New small-molecule drug design strategies for fighting resistant influenza A

Proteins of B-cell lymphoma (Bcl-2) family are key regulators of apoptosis and are involved in the pathogenesis of various cancers. Disrupting the interactions between the antiapoptotic and proapoptotic Bcl-2 members is an attractive strategy to reactivate the apoptosis of cancer cells. Structure-based drug design (SBDD) has been successfully applied to the discovery of small molecule inhibitors targeting Bcl-2 proteins in past decades. Up to now, many Bcl-2 inhibitors with different paralogue selectivity profiles have been developed and some were used in clinical trials. This review focused on the recent applications of SBDD strategies in the development of small molecule inhibitors targeting Bcl-2 family proteins.

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Solution Structure of a 2:1 Quindoline–c-MYC G-Quadruplex: Insights into G-Quadruplex-Interactive Small Molecule Drug Design

Journal of the American Chemical Society ◽

10.1021/ja205646q ◽

2011 ◽

Vol 133 (44) ◽

pp. 17673-17680 ◽

Cited By ~ 210

Author(s):

Jixun Dai ◽

Megan Carver ◽

Laurence H. Hurley ◽

Danzhou Yang

Keyword(s):

Drug Design ◽

Small Molecule ◽

Solution Structure ◽

Small Molecule Drug ◽

G Quadruplex

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Strategies to identify ligands for orphan G-protein-coupled receptors

Biochemical Society Transactions ◽

10.1042/bst0300789 ◽

2002 ◽

Vol 30 (4) ◽

pp. 789-793 ◽

Cited By ~ 20

Author(s):

G. Milligan

Keyword(s):

Drug Design ◽

G Protein ◽

Small Molecule ◽

Drug Targets ◽

G Protein Coupled Receptors ◽

Orphan Receptors ◽

Protein Targets ◽

Small Molecule Drug ◽

Natural Ligands ◽

G Protein Coupled

G-protein-coupled receptors are the most tractable class of protein targets for small molecule drug design. Sequencing of the human genome allied to bio-informatic analysis has identified a large number of putative receptors for which the natural ligands remain undefined. A range of currently employed and developing strategies to identify ligands that interact with these orphan receptors and to validate them as drug targets are described and discussed.

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Small molecule drug conjugates (SMDCs): an emerging strategy for anticancer drug design and discovery

New Journal of Chemistry ◽

10.1039/d0nj04134c ◽

2021 ◽

Vol 45 (12) ◽

pp. 5291-5321

Author(s):

Tarun Kumar Patel ◽

Nilanjan Adhikari ◽

Sk. Abdul Amin ◽

Swati Biswas ◽

Tarun Jha ◽

...

Keyword(s):

Drug Design ◽

Anticancer Drug ◽

Small Molecule ◽

Chemotherapeutic Agents ◽

Drug Molecule ◽

Lysosomal Ph ◽

Small Molecule Drug ◽

Drug Conjugates ◽

Small Molecule Drugs ◽

Tumor Environment

Mechanisms of how SMDCs work. Small molecule drugs are conjugated with the targeted ligand using pH sensitive linkers which allow the drug molecule to get released at lower lysosomal pH. It helps to accumulate the chemotherapeutic agents to be localized in the tumor environment upon cleaving of the pH-labile bonds.

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