Heteromer Induction: An Approach to Unique Pharmacology?

Philip S. Portoghese; Eyup Akgün; Mary M Lunzer

doi:10.1021/acschemneuro.7b00002

Heteromer Induction: An Approach to Unique Pharmacology?

Philip S. Portoghese, Eyup Akgün, Mary M Lunzer

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

It is proposed that two types of opioid receptor heteromers exist: a) those that are constitutive and b) those that are induced by bivalent ligands. Mu opioid agonists interact with constitutive MOR-DOR heteromer to mediate tolerance and dependence. Bivalent ligand, MDAN21, is devoid of these adverse effects by virtue of its DOR antagonist pharmacophore. We propose that bivalent ligands MMG22 and MCC22 induce colocalized receptors to form heteromers (MOR-mGluR5 and MOR-CCR5, respectively) that do not occur naturally, thereby promoting unique pharmacology. Heteromer induction with bivalent ligands offers a general approach to unique pharmacology that complements traditional SAR.

Original language	English (US)
Pages (from-to)	426-428
Number of pages	3
Journal	ACS Chemical Neuroscience
Volume	8
Issue number	3
DOIs	https://doi.org/10.1021/acschemneuro.7b00002
State	Published - Mar 15 2017

Bibliographical note

Funding Information:
This research was supported by NIH Grant R01 DA030316.

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

DOR
MOR
heterodimer
opiod receptor

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Heteromer Induction: An Approach to Unique Pharmacology?",

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Heteromer Induction: An Approach to Unique Pharmacology?

Abstract

Bibliographical note

Keywords

UN SDGs

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