Cotadutide acetate (MEDI0382 acetate) is a potent peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptor with EC₅₀ values of 6.9 pM and 10.2 pM, respectively. Cotadutide acetate (MEDI0382 acetate) exhibits ability to facilitate both weight loss and glycaemic control, has the potential for obesity and type 2 diabetes (T2D) treatment^[1].

EC50: 6.9 pM (GLP-1); 10.2 pM (glucagon receptor)^[1]

Cotadutide acetate (MEDI0382 acetate) shows EC₅₀ values of 6.9 and 10.2 pM as measured by cAMP generation in CHO cells over‐expressing human recombinant GLP‐1 or glucagon receptors in the presence of 0.1% BSA, which are within 10‐fold of the native ligands^[1].
Cotadutide acetate (MEDI0382 acetate) stimulates a concentration‐dependent increase in cAMP accumulation in rat (INS‐1 832/3) and human (EndoC‐βH1) pancreatic β‐cell lines (EC₅₀=226 pM, 1051 pM, respectively ), as well as rat, mouse and human hepatocytes (462 pM, 840 pM, 1447 pM, respectively)^[1].
Cotadutide acetate (MEDI0382 acetate) has relative potency against GLP‐1R and GCGR activity in human, cynomolgus monkey, mouse and rat transfected GLP‐1 (GLP‐1R) or glucagon (GCGR) receptors expressed CHO cells, The EC₅₀ values are 188 pM, 682 pM; 5.2 pM, 318 pM; 74 pM, 614 pM; and 50 pM, 24173 pM for Human, monkey, mouse and rat GLP‐1R and GCGR activities, respectively^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cotadutide acetate (MEDI0382 acetate) (subcutaneous injection; 10 nmol/kg; once) robustly suppresses food intake in DIO mice relative to vehicle‐treated controls during 0‐12 hours after administration. Mean food intake is reduced during this time interval to approximately 31% of control mice treated with vehicle. The effect of MEDI0382 is evident early (0‐2 hours postdose), the terminal plasma half‐life of MEDI0382 in mice after subcutaneous administration is approximately 5 hours^[1].
Cotadutide acetate (MEDI0382 acetate) (subcutaneous injection; 10 or 30 nmol/kg; once daily; 14-16 weeks) reduces body weight. reduced body weight.The mean body weight of vehicle‐treated animals increased by 2.5% of starting body weight over the course of the 4‐week study, whereas the mean body weight loss is 21%, 30% of starting body weight at dose levels of 10 nmol/kg MEDI0382, 30 nmol/kg MEDI0382, respectively ^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

3788.14

C₁₆₉H₂₅₆N₄₂O₅₇

1′-{palmtoyl-Glu}; His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Lys-Ser-Glu-Tyr-Leu-Asp-Ser-Glu-Arg-Ala-Arg-Asp-Phe-Val-Ala-Trp-Leu-Glu-Ala-Gly-Gly (Amide bridge: Glu1′-Lys10)

1′-{palmtoyl-Glu}; HSQGTFTSDKSEYLDSERARDFVAWLEAGG (Amide bridge: Glu1′-Lys10)

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80deg;C, 6 months; -20deg;C, 1 month (sealed storage, away from moisture)

DMSO : 12.5 mg/mL (3.30 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (insoluble)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂：;10% DMSO ;; 40% PEG300 ;; 5% Tween-80 ;; 45% saline

  Solubility: 1.25 mg/mL (0.33 mM); Suspended solution; Need ultrasonic

  此方案可获得 1.25 mg/mL (0.33 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂：;10% DMSO ;; 90% (20% SBE-β-CD in saline)

  Solubility: 1.25 mg/mL (0.33 mM); Suspended solution; Need ultrasonic

  此方案可获得 1.25 mg/mL (0.33 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂：;10% DMSO ;; 90% corn oil

  Solubility: ≥ 1.25 mg/mL (0.33 mM); Clear solution

  此方案可获得 ≥ 1.25 mg/mL (0.33 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Henderson SJ,et al. Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.Diabetes Obes Metab. 2016 Dec;18(12):1176-1190.