The PAP consists of two main research components:

• Discovery and development of new chemical entities and their mixtures for human therapeutic uses.
• Ethnobotanical lead collection, study, prioritization and development.

The Plant Associate Program (PAP) for the first time, is exposing Western science to the

chemodiversity of the Central Asian flora and comprehensively exploring this chemodiversity for new botanical therapeutics. In today's $300 billion global pharmaceutical market, approximately 25% of all prescriptions contain active agents originally derived from plants. Nevertheless, only a small fraction of the 250,000 known plant species have been fully analyzed for potential human health benefits. Due to their geographic location and climatic and topographical diversity, Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan and Kyrgyzstan contain widely diverse, largely unexplored and species-rich floras adapted to deserts, steppes, forests and some of the world's highest mountains and characterized by high level of endemism. It is estimated that the four partnering countries have approximately 7,000 native plant species growing in their territories. The Associated Programs operating in Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan produced plant extracts used by the program. These programs are be closely integrated with the PAP.

SCREENING

These research objectives are being investigated using several approaches, such as 1) Real Time RT-PCR screening of plant and fungal extracts; 2) partial sample de-replication, isolation and characterization of actives and comprehensive investigation of their interactions (performed in conjunction with the Structural and Analytical Chemistry Associate Program) 3) cell culture-based production of difficult to re-supply phytochemicals; and 4) value-added agriculture. Real Time RT-PCR screening simultaneously quantify the expression of key genes involved in targeted human diseases such as cancer, obesity/diabetes, auto-immune/inflammatory diseases and mental disorders. These screens are used for the PAP and the Fungal Associate Program.

SAMPLING

While one of the purposes of the plant sample collection is the comprehensive sampling of plant biodiversity of Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan, some emphasis is being placed on sampling endemic plants and plants that either belong to families known for high natural product production or are known as local medicinal plants. In addition, plant collecting Associate Programs in Kazakhstan, Kyrgyzstan, Tajikistan and Uzbekistan collected the same species from various extreme environmental conditions under the premise that plants exposed to different stresses often contain different inducible natural products with different bioactivities. All collected samples are vouchered as herbarium specimens. Samples are prepared by extracting plant shoots, roots and reproductive structures in 80% methanol. Active compounds from the most active samples, which have passed primary and secondary screens and the dereplication process, are isolated and structurally characterized at University of Illinois with assistance from Rutgers University. The ethnobotanical lead collection part of the program already generated over 20 relatively advanced leads.

IMPACT

PAP, working in close association with the partnering countries, 1) promotes pharmaceutical discovery, 2) facilitates the development of country-relevant botanical therapeutics, 3) contributes to capacity and infrastructure improvements, 5) stimulates the development of natural product-based health industry and 6) supports increased biodiversity conservation in Central Asia.