Design, Synthesis and Evaluation of Novel Inhibitors Toward Targeted Therapy

Dear Colleagues,

The rapid evolution of precision medicine has reshaped our understanding of how chemical agents can be tailored to modulate specific molecular drivers of disease. As biological pathways grow increasingly complex and previously “undruggable” proteins emerge as high-value targets, the need for innovative small-molecule inhibitors—supported by rigorous design principles and mechanistic insight—has never been greater. Advances in synthetic chemistry, structural analysis, computational modeling, and biological profiling are jointly enabling inhibitors with unprecedented selectivity, potency, and translational potential.

This Special Issue aims to showcase state-of-the-art research and critical perspectives in the design, synthesis, and evaluation of novel inhibitors for targeted therapy, and assemble a collection of high-impact studies that advance the conceptual, methodological, and translational framework of targeted inhibitor development. This topic stands at a pivotal intersection of chemistry and biology, with significant implications for therapeutic innovation across multiple disease landscapes. Aligned with the scope of the journal, we seek contributions that integrate fundamental chemical principles with biological application—ranging from mechanistic elucidation to preclinical therapeutic exploration.

In this Special Issue, both original research articles and reviews are welcome. Research areas may include, but are not limited to, the following topics:

• High-throughput screening-driven drug discovery towards undruggable targets;
• Rational design and synthesis of novel inhibitors targeting disease-relevant proteins;
• Mechanistic studies elucidating inhibitor–target interactions;
• Development and application of bifunctional modalities (e.g., PROTACs, molecular glues, PhosTACs, RiboTACs, DUBTACs);
• Structure–activity relationships (SAR) and pharmacophore modeling;
• Chemical biology probes for functional interrogation of signaling pathways;
• Computational and AI-driven strategies supporting inhibitor discovery;
• Inhibitors targeting transcription factors, epigenetic regulators, kinases, and protein complexes;
• Preclinical evaluation, cellular assays, selectivity profiling, and therapeutic validation;
• Novel synthetic methodologies enabling new chemical space for targeted therapeutics;
• Integrative approaches combining chemistry, omics technologies, and structural biology.

We look forward to receiving your contributions. 

Dr. Elisa Nuti
Guest Editor

Dr. Bocheng Wu
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the Special Issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.