AT-076

AT-076
Identifiers
  • (3R)-7-hydroxy-N-[(2S)-1-[4-(3-hydroxyphenyl)piperidin-1-yl]-3-methylbutan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC26H35N3O3
Molar mass437.584 g·mol−1
3D model (JSmol)
  • CC(C)[C@@H](CN1CCC(CC1)C2=CC(=CC=C2)O)NC(=O)[C@H]3CC4=C(CN3)C=C(C=C4)O
  • InChI=1S/C26H35N3O3/c1-17(2)25(16-29-10-8-18(9-11-29)19-4-3-5-22(30)12-19)28-26(32)24-14-20-6-7-23(31)13-21(20)15-27-24/h3-7,12-13,17-18,24-25,27,30-31H,8-11,14-16H2,1-2H3,(H,28,32)/t24-,25-/m1/s1
  • Key:LGYDWJJZDCXEOV-JWQCQUIFSA-N

AT-076 is a so-called opioid "pan" antagonist and is the first reasonably balanced antagonist known of all four opioid receptor types. It acts as an antagonist of all four types of opioid receptor, behaving as a competitive antagonist of the μ-opioid receptor (Ki = 1.67 nM) and δ-opioid receptor (Ki = 19.6 nM) and as a noncompetitive antagonist of the κ-opioid receptor (Ki = 1.14 nM) and nociceptin receptor (NOP, Ki = 1.75 nM). AT-076 was derived from the κ-opioid receptor antagonist JDTic, which showed affinity for NOP, by removal of two methyl groups from the piperidine ring. This increased affinity for NOP 10-fold relative to the parent compound.

See also

References

  1. 1 2 3 Zaveri NT, Journigan VB, Polgar WE (2015). "Discovery of the First Small-Molecule Opioid Pan Antagonist with Nanomolar Affinity at Mu, Delta, Kappa, and Nociceptin Opioid Receptors". ACS Chemical Neuroscience. 6 (4): 646–657. doi:10.1021/cn500367b. PMC 4401318. PMID 25635572.
  2. ↑ Munro TA, Huang XP, Inglese C, Perrone MG, Van't Veer A, Carroll FI, et al. (2013). Porter J (ed.). "Selective κ opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters". PLOS ONE. 8 (8) e70701. doi:10.1371/journal.pone.0070701. PMC 3747596. PMID 23976952.