Finding Opportunities for a single advanced compound, or a chemotype of interest.

nPharmakon will identify previously unrecognized, therapeutically relevant molecular targets, suggest new therapeutic opportunities to the Customer.

Deliverables:
  • identity of therapeutically important new molecular targets; activities confirmed in vitro;
  • targets' roles in different pathologies, available pre-clinical and clinical validation;
  • potential novel indications supported by compounds' ADMET properties;
  • competition, including compounds in clinical development, and drugs approved by the FDA for the novel indications;
  • early chemical optimization strategy for addressing the new molecular target and indication.

Prioritizing Liabilities for a single development candidate, or a chemotype of interest.

nPharmakon will identify potential molecular targets linked to side effects or toxicities, enabling the Customer to efficiently review and prioritize potential liabilities, and order testing of the drug candidate(s) in the most appropriate in vitro / in vivo assays.

Deliverables:
  • identity of potential toxicity-related molecular targets;
  • toxicities expected to result from the modulation of the targets' activities in vivo;
  • availability of appropriate in vitro and in vivo assays.

Finding Drug-Like Small Molecule Leads, Tool Compounds For Protein Targets for a single target, several related targets, or a list of targets e.g. as generated by a functional screen.

For protein targets specified by the Customer, nPharmakon will find drug-like small molecule leads or tool compounds in one or more of the following compound collections: (1) nPharmakon's collection of molecules tested in animals; (2) nPharmakon's curated collection of investigational and approved drugs from around the world; (3) collection of drug-like molecules supplied by the Customer; (4) nPharmakon's collection of publicly known tool compounds.

The amenable targets include (1) targets with tool compounds, either known publicly or identified by the Customer; or (2) targets with small molecule binding sites that are structurally similar to those of proteins with known chemistry. 3D structure is not required.

Deliverables:
  • Feasibility assessment, determining which of the targets specified by the Customer can be addressed using nPharmakon's proprietary chemogenomics methods. Includes list of known tool compounds.
  • Optionally, nPharmakon can suggests additional druggable targets in the pathways of interest to be included in the analysis.
  • Prioritized list of candidate molecules predicted to be active against the specified target(s). Vendor(s) for the identified molecules. Vendor(s) for the screening assays.

Rescaffolding for a single compound, a chemotype, or a set of chemically unrelated molecules.

Starting with molecules (such as HTS hits or stalled development candidates) provided by the Customer, nPharmakon will identify for the Customer new molecules that

  • are likely, from the analysis of their 3D shape and other molecular properties, to have activity against the same target as the molecule(s) provided by Customer;
  • are lead-like or drug-like (and optionally, have been used in humans, i.e. are drugs already), and
  • have a different chemical scaffold than the Customer's molecule(s).

Benefits to the Customer: decrease the lead optimization effort, overcome patentability issues, synthesis or optimization difficulties, or persistent liabilities.

The Customer will be able to limit the new molecules to those available commercially, or to request synthetically accessible compounds, including novel compounds, regardless of their availability. To ensure lead-likeness or drug-likeness, nPharmakon will search in its collection of compounds tested in biological models, as collected from the public sources, and optionally in the collection of drugs assembled at nPharmakon, and use predictive methods.

Deliverables:
  • chemical molecules optimally satisfying the above properties;
  • where available, literature references and a summary of experimentally determined properties;
  • where available, vendors of the identified molecules.

nPharmakon will employ its proprietary chemogenomic methods and databases to help the Customer derive maximum value from a phenotypic screen, by designing a screening library optimally matched to the biology of the assay and "primed" for subsequent MOA deconvolution, and by designing optimal follow-on ("backscreen") library.

Benefits to the Customer: increase the likelihood of identifying relevant druggable targets; identify MOA of the actives and save time and money by optimizing against defined molecular targets.

Deliverables:
  • custom screening library, assembled from commercially available small molecule tool and drug-like compounds, designed so as to comprehensively probe the biology of the assay, identify novel targets, and test a broad range of mechanism-of-action (MOA) hypotheses;
  • testable MOA hypotheses for the active compounds;
  • backscreen library, assembled from commercially available drug-like compounds, compounds tested in biological models, and tool compounds known or predicted to be active against molecular targets implicated to play a role in the biological context addressed by the assay.

Size of the screening libraries can vary from about 100 to 10,000 compounds depending on assay throughput, according to the specifications provided by the Customer. MOA deconvolution and backscreen library design services can be performed using the data obtained with nPharmakon-designed as well as non-nPharmakon-designed screening libraries.

The compound library design and interpretation of the screening results may incorporate additional proprietary information available from Customer, e.g. results of an RNAi screen.