BMS 470539 (hydrochloride)
目录号 : GC42954BMS 470539 (hydrochloride)是一种高效的选择性黑皮质素1受体（MC-1R）激动剂，在cAMP积累测定中，对人源和鼠源MC1R的EC50值分别为16.8和11.6nM。
Cas No.:2341796-82-3
Sample solution is provided at 25 µL, 10mM.
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BMS 470539 (hydrochloride) is a highly selective and potent melanocortin-1 receptor (MC-1R) agonist. In cAMP accumulation assays, its EC50 values for human and mouse MC1R are 16.8 and 11.6nM, respectively[1]. BMS 470539 (hydrochloride) can be used to study the function of MC1R in physiological and pathological processes such as inflammation, cancer, and pigmentation[2, 3].
In vitro, treatment of C-20/A4 chondrocytes with BMS 470539 (hydrochloride) (10.0µg/mL) for 2h increased intracellular cAMP levels by 2-fold[4].
In vivo, subcutaneous administration of BMS 470539 (hydrochloride) (20mg/kg/day) for 4 weeks significantly alleviated the α-synuclein (αSyn)-induced decrease in striatal dopamine levels in mice treated with αSyn-adenoviral vector (AAV)[5].
References:
[1] Kang L, McIntyre K W, Gillooly K M, et al. A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice[J]. Journal of leukocyte biology, 2006, 80(4): 897-904.
[2] Mun Y, Kim W, Shin D. Melanocortin 1 receptor (MC1R): pharmacological and therapeutic aspects[J]. International journal of molecular sciences, 2023, 24(15): 12152.
[3] Rocliffe H, Austin-Williams S, Krilis G, et al. MC1R reduces scarring and rescues stalled healing in a novel preclinical chronic wound model[J]. bioRxiv, 2022: 2022.11. 30.518516.
[4] Can V C, Locke I C, Kaneva M K, et al. Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes[J]. European Journal of Pharmacology, 2020, 872: 172971.
[5] Cai W, Srivastava P, Feng D, et al. Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson’s disease[J]. Molecular neurodegeneration, 2022, 17(1): 16.
BMS 470539 (hydrochloride)是一种高效的选择性黑皮质素1受体（MC-1R）激动剂，在cAMP积累测定中，对人源和鼠源MC1R的EC50值分别为16.8和11.6nM[1]。BMS 470539 (hydrochloride)能够用于研究MC1R在炎症、癌症和色素沉着等生理及病理过程中的功能[2, 3]。
在体外，BMS 470539 (hydrochloride)（10.0µg/mL）处理C-20/A4软骨细胞2h，使细胞内cAMP水平升高了2倍[4]。
在体内，BMS 470539 (hydrochloride)（20mg/kg/day）通过皮下注射治疗α-突触蛋白（αSyn）腺相关病毒（AAV）处理的小鼠4周，显著减轻了αSyn引起的纹状体多巴胺水平下降[5]。
| Cell experiment [1]: | |
Cell lines | C-20/A4 chondrocyte |
Preparation Method | Cells were treated either 30min prior to (prophylactic regime) or 2h post (therapeutic regime) 0.1µg/mL LPS (E. coli; 111.60) stimulation (concentration selected from preliminary experiments), Phosphate Buffered Saline (PBS) (control), pan human melanocortin MC1 receptor agonist α-MSH (3.0µg/mL), human melanocortin MC3 receptor agonist [DTrp8]-γ-MSH (3.0µg/mL), KPV (4.0µg/mL), human melanocortin MC1 receptor agonist BMS 470539 (hydrochloride) (10.0µg/mL), or selective human melanocortin MC3 receptor agonist PG-990 (3.0µg/mL). Receptor functionality was determined by cAMP accumulation. |
Reaction Conditions | 10.0µg/mL; 30min, 2h |
Applications | The highly selective human melanocortin receptor 1 (MC1R) agonist BMS 470539 (hydrochloride) can increase cAMP accumulation by two-fold. |
| Animal experiment [2]: | |
Animal models | C57Bl/6 J mice |
Preparation Method | Mice were divided into two groups. The experimental group received an intracerebral injection of 3nmol of NDP-MSH (dissolved in 2μL PBS) into the left striatum (coordinates: anterior-posterior+0.9mm, left-right+2.2mm, dorsal-ventral -2.5mm from the skull vertex) at a rate of 30μL/60min. The control group received an injection of PBS. Immediately after the NDP-MSH or control solution injection, alpha-synuclein (αSyn) adeno-associated virus (AAV) was injected into the substantia nigra. Starting from day 1 after αSyn AAV or empty vector injection, BMS 470539 (hydrochloride) (20mg/kg) or an equivalent volume of saline was administered subcutaneously daily for 4 weeks. The mice were then euthanized 16 weeks after AAV injection, and dopamine levels in the striatum were measured. |
Dosage form | 20mg/kg/day; 4 weeks; s.c. |
Applications | αSyn reduced striatal dopamine on the ipsilateral side in saline-treated mice 16 weeks after AAV injection, whereas BMS 470539 (hydrochloride) treatment significantly attenuated the αSyn-induced dopamine deficit. |
References: | |
| Cas No. | 2341796-82-3 | SDF | |
| 化学名 | 1-[1-(3-methyl-L-histidyl-O-methyl-D-tyrosyl)-4-phenyl-4-piperidinyl]-1-butanone, dihydrochloride | ||
| Canonical SMILES | O=C([C@@H](CC1=CC=C(OC)C=C1)NC([C@@H](N)CC2=CN=CN2C)=O)N3CCC(C4=CC=CC=C4)(C(CCC)=O)CC3.Cl.Cl | ||
| 分子式 | C32H41N5O4•2HCl | 分子量 | 632.6 |
| 溶解度 | DMF: 25 mg/ml, DMSO: 10 mg/ml, Ethanol: 20 mg/ml | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5808 mL | 7.9039 mL | 15.8078 mL |
| 5 mM | 316.2 μL | 1.5808 mL | 3.1616 mL |
| 10 mM | 158.1 μL | 790.4 μL | 1.5808 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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- Purity: >99.50%
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