Advancing Biochemical Molecule Registration, Representation and Search for New Drug Modalities.

Area of Science:

• Drug discovery and development
• Cheminformatics and computational chemistry
• Biotechnology and pharmaceutical sciences

Background:

• The pharmaceutical industry is rapidly adopting novel drug modalities beyond traditional small molecules.
• Existing cheminformatics infrastructure, optimized for small molecules, is inadequate for representing the complexity of new modalities like peptides, oligonucleotides, and ADCs.
• Current standards, such as the Hybrid Electronic/Oligonucleotide/Peptide/RNA (HELM) notation, exhibit limitations in capturing the full structural and chemical diversity of these advanced therapeutics.

Purpose of the Study:

• To identify and analyze the cheminformatics challenges associated with representing and managing data for next-generation therapeutics, including therapeutic peptides, modified oligonucleotides, and antibody-drug conjugates (ADCs).
• To evaluate the limitations of current data representation standards and infrastructure in handling the structural complexity of these new drug modalities.
• To propose a path forward for developing robust, standardized, and interoperable chemical information systems essential for advancing therapeutic innovation.

Main Methods:

• Analysis of cheminformatics infrastructure gaps based on practical experience within the pharmaceutical industry (AstraZeneca).
• Examination of the technical constraints of current representation methods (e.g., atomistic, sequence-based, HELM) when applied to peptides, oligonucleotides, and ADCs.
• Assessment of organizational challenges, including standardization, governance, and the impact of localized solutions.

Main Results:

• New drug modalities present significant challenges that exceed the capabilities of current atomistic or sequence-based cheminformatics representations.
• Existing standards like HELM have limitations in fully capturing the structural and chemical intricacies of peptides, oligonucleotides, and ADCs.
• Organizational issues, such as a lack of unified standards and effective governance, further contribute to data fragmentation and hinder interoperability.

Conclusions:

• Addressing the cheminformatics deficit for next-generation therapeutics requires moving beyond fragmented, local solutions.
• The development and adoption of vendor- and community-driven standards, coupled with open implementations and robust governance, are crucial.
• Establishing standardized and interoperable chemical information systems is imperative to support the continued innovation and development of advanced therapeutics.