Saroglitazar

• CAT Number: I003736
• CAS Number: 495399-09-2
• Molecular Formula: C25H29NO4S
• Molecular Weight: 439.57
• Purity: ≥95%
• Target: PPAR
• Solubility: DMSO
• Storage: Store at -20°C
• IC50: 0.65 pM (hPPARα, in HepG2 cells), 3 nM (hPPARγ, in HepG2 cells)
• IUPAC Name: (2S)-2-ethoxy-3-[4-[2-[2-methyl-5-(4-methylsulfanylphenyl)pyrrol-1-yl]ethoxy]phenyl]propanoic acid
• InChI: InChI=1S/C25H29NO4S/c1-4-29-24(25(27)28)17-19-6-10-21(11-7-19)30-16-15-26-18(2)5-14-23(26)20-8-12-22(31-3)13-9-20/h5-14,24H,4,15-17H2,1-3H3,(H,27,28)/t24-/m0/s1
• InChIKey: MRWFZSLZNUJVQW-DEOSSOPVSA-N
• SMILES: O=C(O)[C@@H](OCC)CC1=CC=C(OCCN2C(C)=CC=C2C3=CC=C(SC)C=C3)C=C1

Saroglitazar (CAT: I003736) is a novel peroxisome proliferator-activated receptor (PPAR) agonist that exhibits predominant activity towards PPARα and moderate activity towards PPARγ. It has been shown to effectively reduce triglycerides (TG), LDL cholesterol, VLDL cholesterol, and non-HDL cholesterol while increasing HDL cholesterol levels, which are characteristic features of atherogenic diabetic dyslipidemia (ADD). Saroglitazar acts as a dual PPAR agonist, targeting both the α (alpha) and γ (gamma) subtypes of PPAR. Activating PPARα, it helps lower elevated triglyceride levels, while its action on PPARγ improves insulin resistance and contributes to lower blood sugar levels. Saroglitazar is a novel, first-in-class drug that holds promise in the treatment of dyslipidemia and diabetes.

Overview of Clinical Research

Originator: Zydus-Cadila
Developer: Zydus Cadila
Class: Antihyperglycaemics; Antihyperlipidaemics; Small molecules
Mechanism of Action: Peroxisome proliferator-activated receptor alpha agonists; Peroxisome proliferator-activated receptor gamma agonists
Orphan Drug Status: No

Reference

1. Diabetes Metab Syndr Obes. 2015 Apr 15;8:189-96. doi: 10.2147/DMSO.S49592. eCollection 2015.
Saroglitazar for the treatment of hypertrig-lyceridemia in patients with type 2 diabetes: current evidence.
Sosale A(1), Saboo B(2), Sosale B(1).
Author information:
(1)Diacon Hospital, Bangalore, India. (2)Dia Care (Diabetes Care and Hormone Clinic), Ahmedabad, India.
Diabetes mellitus (DM) is one of the most dreaded metabolic disorders in the world today. It is the leading cause of morbidity and mortality, and plays a cardinal role in quality of life and health economics. DM is associated with a high prevalence of microvascular and macrovascular complications. DM is a very important cardiovascular (CV) risk factor. Cardiovascular disease (CVD) has been implicated as the prime cause of mortality and morbidity in patients with DM. Hence, treatment of DM goes beyond glycemic control, and demands a multidisciplinary approach that comprehensively targets risk factors inherent in CV events. Lipid abnormalities are undoubtedly common in patients with DM, and they contribute to an increased risk of CVD. A high-risk lipid profile, termed atherogenic dyslipidemia of diabetes (ADD), is known to occur in patients with DM. The use of lipid-lowering agents, a quintessential part of the multifactorial risk factor approach, is a crucial intervention to minimize diabetes-related complications. In this article, we discuss the role of peroxisome proliferator activator receptor (PPAR) alpha/gamma (α/γ) agonist, saroglitazar, in the management of ADD. While statins are irrefutably the first line of drugs for dyslipidemia management in patients with residual CV risk while on a statin, PPAR α/γ agonists have been found to be of substantial benefit. Data from the PRESS I-VI clinical trials testify to the fact that saroglitazar and fibrates have similar efficacy in reducing triglycerides and improving high-density lipoprotein. The ancillary benefit of improved glycemic control, without the weight gain of PPAR γ agonists, is an added advantage. Reduction in ADD, improved glycemic control, efficacy at par with fibrates, and an acceptable safety profile form the grounds on which this group of PPAR α/γ agonists, with their novel mechanism, holds a promising future in the management of diabetic dyslipidemia.
2. Expert Opin Pharmacother. 2015 Mar;16(4):597-606. doi: 10.1517/14656566.2015.1009894.
Saroglitazar for the treatment of dyslipidemia in diabetic patients.
Joshi SR(1).
Author information:
(1)Lilavati Hospital and Research Centre – Endocrinology , A – 791 Bandra Reclamation Bandra (W), Mumbai, Maharashtra 400050 , India .
INTRODUCTION: Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. AREAS COVERED: This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. EXPERT OPINION: Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.