MLS6585

MLS6585 is a selective D1 dopamine receptor (D1R) positive allosteric modulator that enhances Dopamine (HY-B0451)-stimulated G protein/β-arrestin signaling and affinity without intrinsic D1R agonist activity. MLS6585 is inactive at D2R, D3R, D4R, and β2-adrenergic receptors. MLS6585 partially restores signaling of loss-of-function DRD1 variants and enhances responses to multiple agonists^[1][2][3][4]. In Vitro:MLS6585 (50 µM; 90 min) is a low-micromolar-affinity orthosteric allosteric modulator of D1R in HEK293-D1R membranes, which increases dopamine affinity by approximately 7-fold and inhibits [³H]-SCH23390 binding by about 66% at 50 µM^[1].
MLS6585 (0.1-100 µM; 90 min) is a positive allosteric modulator of dopamine-stimulated β-arrestin recruitment in CHO-K1 D1R cells, enhancing dopamine potency by approximately 7-8 fold and displaying low micromolar affinity (K_b 5.4 µM)^[1].
MLS6585 (50 µM) enhances dopamine-induced D1R internalization in U2OS cells, increasing dopamine potency by 6-fold without increasing maximal internalization^[1].
MLS6585 increases DA affinity at D1R in radioligand binding assays^[4].