LY 2456302

Research use only, not for human use.

LY 2456302 (CERC-501, JSPA 0658, Aticaprant) is a potent, selective, short-acting antagonist of κ-opioid receptor (KOR) with Ki of 0.81 nM.

LY 2456302 (CERC-501, JSPA 0658, Aticaprant) is a potent, selective, short-acting antagonist of κ-opioid receptor (KOR) with Ki of 0.81 nM; displays >30-fold selectivity over MOR and DOR; selectively and potently occupies central kappa opioid receptors in vivo (ED50=0.33 mg/kg); produces antidepressant-like effects in the mouse forced swim test and enhanced the effects of imipramine and citalopram; orally-bioavailable and excellent pharmacokinetic properties.Depression Phase 2 Clinical.

Aticaprant (CERC-501) binds with high affinity to the human kappa opioid receptor with a 30-fold higher affinity over the human mu opioid receptor and 190-fold higher affinity over the human delta opioid receptor. Aticaprant (CERC-501) shows no appreciable affinity for several non-opioid cell surface G-protein-coupled receptor targets, including monoaminergic, muscarinic, cholinergic, and adrenergic receptors or ion channel/transporter binding targets or the central benzodiazepine binding site.

Aticaprant (CERC-501) has a rapid absorption (tmax=1-2 h) and good oral bioavailability (F=25%). Oral Aticaprant (CERC-501) administration selectively and potently occupies central kappa opioid receptors (ED50=0.33 mg/kg), without evidence of mu or delta receptor occupancy. LY2456302 potently blocks kappa-agonist-mediated analgesia and disruption of prepulse inhibition, without affecting mu-agonist-mediated effects at doses >30-fold higher. Aticaprant (CERC-501) produces antidepressant-like effects in the mouse forced swim test and enhances the effects of imipramine and citalopram. Aticaprant (CERC-501) reduces ethanol self-administration in alcohol-preferring rats. Aticaprant (CERC-501) alleviates the nicotine withdrawal syndrome, as evidenced by decreased expression of nicotine withdrawal induced anxiety-related behavior, somatic signs, and CPA, and increased hotplate latency in nicotine withdrawn mice following pre-treatment.

CERC-501 | JSPA 0658 | Aticaprant

Endocrinology/Hormones

Opioid Receptor

Opioid Receptor

Neurological Disease

Depression

1174130-61-0

418.512

C26H27FN2O2

>98% (HPLC)

DMSO : ≥ 100 mg/mL 238.95 mM

O=C(N)C1=CC=C(OC2=CC=C(CN3[C@H](C4=CC(C)=CC(C)=C4)CCC3)C=C2)C(F)=C1

4-(4-(((2S)-2-(3,5-dimethylphenyl)-1-pyrrolidinyl)methyl)phenoxy)-3-fluoro-benzamide

(-20℃)

With Ice Pack

≥ 2 years