API's patented and proprietary technology has proven successful in the discovery of new drug candidates also known as New Chemical Entities (NCEs). API has also partnered with other companies to develop NCEs in several drug classes. Based upon recently published validation and benchmark studies using proprietary search engines coupled with the results of searching stereochemically accurate databases, API is now providing drug discovery services.

API has constructed a wide variety of databases classified by drug type which are available for licensing. The databases contain stereochemically accurate structures critical in drug discovery. Such databases include classes of drugs and analogs specific for each pharmacophore and search engine (See lists below). The databases can be used in modeling studies and are searchable using API's NCE Search Engines. To our knowledge three dimensional stereochemically accurate databases of small molecules are not generally available in the public domain.

API has created a variety of search engines also available for licensing. The search engines can be used to automatically search 3D structural databases resulting in the identification of candidate biologically active compounds including potential NCEs. In addition to identifying new drug candidates among the search engine hits, the structures of the hits and the manner in which they fit the search criteria can be viewed interactively. This procedure provides a powerful tool to modify and redesign existing compounds thereby resulting in improved activity. It also provides a rational method to identify likely active compounds for inclusion in patents and intellectual property portfolios. APIs search engines include:

• Estrogen
• Antiestrogen
• Antiangiogenic
• Androgen
• SERM (Osteoporosis)
• Thyroid
• Sedative
• Oral Antidiabetic
• Retinoid
• Antidepressant
• Antipsychotic
• Glucocorticoid
• Antibiotic (Doxycycline/Ciprofloxacin)
• Mineralocorticoid
• Impotence
• Carcinogenic (Arene Oxide)

Multiple search engines can be employed simultaneously to search the same database or library of compounds. The results of these searches provide a means to determine whether a given molecule or set of molecules will have multiple biological activities. In this manner, the hit results can be used to improve the specificity of a given compound and/or detect potential untoward effects of a drug candidate e.g. certain "side effects" or toxicity. Conversely, the multiple search engines can identify potentially valuable, yet previously undetected activities of drug candidates thus providing potentially new uses for an existing drug or drug candidate.

Multiple search engines can also be used a priori to determine the likely profile of activities within a group of drug candidates and NCEs prior to biological testing. Such information is valuable for example when selecting which structures to synthesize including which templates to take forward to combinatorial chemistry and high throughput screening. In such cases, only those structures selected by multiple search engines to fit a desired drug activity profile would be chosen for further consideration resulting in savings of valuable time and development costs. Taken as a whole, this technology provides to our knowledge the only comprehensive in silico methodology to identify NCEs.

API has structures available for licensing which were designed using the technology. These structure are candidate NCEs for subsequent synthesis, analog development and biological testing.

API has a wide range of pharmacophores developed using its patented and proprietary technology. The pharmacophores are available for licensing and are cognate with the search engines and provide a visual tool to design new active compounds and redesign existing compounds. API also has pharmacophores which can assist in reducing certain untoward activities or "side effects". The following pharmacophores* are available:

• Estrogens
• Antiestrogens
• Androgens
• Antiandrogens
• Progestins
• Antiprogestins
• Glucocorticoids
• Antiglucocorticoids
• Mineralocorticoids
• Antimineralocorticoids
• Thyroid Drugs
• Retinoid Drugs
• Vitamin D Drugs
• Oral Antidiabetic Drugs
• Angiogenesis Drugs
• Antiangiogenesis Drugs
• Antimalarials
• COX Inhibitors
• Hepatoxicity
• Lipid Lowering Drugs

*Please note that some activities have multiple pharmacophores.

API has a scientific team with broad expertise in de novo drug design for a wide range of biological targets. In this regard, other companies can contract with API to build custom search engines and cognate pharmacophores to identify new lead compounds. In cases where a client has existing databases, API can provide search results to identify potential NCEs. Alternatively in cases where 3D databases are not available, API will provide contract services to create stereochemically accurate libraries of compounds as well as provide results of searching these databases. API can also use the search engines to assist a client in the evaluation of compounds present in existing, competing or pending patents as well as facilitate the expansion of patent claims and intellectual property portfolios.

Additional information about API's technology can be found under Validation & Benchmarks. A CD containing recent presentations of the technology, sample databases and interactive movies of the search engines can be obtained upon request (Contact Us).