800+ billion ready-to-synthesize virtual compounds for bRo5 drug discovery

ChemInfinita is a steadily expanding make‑on‑demand virtual space built, in collaboration with Alipheron, from commercial and proprietary building blocks and lab‑validated reaction templates—designed to prioritize robust synthetic feasibility at scale.

The space is searchable through Alipheron’s Hyperspace Search and Pharos‑3D platforms, enabling rapid virtual exploration and practical search‑to‑synthesis workflows.

A defining feature is its deliberate emphasis on beyond‑Rule‑of‑5 (bRo5) chemical matter-an increasingly important region of chemical space for discovery programs aimed at “difficult” targets and non‑classical binding sites.

• Size: 800+ billion virtual compounds (first release)
• Design principle: synthesis‑aware enumeration from validated transformations
• Synthetic feasibility (typical range): ~55–85% (dependent on target chemistry and project timelines; quoted per project)
• Expected delivery (make/ship): 5–8 weeks for typical orders (project‑dependent)

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Why bRo5 matters now

Drug discovery has steadily moved beyond classical Rule‑of‑5 (Ro5) small molecules—especially when programs require ligands that can span larger, more complex interaction surfaces or engage binding sites that are shallow, extended, or discontinuous.

• Target fit: bRo5 compounds can be advantageous for targets with complex hot spots and multi‑point recognition, where added size and functional complexity can translate into improved binding solutions.
• Not a dead end for developability: modern bRo5 design leverages property balancing and concepts such as chameleonicity to make oral exposure and permeability attainable in carefully designed series.
• Practical implication: bRo5 is not simply “bigger molecules”—it is a distinct design regime that benefits from libraries built intentionally for it, rather than retrofitting Ro5‑biased collections.

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What makes ChemInfinita different

1) Ultra‑large scale plus synthesis‑aware construction

Many virtual spaces maximize size; fewer maintain a credible path to synthesis at meaningful scale. ChemInfinita combines ultra‑large size with a reaction‑first, feasibility‑anchored build philosophy.

2) bRo5‑forward by design

ChemInfinita prioritizes regions that are often harder to cover with general‑purpose spaces—especially bRo5‑relevant chemotypes (e.g., macrocycle‑like and conformationally adaptive architectures, and other high‑information‑content scaffolds).

3) Built for modern discovery workflows

Large spaces only matter if teams can search them, prioritize them, and translate them into synthesis plans. ChemInfinita is designed to plug into today’s computational pipelines—from similarity and substructure search to structure‑based triage and AI‑assisted prioritization.

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How ChemInfinita fits into drug‑discovery pipelines

Hit discovery

• Rapid hypothesis generation for “difficult” targets where conventional Ro5 libraries underperform
• Expansion around early hits into bRo5‑adjacent neighborhoods while maintaining synthetic realism

Hit‑to‑lead

• Series expansion designed to explore potency/selectivity trade‑offs across larger binding surfaces
• Property‑aware prioritization strategies consistent with published bRo5 guidance (e.g., permeability/solubility/PSA trade‑offs; chameleonicity concepts)

Partnering modes

• Make‑on‑demand synthesis from shortlisted virtual hits (route feasibility anchored to validated transformations)
• Custom subspace builds around your target class, binding hypothesis, or property envelope

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What you can request

Depending on your workflow—and together with Alipheron - we can provide:

• Space access package (Pharos‑3D and Hyperspace Search)
• Targeted subsets (e.g., bRo5‑enriched subsets; project‑defined chemical boundaries)
• Synthesis‑ready hit lists (with practical ordering and handoff to synthesis)

Deliverable formats are tailored to the platform used by your team.

Update cadence: typically, biannual space updates (with optional intermediate updates).

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FAQ

Is the full 800+B list available as a single file?

Typically not. At this scale, ChemInfinita is intended to be explored via search and prioritized export (subsets, hits, focused neighborhoods), aligned with compute and storage constraints.

How should we think about “synthetic feasibility” (55–85%)?

This reflects real‑world variance: feasibility depends on the specific transformation class, chosen synthons, target functional constraints, and acceptable timelines. We treat feasibility as a project parameter, not a marketing number.

What types of targets benefit most?

Programs involving extended interfaces, hot‑spot complexity, and non‑classical binding topologies are common bRo5 beneficiaries.

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ChemInfinita vs. typical virtual spaces

A factual, non‑competitive comparison panel.

Dimension	ChemInfinita™	Typical virtual spaces
Primary design goal	Synthesis‑aware exploration at ultra‑large scale, with an emphasis on practical follow‑up synthesis	Often optimized for scale, novelty, or search coverage, with feasibility handled downstream
Build inputs	Combines commercial + proprietary building blocks with lab‑validated reaction templates	Often based primarily on public/commercial building‑block catalogs and/or broadly defined reaction rules
Chemical emphasis	Deliberately bRo5‑forward (beyond‑Rule‑of‑5 chemical matter is a major design target)	Frequently Ro5‑leaning by default; bRo5 coverage varies widely by provider
“Makeability” assumptions	Feasibility is explicitly encoded through chosen transformations and building‑block curation; typically communicated as a practical range	Feasibility may be implicit (post‑filtered) or treated as an optional add‑on
How users typically consume it	Designed for search → prioritize → export subsets/hits, rather than moving the full enumerated set around	Ranges from downloadable enumerations to search‑only platforms, depending on provider
Update cadence	Periodic, controlled releases (e.g., biannual updates; optional interim updates by need)	Updates range from continuous refresh to infrequent releases, often not standardized
Best‑fit use cases	Programs needing bRo5 chemical matter, challenging targets, and realistic synthesis follow‑up	Broad general screening, rapid idea generation, or exploratory searches across wide chemical space
What to ask any provider (good practice)	Reaction definitions, building‑block provenance, ID stability, feasibility metrics, export formats, and update policy	Same questions apply—answers vary by platform and curation philosophy

 

Ordering / inquiries: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 

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Key references

• Egbert, M., Whitty, A., Keserű, G. M., & Vajda, S. (2019). Why some targets benefit from beyond rule of five drugs. Journal of Medicinal Chemistry, 62(22), 10005–10025. https://doi.org/10.1021/acs.jmedchem.8b01732
• Caron, G., Kihlberg, J., Goetz, G., Ratkova, E., Poongavanam, V., & Ermondi, G. (2021). Steering new drug discovery campaigns: Permeability, solubility, and physicochemical properties in the bRo5 chemical space. ACS Medicinal Chemistry Letters, 12(1), 13–23. https://doi.org/10.1021/acsmedchemlett.0c00581
• García Jiménez, D., Vallaro, M., Vitagliano, L., Lopez Lopez, L., Apprato, G., Ermondi, G., & Caron, G. (2024). Molecular properties, including chameleonicity, as essential tools for designing the next generation of oral beyond rule of five drugs. ADMET and DMPK, 12(5), 721–736. https://doi.org/10.5599/admet.2334
• Sadybekov, A. V., & Katritch, V. (2023). Computational approaches streamlining drug discovery. Nature, 616, 673–685. https://doi.org/10.1038/s41586-023-05905-z