CGRP Receptor Agonist

Cagrilintide is an investigational novel long-acting acylated amylin analogue, acts as nonselective amylin receptors (AMYR) and calcitonin G protein-coupled receptor (CTR) agonist. Cagrilintide induces significant weight loss and reduces food intake. Cagrilintide has the potential for the research of obesity.

Calcitonin salmon, a calcium regulating hormone, is a dual-action amylin and calcitonin receptor agonist, could stimulate bone formation and inhibit bone resorption.

CTR/AMYR modulator-2 (Example 107) is a receptor 3 for pancreatic amyloid peptide (bAMY3R) agonist, and its EC₅₀ for stimulating cAMP production in cells is ＜500 nM. CTR/AMYR modulator-2 is also a receptor for calcitonin (bCTR) agonist, with its EC₅₀ being ＜5000 nM. CTR/AMYR modulator-2 can be used for research on type 2 diabetes and obesity.

KBP-089 is a dual Amylin and Calcitonin Receptor agonist. KBP-089 reduces body weight, decreases adipose tissue mass and improves glucose tolerance in obese rats. KBP-089 also eliminates lipid accumulation in the liver and muscle, and ameliorates glycemic homeostasis and insulin sensitivity. KBP-089 is applicable to the research of diseases such as obesity and type 2 diabetes.

Cagrilintide acetate is a non-selective AMYR/CTR agonist and long-acting acylated amylase analogue. Cagrilintide acetate causes a reduction in food intake and significant weight loss in a dose-dependent manner. Cagrilintide acetate can be used in obesity studies.

Calcitonin (human) is a hypocalcemic hormone. Calcitonin can lower blood calcium levels and inhibit bone resorption. Calcitonin can be used in hypercalcemia or osteoporosis research.

9-PAHSA is an orally active endogenous GPR120 agonist (EC₅₀=18 μM). 9-PAHSA significantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSA induces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSA regulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSA does not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSA can be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.

SUN B8155, a non-peptide agonist of calcitonin (CT) receptor, selectively mimics the biological actions of calcitonin. Calcitonin, a 32-amino acid peptide hormone secreted mainly from the thyroid gland, plays an important role in maintaining bone homeostasis.

PHM-27 (human) is a human prepro-vasoactive intestinal polypeptide (27 amino acid). PHM-27 (human) is a potent the human calcitonin receptor agonist with an EC₅₀ of 11 nM. PHM-27 (human) efficiently enhances glucose-induced insulin secretion from beta cells by an autocrine mechanism.

Colulintide (LY3541105) is an amylin-calcitonin dual receptor agonist with Amylin as its scaffold. Colulintide is applicable to research related to type 2 diabetes and obesity.

Davalintide is an Amylin (HY-P1464)-mimetic peptide with greater potency and longer-lasting effects. Davalintide is a potent agonist of amylin receptor (IC₅₀ = 0.04 nM), calcitonin receptor (IC₅₀ = 0.06 nM) and calcitonin related peptide receptor (CGRP receptor) (IC₅₀ = 3.1 nM). Davalintide shows stronger potency to Amylin to activate cyclic AMP production through the calcitonin receptor (EC₅₀ = 1.4 nM). Davalintide regulates blood sugar and weight through various mechanisms such as delaying gastric emptying, inhibiting glucagon secretion, and reducing food intake. Davalintide can be used for the studies of anti-obesity and anti-diabetes.

Kendomycin ((−)-TAN 2162) is a polyketide antibiotic with remarkable antibacterial and cancer cells cytotoxic activities. Kendomycin tends to be bacteriostatic rather than bactericidal and inhibits the growth of the methicillin-resistant Staphylococcus aureus (MRSA) strain COL at a low concentration (MIC of 5 μg/mL). Kendomycin is a potent antagonist of the endothelin receptor and a calcitonin receptor agonist which plays its role as an anti-osteoporotic agent.

9-PAHSA-¹³C₄ is ¹³C-labeled 9-PAHSA. 9-PAHSAis an orally active endogenous GPR120 agonist (EC₅₀=18 μM). 9-PAHSAsignificantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSAinduces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSAregulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSAdoes not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSAcan be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.

Calcitonin-¹³C₆,¹⁵N₄ (salmon) (Salmon calcitonin-¹³C₆,¹⁵N₄) TFA is ¹³C and ¹⁵N-labeled Calcitonin (salmon) (HY-P0090). Calcitonin (salmon) , a calcium regulating hormone, is a dual-action amylin and calcitonin receptor agonist, could stimulate bone formation and inhibit bone resorption.

Biotinyl-Amylin (human) is a biotin-labeled derivative of Amylin, amide, human (HY-P1070). Biotinyl-Amylin (human) acts as a competitive agonist for the Calcitonin Receptor (CTR) and for the Amylin receptors (AMY₁, AMY₂, and AMY₃) formed by the association of CTR with RAMP1/2/3. By mimicking endogenous human amylin, Biotinyl-Amylin (human) binds to and activates CTR and AMY receptors, thereby initiating downstream signaling pathways involving cAMP, CREB, and ERK1/2, while retaining high-affinity receptor binding and activation capabilities. Biotinyl-Amylin (human) is primarily utilized in studies investigating the metabolic regulatory mechanisms underlying obesity and diabetes; it is also applicable to pharmacological research, receptor localization studies, and ligand-binding assays related to Amylin receptors in the context of Alzheimer's disease.

9-PAHSA-d9 is the deuterium labeled 9-PAHSA (HY-120657). 9-PAHSA is an orally active endogenous GPR120 agonist (EC₅₀=18 μM). 9-PAHSA significantly inhibits LPS-induced inflammatory responses by blocking the NF-κB pathway. 9-PAHSA induces adipocyte browning, enhances glucose uptake and reduces lipid accumulation, while improving mitochondrial function and the survival rate of steatotic hepatocytes. In terms of neuroprotection, 9-PAHSA regulates the expression of REST and BDNF in the prefrontal cortex of diabetic mice, and effectively prevents spatial working memory deficits and abnormal social behaviors. 9-PAHSA does not directly regulate insulin secretion or improve systemic insulin sensitivity, and possesses specific anti-inflammatory, metabolic regulatory and neuroprotective properties. 9-PAHSA can be used in the research of diabetes-related cognitive impairment, obesity and non-alcoholic fatty liver disease.

AMYR/CTR agonist 1 (Compound 195) is a pancreatic amylin receptor and calcitonin receptor (AMYR/CTR) agonist with EC₅₀ values for pancreatic amylin receptor and calcitonin receptor cAMP of 99.5 and 6.16 pM respectively. AMYR/CTR agonist 1 can be used in the research of diseases such as type 2 diabetes and obesity.

rel-CTR/AMYR agonist-1 (Example 169) is an agonist of amylin and/or calcitonin receptor.

Cizolirtine citrate (E-4018) is an analgesic agent. Cizolirtine citrate has significant analgesic and anti-hyperalgesic action in neuropathic pain models.

TPM004 is an ultralong-acting, nonaggregating dual amylin (AMY3R) and calcitonin receptor (CTR) agonist with EC₅₀ values of 0.5 and 0.7 pM. TPM004 induces weight loss, attenuates adiposity rebound, lowers glucose, and improves glucose homeostasis. TPM004 can be used for the research of obesity, diabetes.