Advancing Cancer Drug Development: A 2025 Snapshot of the Small-Molecule Oncology Drug Pipeline

While checkpoint-blocking antibodies continue to dominate clinical headlines, a new generation of immuno oncology drugs in development are small molecules designed to modulate innate and adaptive immunity with oral or intratumoral dosing:

These approaches underscore an ongoing shift in immuno oncology drug discovery toward chemical matter that can be combined with antibodies, antibody-drug conjugates, or radioligands for synergistic efficacy.

Modern anti cancer drug design leverages high-resolution structural biology, AI-enabled property prediction, and in-silico ADME-Tox modeling to compress timelines in the development of anticancer drugs:

• Screening of millions of compounds – DEL screening allows for the identification of high-affinity compounds from a single round of screening. Visit our services here.
  
  
• Structure-Guided Modeling – Cryo-EM structures of e.g. KRAS and RAF complexes have guided ras targeted drug development to picomolar affinity. Generative AI – Transformer-based models propose synthetically tractable scaffolds for “difficult” pockets (e.g. β-catenin) within days.
  
  
• Covalent fragment growing – Used to create first-in-class covalent KRAS (G12C) inhibitors, demonstrating the power of anti cancer drug discovery that combines warhead chemistry with macromolecular insight.
  
  
• Macrocycle Design – Enables oral inhibition of allosteric mutant p53 re-activators, expanding the druggable proteome.

Collectively, these tools accelerate cancer drug design and discovery from hit identification to IND in <24 months—a milestone once reserved for antivirals.

KRAS (G12C) – Prototype for undruggable success 

• Sotorasib gained global approval for the treatment of non-small-cell lung cancer (NSCLC) in 2021.
• Adagrasib secured accelerated FDA approval and is under study in colorectal cancer (CRC).

Tissue-Agnostic Therapies 

• The approval of Larotrectinib for NTRK-fusion tumors illustrates tissue agnostic drug development in oncology.

Hematologic Malignancies 

• Venetoclax (BCL-2 inhibitor) transformed therapy for both Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML) drugs in development
• Ivosidenib (IDH1 inhibitor) exemplifies targeted therapy in AML and cholangiocarcinoma

DEL Screening marries combinatorial chemistry with next-generation sequencing (NGS), enabling the interrogation hundreds of millions of unique compounds in a single experiment. Key benefits for cancer target discovery and development include:

• Speed – hit emerge in weeks, shrinking the early cancer drug discovery research timeline.
• Novel chemotypes – DEL campaigns routinely identify scaffolds absent from commercial collections.
• Diverse targets – successful against E3 ligases (PROTAC starting points), kinases, proteases, epigenetic readers and more all enriching the new cancer drug discovery toolkit.

Read more about Vipergen’s DNA Encoded Libraries and Screening.