Taminadenant (NIR178; PBF509) is a highly potent and orally active adenosine A 2A receptor (A 2A R) antagonist. Taminadenant can antagonize A2AR agonist-mediated cAMP accumulation and impedance responses with K B values of 72.8 nM and 8.2 nM, respectively. Taminadenant reverses motor impairments in several rat models of movement disorders, including catalepsy, tremor, and hemiparkinsonism. Taminadenant can also inhibit tumor growth when combined with Spartalizumab ( HY-P9972 ). Taminadenant reactivate the antitumor immune response
In Vitro
Taminadenant (PBF509) does not show any agonist efficacy in HEK cells permanently expressing the human A 2A R SNAP , but completely antagonizes the agonist-mediated cAMP accumulation in A 2A R SNAP expressing HEK cells with an IC 50 of 72.8 ± 17.4 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Taminadenant (PBF509) (0.3, 3, 7.5, 10, or 30 mg/kg; p.o.; single dosage) attenuates the cataleptic effects of Haloperidol, attenuates pilocarpine-induced tremulous jaw movement, enhances the effects of L-DOPA, shows a robust antiparkinsonian activity and displays antidyskinetic efficacy . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Sprague-Dawley rats (240-250 g; induced catalepsy by s.c. with 1 mg/kg Haloperidol (HY-14538)) Dosage: 3, 10, or 30 mg/kg Administration: p.o.; single dosage Result: Dose-dependently attenuated the cataleptic effects of Haloperidol when administered 1 h after Haloperidol injection. Animal Model: Sprague-Dawley rats (240-250 g; induced tremulous jaw movement by s.c. with 1 mg/kg Pilocarpine (HY-B0726A)) Dosage: 0.3, 3, or 7.5 mg/kg Administration: p.o.; single dosage Result: Dose-dependently attenuated pilocarpine-induced tremulous jaw movement, being effective at the lowest dose tested. Animal Model: Sprague-Dawley rats (240-250 g; induced hemiparkinsonian by unilateral injection of 6-OHDA (HY-B1081) in the medial forebrain bundle) Dosage: 0.3 and 3 mg/kg Administration: p.o.; single dosage Result: Enhanced the effects of L-DOPA with a minimum efficacious dose (MED) of 3 mg/kg p.o.. Animal Model: Sprague-Dawley rats (240-250 g; induced dyskinesias by i.p. 4 mg/kg L-DOPA (HY-N0304) for 14 days and i.p. 15 mg/kg Benserazide hydrochloride (HY-B0404A)) Dosage: 0.3 or 3 mg/kg Administration: p.o.; single dosage Result: Showed a robust antiparkinsonian activity and displayed antidyskinetic efficacy.
