RO27-3225 is a selective melanocortin-4 receptor (MC4R) agonist with EC₅₀ values of 0.6 nM at MC4R, 4.8 nM at MC3R, and >10,000 nM at MC1R and MC5R. [1]
Functions as a potent and selective MC4R agonist. [2][3]

RO27-3225 是一种环状七肽（Ac-Cys¹⁰-[D-Nal⁷,Arg⁸]-Cys⁹-NH₂），对MC4R的选择性比对MC1R/MC5R高1,000倍。 [1]
作用机制：激活MC4R调节中枢食欲调控和外周抗炎通路。 [1][2]
通过促进血管生成和抑制卒中后神经炎症发挥神经保护作用。 [3]

RO27-3225 (1 mg/kg i.p.) did not induce conditioned taste aversion or impair motor coordination in rotarod tests. [1]
No acute toxicity observed at 90 μg/kg i.v. in hemorrhagic shock rats. [2]
No behavioral abnormalities or mortality reported at 0.5 mg/kg i.p. during 14-day treatment in MCAO mice. [3]

Food intake study: Rats/mice received RO27-3225 (0.01, 0.1, 1 mg/kg) or vehicle via intraperitoneal (i.p.) injection. Food consumption was measured 1-4h post-dosing. Taste aversion assessed by sucrose preference after drug pairing. [1]
Hemorrhagic shock model: Rats subjected to 45% blood loss received RO27-3225 (90 μg/kg) or vehicle intravenously at 60 min post-shock. Hemodynamics monitored for 6h; organs harvested for histology/cytokine analysis. [2]
Stroke recovery model: MCAO mice treated with RO27-3225 (0.5 mg/kg i.p. daily for 14 days) starting 24h post-surgery. Brains analyzed by immunohistochemistry and ELISA at day 15. [3]

RO27-3225 (1 mg/kg intraperitoneal injection) did not induce conditioned taste aversion, nor did it impair motor coordination in the rotarod test. [1]
In rats with hemorrhagic shock, no acute toxicity was observed at 90 μg/kg intravenous injection. [2]
In MCAO mice, no behavioral abnormalities or deaths were reported after 14 days of intraperitoneal treatment at 0.5 mg/kg. [3]

[1]. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J Neurosci. 2000 May 1;20(9):3442-8.

[2]. Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage. Br J Pharmacol. 2007 Mar;150(5):595-603.

[3]. Effects of RO27-3225 on neurogenesis, PDGFRβ+ cells and neuroinflammation after cerebral infarction. Int Immunopharmacol. 2020 Feb 11;81:106281.

Studies using non-selective agonists and antagonists of melanocortin-3 receptor (MC3R) and MC4R have demonstrated the important role of the melanocortin system in controlling food intake in the central nervous system. This paper describes a novel compound exhibiting highly selective agonist activity towards the MC4 receptor, while showing minimal activity towards the MC3 receptor. Central injection of this selective agonist into rats increased Fos-like immunoreactivity in the paraventricular nucleus, central amygdala, nucleus of the solitary tract, and posterior pole, a neuronal activation pattern similar to that induced by non-selective MC3/4R agonists. Furthermore, central injection of this compound into rats or peripheral injection into db/db mice lacking functional leptin receptors suppressed food intake through a mechanism without disease or other non-specific effects. Conversely, a related selective MC4R antagonist significantly increased food intake in rats upon central administration. These results support the hypothesis that brain MC4R is closely associated with food intake and weight control, and provide evidence that selective activation of MC4R leading to anorexia is not secondary to an aversion effect. [1]

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Background and Objectives: Melanocortin plays a life-saving role in circulatory shock, which may be mediated by the MC4 receptor. To directly understand the role of the melanocortin MC4 receptor in hemorrhagic shock, we investigated the effects of two novel selective MC4 receptor agonists. Methods: A severe hemorrhagic shock model was established in rats under general anesthesia. Rats were then treated with the non-selective agonist [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH) or the selective MC4 agonists RO27-3225 and PG-931, respectively. Cardiovascular and respiratory function were continuously monitored for 2 hours; survival rate was recorded within 24 hours. Free radicals in the blood were measured by electron spin resonance spectroscopy; tissue damage was histologically assessed at 25 minutes or 24 hours after treatment. Main Results: All rats receiving saline treatment died within 30–35 minutes. NDP-MSH, RO27-3225 and PG-931 treatments all dose-dependently (13-108 nmol kg-1 intravenous injection) restored cardiovascular and respiratory function and improved survival. These three melanocortin agonists also significantly reduced circulating free radical levels compared with saline-treated shock rats. All of these effects could be prevented by pretreatment with the selective MC4 receptor antagonist HS024 via intraperitoneal injection. In addition, RO27-3225 treatment prevented morphological and immunocytochemical changes in the heart, lungs, liver and kidneys in the early (25 min) and late (24 h) stages. Conclusion and significance: Stimulation of MC4 receptors can reverse hemorrhagic shock, reduce multi-organ damage and improve survival. Our results suggest that selective MC4 receptor agonists may have a protective effect against multi-organ failure following circulatory shock. [2] Cerebral infarction imposes a severe social and economic burden on patients due to its high incidence and mortality, and existing treatments are limited. RO27-3225 is a highly selective melanocortin receptor 4 agonist that can alleviate damage caused by various neurological diseases, such as cerebral hemorrhage, traumatic brain injury, and chronic neurodegenerative diseases. However, the effect of RO27-3225 on cerebral infarction remains unclear. This study used a mouse model of transient middle cerebral artery occlusion (tMCAO) and administered RO27-3225 or saline via intraperitoneal injection. Results showed that on day 7 after tMCAO, RO27-3225 increased the number of Nestin+/BrdU+ cells and dicortin (DCX)+/BrdU+ cells in the subventricular zone (SVZ), as well as the number of DCX+/BrdU+ cells in the peri-infarct region. In addition, on day 3 after tMCAO, RO27-3225 reduced the number of activated microglia (Iba1+ cells with a specific morphology) in the peri-infarct area and decreased the expression levels of Iba1, TNFα, IL6 and iNOS proteins, while increasing the number of PDGFRβ+ cells. Finally, mice treated with RO27-3225 showed a significant reduction in infarct volume, brain water content and neurological deficits after cerebral infarction. Therefore, RO27-3225 can improve the prognosis after cerebral infarction, partly through regulating neurogenesis in the SVZ, survival of PDGFRβ+ cells and neuroinflammation in the peri-infarct area. Our study suggests that RO27-3225 is a potential new therapy for cerebral infarction. [3]

C39H52N12O6

784.906987190247

898.406

1373926-49-8

274682-89-2;1057258-86-2 (free base isomer);1373926-49-8 (TFA);1051970-60-5 (3 TFA);

146026285

Typically exists as solid at room temperature

326

10

13

22

64

1470

4

CCCC(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)N(C)CC(=O)N.C(=O)(C(F)(F)F)O

XBNXUPIBUGBMCO-WYDLTDSDSA-N

InChI=1S/C39H52N12O6.C2HF3O2/c1-3-10-34(53)47-31(19-26-21-43-23-46-26)37(56)49-30(17-24-11-5-4-6-12-24)36(55)48-29(15-9-16-44-39(41)42)35(54)50-32(38(57)51(2)22-33(40)52)18-25-20-45-28-14-8-7-13-27(25)28;3-2(4,5)1(6)7/h4-8,11-14,20-21,23,29-32,45H,3,9-10,15-19,22H2,1-2H3,(H2,40,52)(H,43,46)(H,47,53)(H,48,55)(H,49,56)(H,50,54)(H4,41,42,44);(H,6,7)/t29-,30-,31-,32-;/m0./s1

(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)-methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[[(2S)-2-[[(2S)-2-(butanoylamino)-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanamide;2,2,2-trifluoroacetic acid

RO27-3225; 1373926-49-8; RO273225; RO27-3225; (2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)-methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[[(2S)-2-[[(2S)-2-(butanoylamino)-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanamide;2,2,2-trifluoroacetic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。