PPARδ Agonist

1,1'-(Azodicarbonyl)-dipiperidine (ADDP) can be used in the condensation reaction of alcohols with acidic compounds. 1,1'-(Azodicarbonyl)-dipiperidine can also be used in the synthesis of GPR120 agonists with antidiabetic activity, as well as the synthesis of triple agonists for PPARα, PPARγ, and PPARδ. 1,1'-(Azodicarbonyl)-dipiperidine can be used in metabolic disease research.

ZLY06 is an orally active dual agonist of peroxisome proliferator-activated receptor (PPAR) δ and γ (PPAR δ: EC₅₀=341 nM; PPAR γ: EC₅₀=237 nM). ZLY06 induces hepatic lipid accumulation by inhibiting the phosphorylation of AKT1, mediating the upregulation of CD36. In addition, ZLY06 significantly improves glucose and lipid metabolism without increasing body weight, and alleviates fatty liver by promoting β-oxidation of fatty acids and inhibiting hepatic lipogenesis.

PPARα/δ agonist 1 is a potent PPARα/PPARδ dual agonist (PPARα EC₅₀=7.0 nM; PPARδ EC₅₀=8.4 nM). PPARα/δ agonist 1 is a high selectivity over PPARγ (PPARγ EC₅₀=1316.1 nM). PPARα/δ agonist 1 has the potential for the research of nonalcoholic steatohepatitis.

Pparδ agonist 5, an orally active PPARδ-selective agonist (EC₅₀=0.335 μM), is much greater than that of the prototypical standard GW0742. Pparδ agonist 5 promotes improvements in bone density and microarchitecture in vivo.

PPAR agonist 8 is an orally active pan-PPAR agonist, with K_D values of 0.576 μM, 2.06 μM and 1.45 μM for PPARα, PPARγ and PPARδ, respectively. PPAR agonist 8 upregulates the expression of ATP-binding cassette transporter A1 (ABCA1) and promotes cholesterol efflux. PPAR agonist 8 reduces plasma cholesterol levels, decreases cholesterol accumulation in the liver and cholesterol deposition in pancreatic islets, regulates glucose and lipid metabolism, and causes no side effects of weight gain and obesity. PPAR agonist 8 can be used in the research of type 2 diabetes, hepatic steatosis and pancreatic islet dysfunction.

AU403 is a potent, brain-penetrant, isoform-selective LXRβ/PPARδ dual agonist (EC₅₀ ≈ 45 nM for LXRβ and EC₅₀ ≈ 40 nM for PPARδ). AU403 is designed to bypass LXRα-driven hepatotoxicity. AU403 significantly improves cognitive functions and reduces amyloid-β plaque burden in 3xTg-AD mice. AU403 is a promising dual-acting agonist for the research of Alzheimer’s disease.

PPARα/δ agonist 4 is a potent orally active and selective dual peroxisome proliferator-activated receptor (PPAR) α/δ agonist with EC₅₀s of 0.36 and 1.31 nM, respectively. PPARα/δ agonist 4 exhibits >123-fold selectivity over PPARγ (EC₅₀ = 160.84 nM). PPARα/δ agonist 4 upregulates expression of downstream fatty acid oxidation genes PDK4, CPT1A, and ACADVL. PPARα/δ agonist 4 can be used for the research of metabolic dysfunction-associated steatohepatitis.

Seladelpar Lysine dihydrate (MBX-8025 lysine dihydrate) is an orally active, selective PPAR-δ agonist with an EC₅₀ of 2 nM against hPPAR-δ. Seladelpar Lysine dihydrate reduces serum IL-31 and bile acid levels. It alleviates pruritus symptoms. Seladelpar Lysine dihydrate enhances insulin sensitivity, normalizes levels of hyperglycemia, hyperinsulinemia, glucose disposal capacity, serum lipids and hepatic free cholesterol. It reduces steatosis, hepatic inflammation and improves liver fibrosis. Seladelpar Lysine dihydrate reverses the pathological changes of non-alcoholic steatohepatitis (NASH). It is applicable to research related to primary biliary cholangitis and non-alcoholic steatohepatitis (NASH).

PPAR agonist 4 (Compound 12) is an orally active agonist for peroxisome proliferator-activated receptor (PPAR), which activates PPARα, PPARδ and PPARγ with EC₅₀s of 0.7, 0.7 and 1.8 μM, respectively. PPAR agonist 4 exhibits anti-liver fibrosis efficacy.

HSD17B13/PPAR modulator-1 (Compound 17) is a HSD17B13/PPAR multitarget modulator. HSD17B13/PPAR modulator-1 is an inhibitor of HSD17B13, with its IC₅₀ value being 0.91 μM. HSD17B13/PPAR modulator-1 is a PPAR agonist, with the EC₅₀ values for PPARα, PPARδ, and PPARγ being 1.55, 0.12, and 0.01 μM respectively. HSD17B13/PPAR modulator-1 can significantly improve liver function, regulate lipid metabolism, alleviate fibrosis, and exert antioxidant and anti-inflammatory effects in the model of metabolic dysfunction-related steatohepatitis (MASH). HSD17B13/PPAR modulator-1 can be used for the study of MASH.

15-Deoxy-Δ12,14-Prostaglandin J2-2-glyceryl ester is a derivate of 15-Deoxy-Δ-12,14-prostaglandin J2 (HY-108568). 15-Deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) is a cyclopentenone prostaglandin and a metabolite of PGD2. 15-Deoxy-Δ-12,14-prostaglandin J2 is a selective PPARγ (EC₅₀ of 2 µM) and a covalent PPARδ agonist. 15-Deoxy-Δ-12,14-prostaglandin J2 promotes efficient differentiation of C3H10T1/2 fibroblasts to adipocytes with an EC₅₀ of 7 μM.

PPARα agonist 5 is an orally available, selective partial agonist of PPARα (EC₅₀: 3 nM). PPARα agonist 5 reduces lipid accumulation and upregulates key PPARα target genes, exerting anti-fatty liver effects. PPARα agonist 5 also exhibits significant hypolipidemic and hypoglycemic effects through partial PPARγ agonist activity and mild inhibition of protein tyrosine phosphatase 1B (PTP1B) (IC₅₀: 79.1 μM). PPARα agonist 5 has a good safety profile and can be used in the study of type 2 diabetes with dyslipidemia.

PPARδ agonist 10 (compound 7) is an orally active, selective, and partial agonist of PPARδ, with EC₅₀ values of 0.053 μM and 0.30 µM for hPPARδ(LBD)-GAL4 and mPPARδ, respectively. PPARδ agonist 10 is a partial PPARδ agonist in transactivation assay but a full agonist on free fatty acids (FFA) oxidation in muscle cells both in vitro and in vivo. PPARδ agonist 10 can be used for dyslipidemia research.

L-783483 (F3MethylAA) is an agonist for PPARδ. L-783483 ameliorates Carrageenan (HY-125474)-induced paw edema in mice.

PPARα/δ agonist 3 (Compound 8) is the orally active agonist for PPAR, that activates PPARα, PPARδ and PPARγ with EC₅₀s of 5.6, 3.4 and 1278 nM, respectively. PPARα/δ agonist 3 exhibits anticholestatic activity in mouse ANIT- or CDCA (HY-76847)-induced cholestatic liver disease models.

PPARδ agonist 13 is a potent, selective and orally active PPARδ agonist with an EC₅₀ values of 0.50 nM. PPARδ agonist 13 binds to the PPARδ ligand-binding pocket and upregulates PPARδ target gene expression. PPARδ agonist 13 inhibits renal fibroblast activation, restores fatty acid oxidation, and attenuates TGF-β1-induced renal fibroblast activation. PPARδ agonist 13 exhibits anti-renal fibrosis effects in a mouse model of unilateral ureteral obstruction. PPARδ agonist 13 can be used for the research of renal fibrosis.

GW 2433 is a dual PPARα and PPARδ agonist. GW 2433 has the potential for the study of type II diabetes and dyslipidemia.

TZD18 is a potent and orally active PPARα and PPARγ dual agonist with IC₅₀ values of 0.028, 0.057, >10 µM for PPARα, PPARγ, PPARδ, respectively. TZD18 reduces plasma levels of both glucose and triglycerides in diabetic mice. TZD18 has the potential for the research of type 2 diabetes.

NS-220 is an orally active PPARα agonist with high subtype selectivity, with EC₅₀ values of 1.9×10^-8 M, 9.6×10^-6 M and >10^-4 M for PPARα, PPAR γ and PPARδ, respectively. NS-220 is used in the research for hyperlipidemia or metabolic disorders in type-2 diabetes.