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

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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Holistic Drug Design for Multiparameter Optimization in Modern Small Molecule Drug Discovery

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2021.128003 ◽

2021 ◽

pp. 128003

Author(s):

Lewis D. Pennington ◽

Ingo Muegge

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Small Molecule ◽

Small Molecule Drug ◽

Multiparameter Optimization

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Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-17-3457 ◽

2018 ◽

Vol 24 (15) ◽

pp. 3656-3667 ◽

Cited By ~ 31

Author(s):

Samuele Cazzamalli ◽

Barbara Ziffels ◽

Fontaine Widmayer ◽

Patrizia Murer ◽

Giovanni Pellegrini ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Small Molecule ◽

Interleukin 2 ◽

Carbonic Anhydrase Ix ◽

Therapeutic Activity ◽

Small Molecule Drug ◽

Drug Conjugates

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Fragment-based drug design of nature-inspired compounds

Physical Sciences Reviews ◽

10.1515/psr-2018-0110 ◽

2019 ◽

Vol 4 (9) ◽

Cited By ~ 1

Author(s):

Abdulkarim Najjar ◽

Abdurrahman Olğaç ◽

Fidele Ntie-Kang ◽

Wolfgang Sippl

Keyword(s):

Drug Design ◽

Small Molecules ◽

Small Molecule ◽

Binding Pocket ◽

Biological Macromolecules ◽

Drug Candidates ◽

Fragment Screening ◽

Small Molecule Drugs ◽

Lead Generation ◽

Hit Identification

Abstract Natural product (NP)-derived drugs can be extracts, biological macromolecules, or purified small molecule substances. Small molecule drugs can be originally purified from NPs, can represent semisynthetic molecules, natural fragments containing small molecules, or are fully synthetic molecules that mimic natural compounds. New semisynthetic NP-like drugs are entering the pharmaceutical market almost every year and reveal growing interests in the application of fragment-based approaches for NPs. Thus, several NP databases were constructed to be implemented in the fragment-based drug design (FBDD) workflows. FBDD has been established previously as an approach for hit identification and lead generation. Several biophysical and computational methods are used for fragment screening to identify potential hits. Once the fragments within the binding pocket of the protein are identified, they can be grown, linked, or merged to design more active compounds. This work discusses applications of NPs and NP scaffolds to FBDD. Moreover, it briefly reviews NP databases containing fragments and reports on case studies where the approach has been successfully applied for the design of antimalarial and anticancer drug candidates.

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