LY-2456302

• CAT Number: I007802
• CAS Number: 1174130-61-0
• Molecular Formula: C26H27FN2O2
• Molecular Weight: 418.5124
• Purity: ≥95%
• Synonyms: LY-2456302; LY 2456302; LY2456302; JSPA0658; CERC-501; CERC 501; CERC501.;Benzamide, 4-(4-(((2S)-2-(3,5-dimethylphenyl)-1-pyrrolidinyl)methyl)phenoxy)-3-fluoro-
• Target: κ-opioid receptor Antagonist
• Solubility: Soluble in DMSO
• Storage: 0 - 4°C for short term , or -20°C for long term.
• InChI: InChI=1S/C26H27FN2O2/c1-17-12-18(2)14-21(13-17)24-4-3-11-29(24)16-19-5-8-22(9-6-19)31-25-10-7-20(26(28)30)15-23(25)27/h5-10,12-15,24H,3-4,11,16H2,1-2H3,(H2,28,30)/t24-/m0/s1
• InChIKey: ZHPMYDSXGRRERG-DEOSSOPVSA-N
• SMILES: O=C(N)C1=CC=C(OC2=CC=C(CN3[C@H](C4=CC(C)=CC(C)=C4)CCC3)C=C2)C(F)=C1

LY-2456302 (CAST: I007802), also known as CERC-501, is a potent and selective antagonist of the κ-opioid receptor. The κ-opioid receptor is a type of opioid receptor found in the central nervous system and plays a role in modulating pain perception, stress responses, and mood regulation. LY-2456302 acts by blocking the activity of the κ-opioid receptor, which can have therapeutic implications in the treatment of various conditions such as depression, anxiety, and substance abuse disorders. As a short-acting antagonist, LY-2456302 has the advantage of rapid onset and clearance, making it suitable for certain clinical applications.

Reference

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
Z(1).

Author information:
(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.