflammation and liver injury in a mouse model of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2023 Nov 28. doi: 10.1152/ajpgi.00158.2023. Epub ahead of print. PMID: 38014444. 4: Mayo MJ, Vierling JM, Bowlus CL, Levy C, Hirschfield GM, Neff GW, Galambos MR, Gordon SC, Borg BB, Harrison SA, Thuluvath PJ, Goel A, Shiffman ML, Swain MG, Jones DEJ, Trivedi P, Kremer AE, Aspinall RJ, Sheridan DA, Dörffel Y, Yang K, Choi YJ, McWherter CA. Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Aliment Pharmacol Ther. 2024 Jan;59(2):186-200. doi: 10.1111/apt.17755. Epub 2023 Oct 30. PMID: 37904314. 5: Palmer M, Kleiner DE, Goodman Z, Brunt E, Avigan MI, Regev A, Hayashi PH, Lewis JH, Mehta R, Harrison SA, Siciliano M, McWherter CA, Vuppalanchi R, Behling C, Miller V, Chalasani N, Sanyal AJ. Liver biopsy for assessment of suspected drug-induced liver injury in metabolic dysfunction-associated steatohepatitis clinical trials: Expert consensus from the Liver Forum. Aliment Pharmacol Ther. 2024 Jan;59(2):201-216. doi: 10.1111/apt.17762. Epub 2023 Oct 25. PMID: 37877759. 6: Kamata S, Honda A, Ishikawa R, Akahane M, Fujita A, Kaneko C, Miyawaki S, Habu Y, Shiiyama Y, Uchii K, Machida Y, Oyama T, Ishii I. Functional and Structural Insights into the Human PPARα/δ/γ Targeting Preferences of Anti-NASH Investigational Drugs, Lanifibranor, Seladelpar, and Elafibranor. Antioxidants (Basel). 2023 Jul 29;12(8):1523. doi: 10.3390/antiox12081523. PMID: 37627519; PMCID: PMC10451623. 7: Hirschfield GM, Shiffman ML, Gulamhusein A, Kowdley KV, Vierling JM, Levy C, Kremer AE, Zigmond E, Andreone P, Gordon SC, Bowlus CL, Lawitz EJ, Aspinall RJ, Pratt DS, Raikhelson K, Gonzalez-Huezo MS, Heneghan MA, Jeong SH, Ladrón de Guevara AL, Mayo MJ, Dalekos GN, Drenth JPH, Janczewska E, Leggett BA, Nevens F, Vargas V, Zuckerman E, Corpechot C, Fassio E, Hinrichsen H, Invernizzi P, Trivedi PJ, Forman L, Jones DEJ, Ryder SD, Swain MG, Steinberg A, Boudes PF, Choi YJ, McWherter CA; ENHANCE Study Group*. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology. 2023 Aug 1;78(2):397-415. doi: 10.1097/HEP.0000000000000395. Epub 2023 Apr 6. PMID: 37386786; PMCID: PMC10344437. 8: Levy C, Manns M, Hirschfield G. New Treatment Paradigms in Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2023 Jul;21(8):2076-2087. doi: 10.1016/j.cgh.2023.02.005. Epub 2023 Feb 19. PMID: 36809835. 9: Colapietro F, Gershwin ME, Lleo A. PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales. J Transl Autoimmun. 2023 Jan 5;6:100188. doi: 10.1016/j.jtauto.2023.100188. PMID: 36684809; PMCID: PMC9850184. 10: Xu C, Yue R, Lv X, Wang S, Du M. Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis. Front Pharmacol. 2022 Oct 20;13:835991. doi: 10.3389/fphar.2022.835991. PMID: 36339545; PMCID: PMC9631940. 11: Wetten A, Jones DEJ, Dyson JK. Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). Expert Opin Investig Drugs. 2022 Oct;31(10):1101-1107. doi: 10.1080/13543784.2022.2130750. Epub 2022 Oct 8. PMID: 36194037. 12: Bowlus CL, Levy C, Hirschfield GM. Reply to: "Seladelpar in patients with primary biliary cholangitis: Need for a closer look!". J Hepatol. 2022 Nov;77(5):1452-1453. doi: 10.1016/j.jhep.2022.07.024. Epub 2022 Aug 14. PMID: 35977610. 13: Vijayakumar A, Okesli-Armlovich A, Wang T, Olson I, Seung M, Kusam S, Hollenback D, Mahadevan S, Marchand B, Toteva M, Breckenridge DG, Trevaskis JL, Bates J. Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis. Hepatol Commun. 2022 Sep;6(9):2298-2309. doi: 10.1002/hep4.2011. Epub 2022 Jun 23. PMID: 35735253; PMCID: PMC9426400. 14: Kouno T, Liu X, Zhao H, Kisseleva T, Cable EE, Schnabl B. Selective PPARδ agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 via the fibroblast growth factor 21 signaling pathway. J Biol Chem. 2022 Jul;298(7):102056. doi: 10.1016/j.jbc.2022.102056. Epub 2022 May 20. PMID: 35605662; PMCID: PMC9214809. 15: Mishra AK, Singh SP. Seladelpar in patients with primary biliary cholangitis: Need for a closer look! J Hepatol. 2022 Nov;77(5):1451. doi: 10.1016/j.jhep.2022.04.039. Epub 2022 May 17. PMID: 35594993. 16: Dhingra S, Mahadik JD, Tarabishy Y, May SB, Vierling JM. Prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and biliary injury in liver biopsies from patients with non-alcoholic steatohepatitis. Pathology. 2022 Oct;54(6):686-693. doi: 10.1016/j.pathol.2022.01.009. Epub 2022 May 5. PMID: 35525796. 17: Bowlus CL, Galambos MR, Aspinall RJ, Hirschfield GM, Jones DEJ, Dörffel Y, Gordon SC, Harrison SA, Kremer AE, Mayo MJ, Thuluvath PJ, Levy C, Swain MG, Neff GW, Sheridan DA, Stanca CM, Berg CP, Goel A, Shiffman ML, Vierling JM, Boudes P, Steinberg A, Choi YJ, McWherter CA. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. J Hepatol. 2022 Aug;77(2):353-364. doi: 10.1016/j.jhep.2022.02.033. Epub 2022 Mar 30. PMID: 35367282. 18: Kremer AE, Mayo MJ, Hirschfield G, Levy C, Bowlus CL, Jones DE, Steinberg A, McWherter CA, Choi YJ. Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis. Liver Int. 2022 Jan;42(1):112-123. doi: 10.1111/liv.15039. Epub 2021 Aug 26. PMID: 34403559. 19: ENHANCE: Safety and Efficacy of Seladelpar in Patients With Primary Biliary Cholangitis-A Phase 3, International, Randomized, Placebo-Controlled Study. Gastroenterol Hepatol (N Y). 2021 Feb;17(2 Suppl 3):5-6. PMID: 34135711; PMCID: PMC8191827. 20: Xiang, X., Han, S., Xu, D., Chen, Q., Ji, R., Zhao, Z., ... & Ai, Q. (2023). Oleic and palmitic acids induce hepatic angiopoietin-like 4 expression predominantly via PPAR-γ in Larimichthys crocea. British Journal of Nutrition, 129(10), 1657-1666.