210236-47-8Relevant academic research and scientific papers
Versatile Picklocks to Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe- d -Pro-Phe-Trp] (CJ-15,208)
De Marco, Rossella,Bedini, Andrea,Spampinato, Santi,Cavina, Lorenzo,Pirazzoli, Edoardo,Gentilucci, Luca
, p. 9255 - 9261 (2016)
Recently, the tryptophan-containing noncationizable opioid peptides emerged with atypical structure and unexpected in vivo activity. Herein, we describe analogs of the naturally occurring mixed κ/μ-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ-15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon enlarging macrocycle size, giving the μ-agonist 9 or the δ-antagonist 10 characterized by low nanomolar affinity. In particular, the μ-agonist c[β-Ala-d-Pro-Phe-Trp] 9 was shown to elicit potent antinociception in a mouse model of visceral pain upon systemic administration.
The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior
Aldrich, Jane V.,Senadheera, Sanjeewa N.,Ross, Nicolette C.,Ganno, Michelle L.,Eans, Shainnel O.,McLaughlin, Jay P.
, p. 433 - 438 (2013)
The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro- Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.
Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist
Ross, Nicolette C.,Kulkarni, Santosh S.,McLaughlin, Jay P.,Aldrich, Jane V.
supporting information; experimental part, p. 5020 - 5023 (2011/02/22)
The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.; Kojima, Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N. J. Antibiot. (
