glucose tolerance

CCG-1423, a selective RhoA pathway inhibitor, suppresses SRF-mediated transcription.

AMPK activator 4 is a potent and selective AMPK activator that does not inhibit mitochondrial complex I. It selectively activates AMPK in muscle tissue, dose-dependently improves glucose tolerance in normal mice, significantly reduces fasting glucose levels, and improves insulin resistance in db/db diabetic mice. [AMPK activator 4 has hypoglycemic effects.]

Phanginin A, a natural product discovered in Caesalpinia sappan Linn, activates SIK1 and inhibits gluconeogenesis in mouse primary hepatocytes. Phanginin A increases PDE4 activity and suppresses the hepatic cAMP/PKA/CREB pathway, improving metabolic disorders in ob/ob mice. It may be used in studies of type 2 diabetes.

trans-Cinnamic acid (Myricitrine) exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

Oxfenicine (4-Hydroxy-L-phenylglycine) is a carnitine palmitoyltransferase-1 inhibitor. Oxfenicine improves whole-body glucose tolerance and insulin sensitivity in high-fat diet-induced obese mouse with insulin resistance.

SR 1903 is an inverse agonist of RORγ and PPARγ (IC₅₀ = 100 nM and 209 nM, respectively) and an agonist of LXR (EC₅₀ = 154 nM). It exerts anti-inflammatory and anti-diabetic effects in mouse models of collagen-induced arthritis and diet-induced obesity.

HWL-088 is a potent free fatty acid receptor 1 (FFA1/GPR40) agonist. HWL-088 significantly improves glucose tolerance in normal and diabetic models.

KPLH1130, a specific pyruvate dehydrogenase kinase (PDK) inhibitor, enhances glucose tolerance in mice fed a high-fat diet (HFD). It effectively hinders macrophage polarization and mitigates proinflammatory reactions.

PF-5006739 is a potent and selective CK1δ/ε inhibitor with IC50 values of 3.9 nM and 17.0 nM, respectively.It can be used in the study of psychiatric disorders and exhibits low nanomolar in vitro potency against CK1δ/ε and high kinome selectivity.PF-5006739 dose-dependently reduces opioid-seeking behavior in rodent relapse models and improves glucose tolerance in mouse models of diet-induced obesity (DIO) and genetic obesity (ob/ob).

SX29 is a non-competitive α-glucosidase inhibitor with oral activity, exhibiting an IC50 of 2.12 μM. It possesses hypoglycemic properties; oral administration of SX29 reduces blood glucose levels and enhances glucose tolerance in diabetic mice.

YH18968, a GPR119 agonist, improves glucose tolerance and enhances blood glucose-lowering effects. When combined with dipeptidyl peptidase-4 (DPP-4) inhibitors, YH18968 increases the plasma levels of active GLP-1 in normal mice.

KOTX1 is an orally active and selective inhibitor of ALDH1A3. In a diabetic mouse model, KOTX1 improves glucose tolerance, insulin secretion, and blood glucose levels.

α-Glucosidase-IN-77 (Compound H7) is a non-competitive α-glucosidase inhibitor with an IC50 of 1.25 μM. It reduces blood glucose levels, improves glucose tolerance, regulates gut microbiota, and exhibits hepatoprotective effects in a mouse model of type 2 diabetes.

PPARγmodulator-2 (Compound (R)-2n) is a reversible modulator of PPARγ, inhibiting the PPARγ ligand-binding domain (LBD) with an IC50 of 41 nM. It helps lower blood glucose levels, improves glucose tolerance and insulin sensitivity, and demonstrates antidiabetic activity in db/db mouse models.

α-Glucosidase-IN-86 (Compound A4) is an orally active α-glucosidase inhibitor with an IC50 of 2.72 μM. In mice, it demonstrates high safety and effectively reduces fasting blood glucose levels, improves glucose tolerance, regulates blood lipids, and exhibits antioxidant properties in diabetic models. α-Glucosidase-IN-86 is suitable for diabetes research.

GLP-1R agonist 30 is an orally active, selective GLP-1R agonist with an EC50 of 0.048 nM. It exhibits outstanding selectivity, with EC50 values exceeding 20 μM for GLP-2R, GIPR, and GCPR. GLP-1R agonist 30 significantly enhances cAMP stimulation and reduces hERG inhibition. The compound has good absorption and excellent β-arrestin pathway selectivity. Additionally, GLP-1R agonist 30 improves glucose tolerance and promotes insulin secretion in B-hGLP1R gene knock-in mice.

ZP3022 is a dual agonist targeting the glucagon-like peptide 1 receptor (GLP-1R) and cholecystokinin 2 (CCK2) receptor. It selectively enhances cAMP accumulation or ERK phosphorylation in HEK293 cells with GLP-1R or CCK2 receptor expression, compared to ERK phosphorylation in cells with the CCK1 receptor (EC50s: 0.02, 10.3, and >1,000 nM for human receptors, respectively). At 40 nM, ZP3022 promotes proliferation of rat neonatal β-cells in vitro. It also boosts glucose-induced insulin secretion (GSIS) in rat pancreatic islets at 10 and 100 nM concentrations and decreases body weight in rats at 40 nmol/kg doses twice daily. Administered at 100 nmol/kg daily, ZP3022 enhances β-cell and total pancreatic mass and improves glucose tolerance in db/db mice, while reducing food intake but not body weight in these mice.

Tryptophan-cholic acid (Trp-CA) is a microbial amino acid-binding bile acid (MABA), serving as an endogenous ligand and agonist for MRGPRE (Mas-related GPCR family member E), thereby inducing GLP-1 secretion. Tryptophan-cholic acid improves glucose tolerance in diabetic mice and may be utilised for studies on type 2 diabetes.

α-Glucosidase-IN-49 (compound C23) is a potent inhibitor of α-Glucosidase, with an IC50 of 0.52 μM. This compound exhibits oral bioactivity, effectively lowering blood glucose levels and enhancing glucose tolerance in mice.

ZLN005 (hydrochloride) is an activator of the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). It enhances the expression of PGC-1α and downstream genes in skeletal muscle cells, leading to improved glucose utilization and fatty acid oxidation. In diabetic db/db mice, ZLN005 (hydrochloride) elevates the transcription of PGC-1α and downstream genes in skeletal muscle, boosts fat oxidation, and enhances glucose tolerance, pyruvate tolerance, and insulin sensitivity.

LCZ960 is an orally active glucokinase (GK) activator that stimulates GK activity in liver cells in vitro and enhances glucose uptake in vivo by activating hepatic GK. It effectively lowers blood glucose levels in diet-induced obesity (DIO) in mice. LCZ960 maintains normal blood sugar and improves glucose tolerance in DIO mice and rats. Additionally, LCZ960 stimulates glycogen synthase flux and increases glycogen turnover in the liver of rats, inducing an increase in hepatic glycogen cycling. This compound is useful for research on obesity and type 2 diabetes induced by high-fat diets.

Gosogliptin hydrochloride is the hydrochloride salt of Gosogliptin. Gosogliptin (PF-00734200) is a potent, orally active selective competitive inhibitor of DPP-IV, which is primarily responsible for degrading the incretin hormones GLP-1 and glucose-dependent insulinotropic polypeptide. Gosogliptin rapidly and reversibly inhibits plasma DPP-4 activity, stimulates insulin secretion, and improves glucose tolerance.

VSP-77 is an orally active PPARγ agonist. It selectively enhances the expression of insulin sensitivity-related genes (Glut4 and Adiponectin) by inhibiting CDK5-mediated phosphorylation of PPARγ at Ser-273. In a high-fat diet-induced diabetic mouse model, VSP-77 significantly improves glucose tolerance and reduces fasting blood glucose and insulin levels. VSP-77 is applicable for diabetes research.

CB1 antagonist6 (Compound 11jE2) is an orally active CB1R antagonist with an IC50 value of 23 nM. It significantly reduces food intake and body weight in diet-induced obesity (DIO) mice, improves glucose tolerance and insulin resistance, and lowers serum ALT and AST levels, demonstrating hepatoprotective effects. CB1 antagonist6 is applicable for studies on metabolic syndrome, including obesity and diabetes.