TGR5 Receptor Agonist 3 (Compound 19) is a soft-drug G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) agonist with reduced gallbladder-filling effects (favorable gallbladder safety), with EC50s of 16.4 and 209 nM for hTGR5 and mTGR5, respectively[1].
UDP-GlcNAz disodium is a substrate for UDP-GlcNAc:polypeptidyltransferase[1].
NTU281 is a potent transglutaminase-2 inhibitor. NTU281 can reduce the increases in serum creatinine and albuminuria in diabetic rats. NTU281 can also reduce glomerular collagen I accumulation, Hic-5 and α-SMA expression, and apoptosis. NTU281 can be used for researching glomerulosclerosis caused by diabetes[1][2].
O-Nornuciferine, an aporphine-type alkaloid from lotus leaf, is a potent hERG channel inhibitor[1].
AZD7545 is a novel, selective small-molecule inhibitor of PDHK2 (PDH kinase2) with an IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2 respectively.IC50 Value: 36.8 nM (PDHK1); 6.4 nM (PDHK2) [1]Target: PDHK1/2in vitro: The IC50 values for inhibition of PDHK2 and PDHK1 by AZD7545 were 6.4 ± 2.2 nM (n = 6) and 36.8 ± 18 nM (n = 3) respectively. Other compounds in this series inhibited both PDHK1 and PDHK2 and a consistent trend of reduced potency (5-15-fold) towards PDHK1, as compared with PDHK2, was observed. In contrast, AZD7545 and related compounds failed to inhibit PDHK4 and paradoxically, at higher concentrations (>10 nM), AZD7545 stimulated PDHK4 activity [1]. In the presence of PDHK2, AZD7545 increased PDH activity with an EC(50) value of 5.2 nM. In rat hepatocytes, the rate of pyruvate oxidation was stimulated 2-fold (EC(50) 105 nM) [2].in vivo: A single dose of AZD7545 to Wistar rats increased the proportion of liver PDH in its active, dephosphorylated form in a dose-related manner from 24.7 to 70.3% at 30 mg/kg; and in skeletal muscle from 21.1 to 53.3%. A single dose of 10 mg/kg also significantly elevated muscle PDH activity in obese Zucker (fa/fa) rats. Obese, insulin-resistant, Zucker rats show elevated postprandial glucose levels compared with their lean counterparts (8.7 versus 6.1 mM at 12 weeks old). AZD7545 (10 mg/kg) twice daily for 7 days markedly improved the 24-h glucose profile, by eliminating the postprandial elevation in blood glucose [2]. An interestingobservation is that administration of maximally effective doses of AZD7545 and related compounds to rats results in the near-complete activation of PDH activity in liver, where PDHK2 is the major isoenzyme, while only partial activation of PDH activity is achieved in skeletal muscle and heart, tissues which express high levels of PDHK4. For example, following administration of a maximally effective dose of compound K (30 mg/kg) the percentage of PDH present in the active (dephosphorylated) state in liver is elevated from 35.3 ± 4.0% to 90.2 ± 2.2% while in skeletal muscle and heart PDH activity plateaus at 64.3 ± 2.3% and 61.8 ± 4.3% respectively. Further evidence for a link between in vitro isoenzyme selectivity and in vivo activity comes from the observation that in fasted rats the ability of AZD7545 toelevate PDH activity in liver is intact, while the activation of skeletal muscle PDH activity in response to the compound is severely blunted [1].
γ-Glutamyl-S-allylcysteine (L-γ-Glutamyl-(S)-Allyl-Cysteine) is a naturally occurring organosulfur compound found in garlic. γ-Glutamyl-S-allylcysteine has antiglycative effect and shows radical-scavenging and metal-chelating capacities[1][2].
BRD 0476 (ML187) is a selective, moderate inhibitor of ubiquitin-specific peptidase 9X (USP9X), inhibits pancreatic β-cell apoptosis that inhibits IFN-γ-induced JAK2 and STAT1 signaling to promote β-cell survival; does not has kinase inhibitory activity, and no effect no effect on JAK1, JAK2, or JAK3 activities, and the deubiquitinase ubiquitin-specific peptidase 9X (USP9X) is an intracellular target of BRD0476.
6-Formylpterin is an inhibitor of Xanthine Oxidase. 6-Formylpterin induces intracellular ROS generation and apoptosis in HL-60 cells. 6-Formylpterin suppresses cell proliferation in PanC-1 cells[1].
PTP1B-IN-4 is a non-competitive allosteric inhibitor of the protein tyrosine phosphatase PTP1B, with an IC50 of 8 μM. PTP1B-IN-4 is potentail for the research of obesity and diabetes[1][2].
2-O-β-D-Glucopyranosyl-L-ascorbic acid (AA-2βG), isolated from Lycium Fruit, is a stable vitamin C analog with anti-tumor activity[1].
Neuropeptide Y (3-36) (human, rat), a neuropeptide Y (NPY) metabolite formed from dipeptidyl peptidase-4 (DPP4), is a selective Y2 receptor agonist. Neuropeptide Y (3-36) (human, rat) is a NPY metabolite formed from dipeptidyl peptidase-4 (DPP4). Neuropeptide Y (3-36) (human, rat) decreases release of norepinephrine via the Y2 receptor[1][2].
Peptide YY (PYY) (3-36), human is a gut hormone peptide that acts as a Y2 receptor agonist to reduce appetite.
Cochliodinol (compound 1) is a metabolite derived from the Apis mellifera ligustica. Cochliodinol has strong free radical scavenging activity of 2, 2-diphenyl-1-picrohydrazine (DPPH) (IC50=3.06 μg/mL)[1].
Ginsenoside Rg4 is a major protopanaxatriol type ginsenoside isolated from the leaves of Panax ginseng C. A. Meyer. The protopanaxatriol type ginsenosides (such as Ginsenoside Rg4) exhibits various biological activities including anti-septic, anti-diabetic, wound healing, immune-stimulatory, and anti-antioxidant activity[1][2].
10(E)-Pentadecenoic Acid (trans-10-Pentadecenoic acid) is a long-chain monounsaturated fatty acid containing 15 carbons[1].
PPARδ agonist is a PPARδ agonist extracted from patent US20180071304, compound example 10.
PPARδ agonist 9 (compound 21) is a PPARδ agonist (EC50: 3.6 nM). PPARδ agonist 9 has in vivo efficacy, reducing serum levels of MCP-1 in mice and significantly inhibiting atherosclerosis progression in the LDLr-KO model (inhibition rate: 50-60%)[1].
Gemcadiol is a potent antilipemic agent. Gemcadiol has the potential for the research of hyperlipoproteinemia[1][2].
TUG-770 is a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist with EC50 of 6 nM for hFFA1.IC50 Value: 6 nM (hFFA1, EC50) [1]Target: GPR40in vitro: TUG-770 (Compound 22) displayed excellent physicochemical and in vitro ADME properties, with good aqueous solubility, good chemical stability, low lipophilicity, and decreased plasma protein binding (PPB). TUG-770 furthermore showed excellent stability toward human liver microsomes (HLM), no inhibition of selected CYP-enzymes implicated in drug-drug interactions, no P-glycoprotein (P-gp) inhibition, and good permeability in the Caco-2 cell assay [1].in vivo: Examination of TUG-770 in an acute intraperitoneal glucose tolerance test (IPGTT) in normal mice revealed a good dose dependent response with maximal reduction in glucose level reached at 50 mg/kg. The effect of TUG-770 was fully sustained after 29 days of daily oral treatment. Additional evaluation of TUG-770 in rats confirmed a significant glucose lowering effect for the high doses already after 10 min and for all doses after 30 min [1].Clinical trial:
Glucagon is a peptide hormone that helps regulate the blood sugar (glucose) levels in the body.
Lerodalcibep (LIB003) is a recombinant fusion protein of a PCSK9-binding domain (adnectin) and human serum albumin. Lerodalcibep is a Lipid-lowering agent. Lerodalcibep can be used for the research of hypercholesterolemia and cardiovascular diseases[1].
Arimoclomol citrate (BRX-220 citrate) is a co-inducer of heat shock proteins (HSP)[1]. Arimoclomol citrate protects motor neurons by enhancing Hsp expression, thus directly affecting protein aggregation and clearance of misfolded assemblies via the proteasome-ubiquitin system[2].
Caulophyllogenin is a triterpene saponin extracted from M. polimorpha. Caulophyllogenin is a partial PPARγ agonist, with an EC50 of 12.6 μM. Caulophyllogenin can be used for the research of type-2 diabetes, obesity, metabolic syndrome and inflammation[1][2].
2,4-Dihydroxybenzaldehyde is an endogenous metabolite.
Org 25935 is a potent and selective glycine transporter 1 protein (GlyT1) inhibitor with an IC50 value of 100 nM. Org 25935 can decrease ethanol (EtOH) intake and EtOH preference in rats, whereas water intake is unaffected. Org 25935 can be used for researching alcohol dependence or abuse[1].
Resolvin D1 methyl ester (RvD1 methyl ester) is the methyl ester of Resolvin D1 (HY-125527). Resolvin D1 methyl ester reduces triglyceride levels[1].
Diosbulbin D is a potential hepatotoxic compound that can be isolated from Dioscorea bulbifera L.. Diosbulbin D induces apoptosis in L-02 cells[1].
Oil Red O is a fat-soluble diazol dye, with a maximum absorption at 518 nm. Oil Red O stains neutral lipids and cholesteryl esters but not biological membranes. Oil Red O can be used for detecting and quantifying hepatic steatosis in mouse liver biopsies. Oil Red O staining efficiently helps to visualize the radical changes that occur in tissues as metabolic disease occurs and progresses[1].
Malabaricone B, a naturally occurring plant phenolic, is an orally active α-glucosidase inhibitor with an IC50 of 63.7 µM. Malabaricone B has anticancer, antimicrobial, anti-oxidation and antidiabetic activities[1][2][3].
FOY 251 free base is an anti-proteolytic active metabolite camostate (HY-13512), acts as a proteinase inhibitor[1].