BMS 470539 (hydrochloride)

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 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:
[1] 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.
[2]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.