PPARγ Inhibitor

Oleuropein, found in olive leaves and oil, exerts antioxidant, anti-inflammatory and anti-atherogenic effects through direct inhibition of PPARγ transcriptional activity. Oleuropein induces apoptosis in breast cancer cells via the p53-dependent pathway and through the regulation of Bax and Bcl2 genes. Oleuropein also inhibits aromatase.

Fucoxanthin (all-trans-Fucoxanthin) is a marine carotenoid and shows anti-obesity, anti-diabetic, anti-oxidant, anti-inflammatory and anticancer activities.

Ginsenoside Rh1 (Prosapogenin A2) inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β.

Agrimol B, a polyphenol, is an orally active and potent SIRT1 activator. Agrimol B shows anti-adipogenic and anticancer activity. Agrimol B shows antibacterial activity against plant pathogens. Agrimol B dramatically inhibits 3T3-L1 adipocyte differentiation by reducing PPARγ, C/EBPα, FAS, UCP-1, and apoE expression. The action of Agrimol B on the cancer cells is likely derived from its effect on c-MYC, SKP2 and p27.

FX-909 is a covalent peroxisome proliferator-activated receptor gamma (PPARG) inverse agonist. FX-909 can be used for the research of cancer.

Sinigrin (Allyl-glucosinolate) is an orally active glucosinolate found in cruciferous plants. Sinigrin possesses multiple activities such as anti-cancer, antibacterial, antifungal, anti-inflammatory, antioxidant, and inhibition of fat synthesis. Sinigrin can be used in the research of tumors, inflammatory, and metabolic diseases.

Urolithin D (3,4,8,9-Tetrahydroxy urolithin) is a colonic metabolite of Ellagitannins and a competitive, reversible, and selective antagonist of the EphA receptor. Urolithin D inhibits EphA2-ephrin-A1 binding with an IC₅₀ of 0.9 μM. Urolithin D is also a potent antioxidant that scavenges free radicals and repairs oxidized DNA damage. Additionally, Urolithin D suppresses triglyceride accumulation and promotes fatty acid oxidation by activating the AMPK signaling pathway. Urolithin D can be used for research on tumors, metabolic, and inflammatory diseases.

Avicularin is an orally active flavonoid. Avicularin inhibits NF-κB (p65), COX-2 and PPAR-γ activities. Avicularin has anti-inflammatory, anti-infectious anti-allergic, anti-oxidant, hepatoprotective, and anti-tumor activities.

SR1664 is a PPARγ antagonist. SR1664 binds to PPARγ and potently inhibits Cdk5-mediated PPARγ phosphorylation (IC₅₀=80 nM; K_i= 28.67 nM).

Rubrofusarin gentiobioside (Rrubrofusarin-6-β-gentiobioside) is an orally active weak inhibitor of PTP1B and MAO-A (IC₅₀ >100 μM), and its glycosylation modification results in lower biological activity than its aglycone Rubrofusarin (HY-130307). Rubrofusarin gentiobioside promotes AMPK phosphorylation in an LKB1-independent manner and inhibits the mTOR signaling pathway, thereby downregulating the expressions of PPARγ, C/EBPα, as well as FAS, LPL and aP2. Rubrofusarin gentiobioside inhibits lipid accumulation, reduces body weight and epididymal white adipose tissue volume, improves fatty liver, and shows no cytotoxicity to hepatocytes. Rubrofusarin gentiobioside is widely used in obesity-related studies.

Norathyriol (Mangiferitin) is a natural metabolite of Mangifera. Norathyriol inhibits α-glucosidase in a noncompetitive manner with an IC₅₀ of 3.12 μM. Norathyriol inhibits PPARα, PPARβ, and PPARγ with IC₅₀s of 92.8 µM, 102.4 µM, and 153.5 µM, respectively. Antioxidant, anticancer, antimicrobial, anti-inflammatory, anti-bacterial activities.

PPARγ-IN-2 (Compound 5a) is a PPARγ inhibitor. PPARγ-IN-2 inhibits TG accumulation in 3T3-L1 preadipocytes (EC₅₀: 0.106 μM). PPARγ-IN-2 inhibits high-cholesterol diet (HFC)-induced obesity and related metabolic syndrome, and reduces lipid accumulation in adipose tissue.

FTX-6746 is an orally active PPARG inhibitor. FTX-6746 shows potent tumor inhibition in mouse xenograft models.

GSK1820795A, as a telmisartan analog, is a selective hGPR132a antagonist. GSK1820795A blocks activation of yeast cells expressing hGPR132a by N-acylamides. GSK1820795A is also a angiotensin II antagonists and partial PPARγ agonists (compound 38).

Mifobate (SR-202) is a potent and specific PPARγ antagonist. Mifobate (SR-202) selectively inhibits Thiazolidinedione (TZD)-induced PPARγ transcriptional activity (IC₅₀=140 μM). Mifobate (SR-202) does not affect basal or ligand-stimulated transcriptional activity of PPARα, PPARβ, or the farnesoid X receptor (FXR). Mifobate (SR-202) shows antiobesity and antidiabetic effects.

6-Thioinosine (6TI) is a purine antimetabolite and an anti-adipogenic agent. 6-Thioinosine reduces the mRNA levels of PPARγ and C/EBPα and downregulates the mRNA levels of PPARγ target genes (LPL, CD36, aP2, and LXRα). 6-Thioinosine exerts its anti-adipogenic effects by downregulating PPARγ through JNK-dependent iNOS upregulation. 6-Thioinosine can be used to study adipocyte dysfunction.

Alisol A 24-acetate (Alisol A monoacetate) is an orally active derivative of protostane-type tetracyclic triterpenoid. Alisol A 24-acetate upregulates the expression of adiponectin, AMPKα, CPT1, and ACOX1; downregulates the expression of SREBP-1c, ACC, FAS, Bcl-2, Bcl-xl, PPAR-γ, perilipin A, and NFATc1; inhibits the activity of PI3K/Akt/mTOR and HMGR; and activates the PKA and ERK signaling pathways. Alisol A 24-acetate regulates cell apoptosis (apoptosis), autophagy (Autophagy, hepatic lipid accumulation, inflammatory response, neuroprotection, MRSA membrane integrity, and osteoclast differentiation. Alisol A 24-acetate can be used in research related to non-alcoholic fatty liver disease, nephrotoxicity, obesity, global cerebral ischemia-reperfusion injury, bacterial infection, and osteoporosis.

Vitisin A ((+)-Vitisin A) is an orally active natural product with multiple pharmacological activities including anti-inflammatory, anti-tumor, anti-oxidant, anti-pathogenic microorganism, hypoglycemic and lipid-regulating, anti-osteoporotic, neuroprotective and cardiovascular protective effects. Vitisin A exhibits inhibitory effects on human AChE and MAO-B with IC₅₀ values of 1.29 µM and 4.94 µM, respectively. Vitisin A inhibits the ERK, MAPK, NF-κB, STAT1, HMGCR and TRAF6 pathways, downregulates the related phosphorylation and protein expression, while activates the Nrf2/HO-1 pathway and upregulates p21 expression. Vitisin A induces tumor cell apoptosis and cell cycle arrest, inhibits adipogenesis and lipid accumulation, while alleviates oxidative stress, suppresses inflammatory responses, blocks hepatic fibrosis, Cuproptosis and cholesterol synthesis, and increases the expression levels of central BDNF and TrkB. Vitisin A can be used in the research of tumors, infectious diseases, metabolic diseases, bone and joint diseases, liver diseases, skin injuries, as well as neurodegenerative and cognitive dysfunction-related diseases.

PPARγ phosphorylation inhibitor 1 (Compound 10) is a potent PPARγ binder with the IC₅₀ of 24 nM. PPARγ phosphorylation inhibitor 1 inhibits CDK5-mediated phosphorylation of PPARγ Ser273 with the IC₅₀ of 160 nM. PPARγ phosphorylation inhibitor 1 displays negligible PPARγ agonism in a reporter gene assay. Antidiabetic effects.

Saringosterol is an orally active steroid found in Sargassum muticum. Saringosterol is a LXR agonist. Saringosterol can lower cholesterol levels and inhibit the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα). Saringosterol has anti-obesity, anti-atherosclerosis, anti-Mycobacterium tuberculosis and anti-depressant activities.