NNC0165-1273 acetate is a selective NPY Y2 receptor agonist with a K i of 2 nM and an EC 50 of 5.0 nM. NNC0165-1273 acetate blocks Ghrelin-induced cFos expression. NNC0165-1273 acetate reduces nocturnal food intake, attenuates feeding behavior, induces early satiety, and causes dose-dependent decreases in body weight and fat mass in diet-induced obese mice. When used in combination with Semaglutide, NNC0165-1273 acetate reduces preference for high-fat diet, promotes body weight loss, and produces sustained weight loss effects in diet-induced obese rats. NNC0165-1273 acetate can be used in studies related to diet-induced obesity [1] [2] [3].
In Vivo, NNC0165-1273 (0.03-1 μmol/kg/d; subcutaneous injection; continuous infusion; 14 days) acetate causes dose-dependent reductions in food intake, body weight, and fat mass in diet-induced obese male C57BL/6 mice, with the highest dose reducing fat mass by approximately 31%[1]. NNC0165-1273 (0.04-1 μmol/kg; subcutaneous injection; single administration) acetate potently inhibits ghrelin-induced feeding behavior in healthy male C57BL/6 mice, with the 0.04 μmol/kg dose almost completely blocking the orexigenic effect of ghrelin at 1 and 2 hours[1]. Combined administration of NNC0165-1273 (0.08 µmol/kg/d; osmotic minipump; continuous infusion) acetate and Semaglutide achieves a maximum body weight loss of 23.9% in diet-induced obese male Wistar rats, an effect superior to that observed with Roux-en-Y gastric bypass surgery in previous studies[3]. Co-administration of NNC0165-1273 (0.04 µmol/kg/d; subcutaneous injection; continuous administration) acetate, NNC0165-0020 and Semaglutide reduces the body weight of male Wistar rats with high-fat diet-induced obesity by a maximum of 20.5% and persistently decreases their preference for high-fat diet[2].
In Vitro, NNC0165-1273 acetate exhibits high selectivity for the Y2 receptor (>5000-fold over the Y1 receptor, 1250-fold over the Y4 receptor, and 650-fold over the Y5 receptor)[1]. NNC0165-1273 acetate is a highly selective Y2 receptor agonist, with a binding Ki of 2.0 nM and a functional EC50 of 5.0 nM for the Y2 receptor, and exhibits low activity against Y1, Y4 and Y5 receptors[2]. The in vitro half-life of NNC0165-1273 acetate (570 min) is 2.85 times longer than that of PYY3-36, indicating greater metabolic stability[2].
References:
[1]. Jones ES, et al. Modified Peptide YY Molecule Attenuates the Activity of NPY/AgRP Neurons and Reduces Food Intake in Male Mice. Endocrinology. 2019 Nov 01;160(11):2737-2747.
[2]. Oertel M, et al. GLP-1 and PYY for the treatment of obesity: a pilot study on the use of agonists and antagonists in diet-induced rats. Endocrine connections. 2024 Mar 01;13(3):e230398.
[3]. Oertel M, et al. Effects of a combinatory treatment with semaglutide and a NPY Y2 receptor selective PYY 3-36 analogue in diet-induced obese rats: surpassing bariatric surgery?[C]//Endocrine Abstracts. Bioscientifica, 2023, 90.
In Vivo, NNC0165-1273 (0.03-1 μmol/kg/d; subcutaneous injection; continuous infusion; 14 days) acetate causes dose-dependent reductions in food intake, body weight, and fat mass in diet-induced obese male C57BL/6 mice, with the highest dose reducing fat mass by approximately 31%[1]. NNC0165-1273 (0.04-1 μmol/kg; subcutaneous injection; single administration) acetate potently inhibits ghrelin-induced feeding behavior in healthy male C57BL/6 mice, with the 0.04 μmol/kg dose almost completely blocking the orexigenic effect of ghrelin at 1 and 2 hours[1]. Combined administration of NNC0165-1273 (0.08 µmol/kg/d; osmotic minipump; continuous infusion) acetate and Semaglutide achieves a maximum body weight loss of 23.9% in diet-induced obese male Wistar rats, an effect superior to that observed with Roux-en-Y gastric bypass surgery in previous studies[3]. Co-administration of NNC0165-1273 (0.04 µmol/kg/d; subcutaneous injection; continuous administration) acetate, NNC0165-0020 and Semaglutide reduces the body weight of male Wistar rats with high-fat diet-induced obesity by a maximum of 20.5% and persistently decreases their preference for high-fat diet[2].
In Vitro, NNC0165-1273 acetate exhibits high selectivity for the Y2 receptor (>5000-fold over the Y1 receptor, 1250-fold over the Y4 receptor, and 650-fold over the Y5 receptor)[1]. NNC0165-1273 acetate is a highly selective Y2 receptor agonist, with a binding Ki of 2.0 nM and a functional EC50 of 5.0 nM for the Y2 receptor, and exhibits low activity against Y1, Y4 and Y5 receptors[2]. The in vitro half-life of NNC0165-1273 acetate (570 min) is 2.85 times longer than that of PYY3-36, indicating greater metabolic stability[2].
References:
[1]. Jones ES, et al. Modified Peptide YY Molecule Attenuates the Activity of NPY/AgRP Neurons and Reduces Food Intake in Male Mice. Endocrinology. 2019 Nov 01;160(11):2737-2747.
[2]. Oertel M, et al. GLP-1 and PYY for the treatment of obesity: a pilot study on the use of agonists and antagonists in diet-induced rats. Endocrine connections. 2024 Mar 01;13(3):e230398.
[3]. Oertel M, et al. Effects of a combinatory treatment with semaglutide and a NPY Y2 receptor selective PYY 3-36 analogue in diet-induced obese rats: surpassing bariatric surgery?[C]//Endocrine Abstracts. Bioscientifica, 2023, 90.