Design and Synthesis of Cannabinoid 1 Receptor (CB1R) Allosteric Modulators: Drug Discovery Applications

2017 ◽  
pp. 281-315 ◽  
Author(s):  
Abhijit R. Kulkarni ◽  
Sumanta Garai ◽  
David R. Janero ◽  
Ganesh A. Thakur
Keyword(s):  
Drug Discovery ◽  
Allosteric Modulators ◽  
Design And Synthesis ◽  
Cannabinoid 1 Receptor

Design and synthesis of mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease

2021 ◽  
pp. 113646
Author(s):  
Iván Beltran-Hortelano ◽  
Richard L. Atherton ◽  
Mercedes Rubio-Hernández ◽  
Julen Sanz-Serrano ◽  
Verónica Alcolea ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Mannich Base ◽  
Design And Synthesis ◽  
Lead Compounds

scholarly journals Design and Synthesis of Inhibitors ofPlasmodium falciparumN-Myristoyltransferase, A Promising Target for Antimalarial Drug Discovery

2012 ◽  
Vol 55 (20) ◽  
pp. 8879-8890 ◽  
Author(s):  
Zhiyong Yu ◽  
James A. Brannigan ◽  
David K. Moss ◽  
A. Marek Brzozowski ◽  
Anthony J. Wilkinson ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Antimalarial Drug ◽  
Design And Synthesis ◽  
Promising Target

Design and Synthesis of a (N-Alkylaminoalkyl-Substituted)Arylalkenylamide Drug Discovery Library

2007 ◽  
Vol 4 (8) ◽  
pp. 605-610 ◽  
Author(s):  
M. Urbano ◽  
S. Collina ◽  
D. Rossi ◽  
A. Baraglia ◽  
S. Alcaro ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Design And Synthesis

scholarly journals Allosteric Modulators for GPCRs as a Therapeutic Alternative with High Potential in Drug Discovery

2020 ◽  
Author(s):  
Arfaxad Reyes-Alcaraz ◽  
Emilio Y. Lucero Garcia-Rojas ◽  
Richard A. Bond ◽  
Bradley K. McConnell
Keyword(s):  
Drug Discovery ◽  
Signaling Pathways ◽  
Therapeutic Benefit ◽  
High Potential ◽  
Screening Methods ◽  
Allosteric Modulators ◽  
Endogenous Ligand ◽  
New Findings ◽  
Multiple Signaling ◽  
G Protein Coupled

The superfamily of G protein-coupled receptors (GPCRs) consists of biological microprocessors that can activate multiple signaling pathways. Most GPCRs have an orthosteric pocket where the endogenous ligand(s) typically binds. Conversely, allosteric ligands bind to GPCRs at sites that are distinct from the orthosteric binding region and they modulate the response elicited by the endogenous ligand. Allosteric ligands can also switch the response of a GPCR after ligand binding to a unique signaling pathway, these ligands are termed biased allosteric modulators. Thus, the development of allosteric ligands opens new and multiple ways in which the signaling pathways of GPCRs can be manipulated for potential therapeutic benefit. Furthermore, the mechanisms by which allosteric ligands modulate the effects of endogenous ligands have provided new insights into the interactions between allosteric ligands and GPCRs. These new findings have a high potential to improve drug discovery and development and, therefore, creating the need for better screening methods for allosteric drugs to increase the chances of success in the development of allosteric modulators as lead clinical compounds.

scholarly journals Rational Design and Synthesis of Novel Dual Protacs for Simultaneous Degradation of EGFR and PARP

2021 ◽  
Author(s):  
Mengzhu Zheng ◽  
Junfeng Huo ◽  
Xiaoxia Gu ◽  
Canrong Wu ◽  
Qingzhe Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Drug Discovery ◽  
Rational Design ◽  
Bispecific Antibodies ◽  
Design And Synthesis ◽  
Synthetic Strategy ◽  
Dual Targeting ◽  
Different Types ◽  
Natural Amino Acids ◽  
Simultaneous Degradation

Inspired by the success of dual targeting drugs, especially bispecific antibodies, we propose to combine the concept of protac and dual targeting to design and synthesize dual protac molecules with the function of degrading two completely different types of targets simultaneously. A library of novel dual targeting protac molecules have been rationally designed and prepared. A convergent synthetic strategy has been utilized to achieve high synthetic efficiency. These dual protac structures are characterized by using trifunctional natural amino acids as star-type core linkers to connect two independent inhibitors and E3 ligands together. In this study, gefitinib, olaparib, and CRBN or VHL E3 ligand were used as substrates to synthesize novel dual protacs. They successfully degraded both EGFR and PARP simultaneously in cancer cells. Being the first successful example of dual protacs, this technique will greatly widen the range of application of the protac method and open up a new field for drug discovery.

Design and Synthesis of γ- and δ-Lactam M1 Positive Allosteric Modulators (PAMs): Convulsion and Cholinergic Toxicity of an M1-Selective PAM with Weak Agonist Activity

2017 ◽  
Vol 60 (15) ◽  
pp. 6649-6663 ◽  
Author(s):  
Jennifer E. Davoren ◽  
Michelle Garnsey ◽  
Betty Pettersen ◽  
Michael A. Brodney ◽  
Jeremy R. Edgerton ◽  
...  
Keyword(s):  
Allosteric Modulators ◽  
Agonist Activity ◽  
Design And Synthesis ◽  
Positive Allosteric Modulators
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