CERC-501

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CERC-501
LY-2456302.svg
Systematic (IUPAC) name
4-(4-{[(2S)-2-(3,5-Dimethylphenyl)-1-pyrrolidinyl]methyl}phenoxy)-3-fluorobenzamide
Clinical data
Routes of
administration
Oral
Pharmacokinetic data
Biological half-life 30–40 hours
Identifiers
CAS Number 1174130-61-0
ATC code None
PubChem CID: 44129648
ChemSpider 28424203
Chemical data
Formula C26H27FN2O2
Molecular mass 418.503 g/mol
  • CC1=CC(=CC(=C1)[C@@H]2CCCN2CC3=CC=C(C=C3)OC4=C(C=C(C=C4)C(=O)N)F)C
  • 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
  • Key:ZHPMYDSXGRRERG-DEOSSOPVSA-N

CERC-501 (originally known as LY-2456302) is a potent, selective, short-acting (non-"inactivating") 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), respectively; ~30-fold selectivity for the KOR) that was originally developed by Eli Lilly.[1][2][3] In February 2015, Cerecor Inc. announced that they had acquired the rights from Eli Lilly to develop and commercialize LY-2456302 (under the new developmental code name of CERC-501).[4]

CERC-501 is under development for the treatment of major depressive disorder and substance use disorders including alcoholism, nicotine addiction, and illicit drug dependence.[5] As of 2016, it has reached phase II clinical trials as an augmentation to antidepressant therapy for treatment-resistant depression.[6][7] In animal models of depression, CERC-501 has been found to have potent synergistic efficacy in combination with other antidepressants such as citalopram and imipramine.[7] A phase II study of CERC-501 in heavy smokers will be commenced in early 2016 and results of the study are expected before the end of 2016.[8]

In December 2015, the results of a human pharmacokinetic study of CERC-501 were released.[5][8] CERC-501 was shown to reproducibly penetrate the blood-brain-barrier, and positron emission tomography imaging revealed that brain KORs were almost completely saturated by the drug 2.5 hours following a single dose of 10 mg, which supported the 4 mg to 25 mg dosages that CERC-501 is being explored in clinical trials.[5][8] Occupancy was 35% for a 0.5 mg dose and 94% for a 10 mg dose.[8] At 24 hours post-dose, receptor occupancy was 19% for 0.5 mg and 82% for 25 mg.[8] No serious side effects were observed, and all side effects seen were mild to moderate and not considered to be due to CERC-501.[8]

CERC-501 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.[9]

See also

References

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External links


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