The LIMR Chemical Genomics Center (LCGC) offers unprecedented services for pharmaceutical R&D to scientists in industry and academia.
- Unique—not available elsewhere
- Bridges gaps that have stymied academia-pharma collaborations for advancing medicinal research in areas of urgent patient need
Orthogonal Pooled Screening (OPS) is a combinatorial-HTS strategy that enables the rapid screening of large compound libraries against multiple targets. Mixtures of 10-pooled compounds are screened instead of individual compounds. Each compound is in two locations in the mixture plates, mixed with a different set of nine other compounds in each location. Thus, hits are imputed by the correlated activities of a compound in two locations. Orthogonal pooling of 100 compound plates yields 20 mixture plates; reagent costs and screening times are thereby reduced significantly. An extensive list of references on OPS in peer-reviewed publications is included in the OPS Tutorial. We make this service available with two options.
a) Pilot OPS Option: “Self Deconvoluting Mini-Libraries” of 8,000 compounds from our unique chemical collection, with structural diversity not available elsewhere. Compounds on sets of five plates are provided as orthogonal-pooled screening (OPS) arrays, comprised of intelligently mixed 10-pools in duplicate in 384-well assay-ready plates (16,000 data points from 8,000 compounds with only 1,600 tests). You simply run your assay in screening-ready plates and send us the plate-reader data. With three-day turnaround time, we compile a structure-activity relationship report and deliver cherry-picked samples for hit confirmation, pharmacological specificity and mechanism of action studies. Please download our OPS Tutorial for more detail.
b) Full OPS Option: Our entire 152,000 compound collection is made available to scientists in academia and industry for Ultra-HTS. LCGC delivers up to ninety-five (95) 384-well plates, containing 152,000 compounds—in duplicate. The service is an expansion of our Pilot OPS program, including providing cherry picks of DMSO stocks for confirming activity and specificity and revealing structure-activity relationships (SAR). Up to 10 mg of neat powders are available for the majority of our Core Collection. If you plan to run several screens per year, we offer a discounted subscription service with just-in-time support. A detailed description of our infrastructure and approach has been published (PMID: 22934945).
Automated research materials management
Our compound stock solutions in DMSO are maintained frozen in our NanoTube Automated Retrieval system (NARS)—a state-of-the-art, low-temperature robotic repository system of our own patented design that has been strongly validated. No freeze-thaw cycling preserves quality. The NARS also has DNA and other biorepository applications. Its capacity is 10-million individual samples and has high throughput cherry-pick capability. We can prepare focused or diversity libraries of a few dozen to tens of thousands of custom-picked compounds. The cost of our cherry-pick samples is 1/10th or less than the per sample price of commercial vendors. We also provide neat powders for more than 70,000 compounds; most of them are exclusive to LCGC.
Ultra-HTS for synergy (uHTSS)
This is a special approach for potentially enabling scientists to explore chemical and biological space in a new way to discover synergistic combinations. The foundation is our patented uHTSS method, having 15-fold greater efficiency than the classic serial-cross-dilution screening paradigm. This new combination-drug discovery technology potentially is a way to rescue terminated clinical candidates for the intended indication, or evaluate repurposed indications with a special approach we call synergistic drug repositioning. This innovative technology can also be applied for new product development in ChemAg, fragrance, medical food or dietary supplement, and flavor R&D segments. We welcome collaborations with academic or industrial scientists to apply this special technology, including via joint grant applications. Please contact us to discuss our novel combination-drug discovery concept for revealing mutually dependent cell-signaling pathways believed to coordinate pathogenesis in multi-factorial complex diseases. uHTSS is particularly applicable where single drugs are not known or approved drugs have insufficient efficacy, or lose their efficacy to drug resistance.
HTS quality benchmarking
We can measurably improve QC/QA in drug discovery with a unique benchmarking service for total quality management of discovery research operations. It is especially applicable in sponsored or CRO-outsourced drug discovery campaigns, where the wise will trust, but also validate performance. We lend the gamut of our state-of-the-art resources and considerable experience to guarantee measurable improvements in quality of data, including determining false ± hit-rates, and for comparing protocols in real time to select optimum screening conditions. Please contact us for more detail on this unprecedented discovery-research support service.