CERC-501
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Systematic (IUPAC) name | |
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4-(4-{[(2S)-2-(3,5-Dimethylphenyl)-1-pyrrolidinyl]methyl}phenoxy)-3-fluorobenzamide
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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 |
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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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