Purity: > 98%
LY-2456302(cas 1174130-61-0), also known as CERC-501, is a potent, selective, short-acting antagonist of the κ-opioid receptor (KOR) (Ki = 0.81 nM vs. 24.0 nM and 155 nM for the μ-opioid receptor (MOR) and δ-opioid receptor (DOR). LY-2456302 is under development for the treatment of major depressive disorder and substance use disorders including alcoholism, nicotine addiction, and illicit drug dependence. LY-2456302 has been found to dose-dependently block fentanyl-induced miosis at 25 mg and 60 mg in humans (with minimal to no blockade at doses of 4 to 10 mg), indicating that the drug significantly occupies and antagonizes the MOR at a dose of at least 25 mg but not of 10 mg or less.
1. Transl Perioper Pain Med. 2016;1(2):4-16.
Major Depressive Disorder and Kappa Opioid Receptor Antagonists.
Li W(1), Sun H(1), Chen H(1), Yang X(1), Xiao L(1), Liu R(2), Shao L(1), Qiu
(1)Department of Medicinal Chemistry, School of Pharmacy, Fudan University.
(2)Department of Anesthesiology and Critical Care, Perelman School of Medicine,
University of Pennsylvania.
Major depressive disorder (MDD) is a common psychiatric disease worldwide. The
clinical use of tricyclic antidepressants (TCAs), monoamine oxidase inhibitors
(MAOIs) and selective serotonin reuptake inhibitors
(SSRIs)/serotonin-norepinephrine reuptake inhibitor (SNRIs) for this condition
have been widely accepted, but they were challenged by unacceptable side-effects,
potential drug-drug interactions (DDIs) or slow onset/lack of efficacy. The
endogenous opioid system is involved in stress and emotion regulatory processes
and its role in MDD has been implicated. Although several KOR antagonists
including JDTic and PF-04455242 were discontinued in early clinical trials, ALKS
5461 and CERC-501(LY-2456302) survived and entered into Phase-III and Phase-II
trials, respectively. Considering the efficacy and safety of early off-label use
of buprenorphine in the management of the treatment-resistant depression (TRD),
it will be not surprising to predict the potential success of ALKS 5461 (a
combination of buprenorphine and ALKS-33) in the near future. Moreover, CERC-501
will be expected to be available as monotherapy or adjuvant therapy with other
first-line antidepressants in the treatment of TRD, if ongoing clinical trials
continue to provide positive benefit-risk profiles. Emerging new researches might
bring more drug candidates targeting the endogenous opioid system to clinical
trials to address current challenges in MDD treatment in clinical practice.