Abstract
G-protein-coupled receptors (GPCRs) have been tractable drug targets for decades with over one-third of currently marketed drugs targeting GPCRs. Of these, the class A GPCR superfamily is highly represented, and continued drug discovery for this family of receptors may provide novel therapeutics for a vast range of diseases. GPCR allosteric modulation is an innovative targeting approach that broadens the available small molecule toolbox and is proving to be a viable drug discovery strategy, as evidenced by recent FDA approvals and clinical trials. Numerous class A GPCR allosteric modulators have been discovered recently, and emerging trends such as the availability of GPCR crystal structures, diverse functional assays, and structure-based computational approaches are improving optimization and development. This Perspective provides an update on allosterically targeted class A GPCRs and their disease indications and the medicinal chemistry approaches toward novel allosteric modulators and highlights emerging trends and opportunities in the field.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 88-127 |
| Number of pages | 40 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 62 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 1 2019 |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
Allosteric Modulation of Class A GPCRs : Targets, Agents, and Emerging Concepts. / Wold, Eric A.; Chen, Jianping; Cunningham, Kathryn; Zhou, Jia.
In: Journal of Medicinal Chemistry, Vol. 62, No. 1, 01.10.2019, p. 88-127.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Allosteric Modulation of Class A GPCRs
T2 - Targets, Agents, and Emerging Concepts
AU - Wold, Eric A.
AU - Chen, Jianping
AU - Cunningham, Kathryn
AU - Zhou, Jia
PY - 2019/10/1
Y1 - 2019/10/1
N2 - G-protein-coupled receptors (GPCRs) have been tractable drug targets for decades with over one-third of currently marketed drugs targeting GPCRs. Of these, the class A GPCR superfamily is highly represented, and continued drug discovery for this family of receptors may provide novel therapeutics for a vast range of diseases. GPCR allosteric modulation is an innovative targeting approach that broadens the available small molecule toolbox and is proving to be a viable drug discovery strategy, as evidenced by recent FDA approvals and clinical trials. Numerous class A GPCR allosteric modulators have been discovered recently, and emerging trends such as the availability of GPCR crystal structures, diverse functional assays, and structure-based computational approaches are improving optimization and development. This Perspective provides an update on allosterically targeted class A GPCRs and their disease indications and the medicinal chemistry approaches toward novel allosteric modulators and highlights emerging trends and opportunities in the field.
AB - G-protein-coupled receptors (GPCRs) have been tractable drug targets for decades with over one-third of currently marketed drugs targeting GPCRs. Of these, the class A GPCR superfamily is highly represented, and continued drug discovery for this family of receptors may provide novel therapeutics for a vast range of diseases. GPCR allosteric modulation is an innovative targeting approach that broadens the available small molecule toolbox and is proving to be a viable drug discovery strategy, as evidenced by recent FDA approvals and clinical trials. Numerous class A GPCR allosteric modulators have been discovered recently, and emerging trends such as the availability of GPCR crystal structures, diverse functional assays, and structure-based computational approaches are improving optimization and development. This Perspective provides an update on allosterically targeted class A GPCRs and their disease indications and the medicinal chemistry approaches toward novel allosteric modulators and highlights emerging trends and opportunities in the field.
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U2 - 10.1021/acs.jmedchem.8b00875
DO - 10.1021/acs.jmedchem.8b00875
M3 - Article
VL - 62
SP - 88
EP - 127
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 1
ER -