Abstract:
:Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate existing clinical evidence of PPAR modulators, highlighting their clinical prospects and challenges. Findings from clinical trials revealed that different agonists of the same PPAR subtype could present different safety profiles and clinical outcomes in a disease-dependent manner. Pemafibrate, due to its high selectivity, is likely to replace other PPARα agonists for dyslipidemia and cardiovascular diseases. PPARγ agonist pioglitazone showed tremendous promises in many non-metabolic disorders like chronic kidney disease, depression, inflammation, and autoimmune diseases. The clinical niche of PPARβ/δ agonists is less well-explored. Interestingly, dual- or pan-PPAR agonists, namely chiglitazar, saroglitazar, elafibranor, and lanifibranor, are gaining momentum with their optimistic outcomes in many diseases including type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and primary biliary cholangitis. Notably, the preclinical and clinical development for PPAR antagonists remains unacceptably deficient. We anticipate the future design of better PPAR modulators with minimal off-target effects, high selectivity, superior bioavailability, and pharmacokinetics. This will open new possibilities for PPAR ligands in medicine.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Cheng HS,Tan WR,Low ZS,Marvalim C,Lee JYH,Tan NSdoi
10.3390/ijms20205055subject
Has Abstractpub_date
2019-10-11 00:00:00issue
20issn
1422-0067pii
ijms20205055journal_volume
20pub_type
杂志文章,评审abstract::Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O-methylflavonols and O-methylcyanidins that possess an aryl group at the 8-position. We synthesized per-O-methylquercetin from que...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18020427
更新日期:2017-02-16 00:00:00
abstract::Two new ergostane-type sterols; (22E)-5α,6α-epoxyergosta-8,14,22-triene-3β,7β-diol (1) and 5α,6α-epoxyergost-8(14)-ene-3β,7α-diol (2) were isolated from the fruiting bodies of king trumpet mushroom (Pleurotus eryngii), along with eight known compounds (3-10). All isolated compounds were evaluated for their inhibitory ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18112479
更新日期:2017-11-21 00:00:00
abstract::Mucin1 (MUC1) is aberrantly glycosylated and overexpressed in various cancers, and it plays a crucial role in cancerogenesis. MUC1 is a type I membranous protein composed of α and β subunits. MUC1-α can be cleaved in cancers, exposing MUC1-β (MUC1-C). MUC1-C is involved with multiple cancer cellular functions, which m...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21093258
更新日期:2020-05-05 00:00:00
abstract::Acidovorax citrulli (A. citrulli) strains cause bacterial fruit blotch (BFB) in cucurbit crops and affect melon significantly. Numerous strains of the bacterium have been isolated from melon hosts globally. Strains that are aggressively virulent towards melon and diagnostic markers for detecting such strains are yet t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20112715
更新日期:2019-06-02 00:00:00
abstract::: The highly conserved transcription factor Pax6 is involved in the development of the eyes, brain, and pancreas in vertebrates and invertebrates, whereas the additional expression pattern in other organs is still elusive. In this study, we cloned and characterized two pax6 homologs in blunt snout bream (Megalobrama a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20071710
更新日期:2019-04-05 00:00:00
abstract::Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen frequently associated with acute diarrhea in children and travelers to endemic regions. EAEC was found the most prevalent bacterial diarrheal pathogen from hospitalized Bolivian children less than five years of age with acute diarrhea from 2007 to 2010....
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21249543
更新日期:2020-12-15 00:00:00
abstract::Recent studies have shown that plumbagin has anti-inflammatory, anti-allergic, antibacterial, and anti-cancer activities; however, it has not yet been shown whether plumbagin suppresses alpha-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis to prevent hyperpigmentation. In this study, we demonstrated t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18020320
更新日期:2017-02-03 00:00:00
abstract::Rolling-circle replication (RCR) elements constitute a diverse group that includes viruses, plasmids, and transposons, present in hosts from all domains of life. Eukaryotic RCR transposons, also known as Helitrons, are found in species from all eukaryotic kingdoms, sometimes representing a large portion of their genom...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19103079
更新日期:2018-10-09 00:00:00
abstract::Distal-less homeobox 5 (Dlx5) is a negative regulator of adipogenesis. Dlx5 expression is decreased by adipogenic stimuli, but the mechanisms of Dlx5 downregulation by adipogenic stimuli have not yet been determined. Here, we tested the impact of cAMP/PKA (protein kinase A) signaling induced by 3-isobutyl-1 methyl xan...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19103161
更新日期:2018-10-14 00:00:00
abstract::Soluble receptors are widely understood to be freestanding moieties formed via cleavage from their membrane-bound counterparts. They have unique structures, are found among various receptor families, and have intriguing mechanisms of generation and release. Soluble receptors' ability to exhibit pleiotropic action by r...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms22031108
更新日期:2021-01-23 00:00:00
abstract::Effect of H2O and NH3 on the synergistic oxidation reaction of SO2 and NO2 is investigated by theoretical calculation using the molecule system SO2-2NO2-nH2O (n = 0, 1, 2, 3) and SO2-2NO2-nH2O-mNH3 (n = 0, 1, 2; m = 1, 2). Calculated results show that SO2 is oxidized to SO3 by N2O4 intermediate. The additional H2O in ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20153746
更新日期:2019-07-31 00:00:00
abstract::We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19092743
更新日期:2018-09-13 00:00:00
abstract::Chitooligosaccharide (COS), which is acknowledged for possessing multiple functions, is a kind of low-molecular-weight polymer prepared by degrading chitosan via enzymatic, chemical methods, etc. COS has comprehensive applications in various fields including food, agriculture, pharmacy, clinical therapy, and environme...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19082197
更新日期:2018-07-27 00:00:00
abstract::The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20061484
更新日期:2019-03-25 00:00:00
abstract::Glycosyltransferases that use polyisoprenol-linked donor substrates are categorized in the GT-C superfamily. In eukaryotes, they act in the endoplasmic reticulum (ER) lumen and are involved in N-glycosylation, glypiation, O-mannosylation, and C-mannosylation of proteins. We generated a membrane topology model of C-man...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20194842
更新日期:2019-09-29 00:00:00
abstract::People with Alzheimer's disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21239318
更新日期:2020-12-07 00:00:00
abstract::The biofilm component poly-N-acetylglucosamine (PNAG) is an important virulence determinant in medical-device-related infections caused by ESKAPE group pathogens including Gram-positive Staphylococcus aureus and Gram-negative Acinetobacter baumannii. PNAG presentation on bacterial cell surfaces and its accessibility f...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21072465
更新日期:2020-04-02 00:00:00
abstract::Trehalose (α-D-glucopyranosyl α-D-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pha...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms160613729
更新日期:2015-06-15 00:00:00
abstract::Long-chain fatty acyl-CoA synthetase (ACSLs) is an essential enzyme for the synthesis of fatty acyl-CoA. ACSL1 plays a key role in the synthesis of triglycerides, phospholipids, and cholesterol esters. BACKGROUND:In the current study, triglyceride content did not increase after overexpression of the ACSL1 gene. METH...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21062044
更新日期:2020-03-17 00:00:00
abstract:BACKGROUND:The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) fr...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20020425
更新日期:2019-01-19 00:00:00
abstract::Compared to other mammalian species, porcine oocytes and embryos are characterized by large amounts of lipids stored mainly in the form of droplets in the cytoplasm. The amount and the morphology of lipid droplets (LD) change throughout the preimplantation development, however, relatively little is known about express...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21186488
更新日期:2020-09-05 00:00:00
abstract::Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms141121727
更新日期:2013-11-01 00:00:00
abstract::We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21218088
更新日期:2020-10-29 00:00:00
abstract::Claudin-1 (CLDN1), a tight junctional protein, is highly expressed in lung cancer cells and may contribute to chemoresistance. A drug which decreases CLDN1 expression could be a chemosensitizer for enhancing the efficacy of anticancer drugs, but there is no such drug known. We found that PMTPV, a short peptide, which ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21165909
更新日期:2020-08-17 00:00:00
abstract::The dysfunction of astrocytic inwardly rectifying potassium (Kir) 4.1 channels, which mediate the spatial potassium-buffering function of astrocytes, is known to be involved in the development of epilepsy. Here, we analyzed the Kir4.1 expressional changes in Leucine-Rich Glioma-Inactivated 1 (Lgi1) mutant rats, which ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20051013
更新日期:2019-02-26 00:00:00
abstract::PCSK9 (Proprotein convertase subtilisin/kexin type 9) increases plasma cholesterol levels by promoting LDL receptor degradation. Current antibody inhibitors block the interaction between PCSK9 and LDL receptors, significantly decrease plasma cholesterol levels, and provide beneficial clinical outcomes. To reduce the a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19020640
更新日期:2018-02-24 00:00:00
abstract::Protein kinase is a novel therapeutic target for human diseases. The off-target and side effects of ATP-competitive inhibitors preclude them from the clinically relevant drugs. The compounds targeting the druggable allosteric sites outside the highly conversed ATP binding pocket have been identified as promising alter...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19010111
更新日期:2018-01-01 00:00:00
abstract::Phosphodiesterases (PDEs) are essential enzymes for the regulation of pathways mediated by cyclic adenosine monophosphate (cAMP). Secondary plant compounds like anthocyanins (ACs) can inhibit PDE activity and, consequently, may be beneficial for lipid metabolism. This study investigated 18 AC-rich juice extracts and p...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21186934
更新日期:2020-09-21 00:00:00
abstract::Stem cells for regenerative medicine purposes offer therapeutic benefits, but disadvantages are still ill defined. The benefit of stem cells may be attributed to their secretion of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs), including exosomes. We present a novel cell-free stem cell-derive...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21249364
更新日期:2020-12-09 00:00:00
abstract::Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malar...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20225574
更新日期:2019-11-08 00:00:00