ReviewCurrent topics in medicinal chemistry2018
Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.
Review in Current topics in medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
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- Identification and characterization of a novel inhibitor of influenza A virus that acts by blocking nucleoprotein oligomerization.Antimicrobial agents and chemotherapy · 2026Article
- The Malaria Box molecules: a source for targeting the RBD and NTD cryptic pocket of the spike glycoprotein in SARS-CoV-2.Journal of molecular modeling · 2024Article
- Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.Journal of cellular and molecular medicine · 2024Article
- Development of SARS-CoV-2 entry antivirals.Cell insight · 2024Review
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- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
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- Broad-Spectrum Small-Molecule Inhibitors of the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction from a Chemical Space of Privileged Protein Binders.Pharmaceuticals (Basel, Switzerland) · 2022Article
- CEBIT screening for inhibitors of the interaction between SARS-CoV-2 spike and ACE2.Fundamental research · 2022Article
- Methylene Blue Is a Nonspecific Protein-Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19.Pharmaceuticals (Basel, Switzerland) · 2022Article
- tRNAAntimicrobial agents and chemotherapy · 2022Article
- Development of Low-Molecular-Weight Compounds Targeting the Cancer-Associated KLF5 Transcription Factor.ACS medicinal chemistry letters · 2022Article
- Computational Simulations Highlight the IL2Rα Binding Potential of Polyphenol Stilbenes from Fenugreek.Molecules (Basel, Switzerland) · 2022Article
- Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Protein-Protein Interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/ manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.