Technology
The pillars of LCGC Technology are:
- Intelligent compound-pooling for abbreviated HTS or combinatorial drug discovery
- Automated storage and retrieval to preserve quality of chemical assets and support SAR modeling
- Innovative open innovation framework for public-private partnering
- Diverse, proprietary chemical assets for high-throughput drug discovery
Combinatorial Screening Technology
The orthogonal-pooled screening (OPS) technology is an abbreviated, highly efficient HTS paradigm that enables five-fold improvement in lead-finding efficiency with 80 percent cost reduction. It guarantees lower costs and enhanced data quality for large-scale screening enterprises and can greatly expand ability for smaller labs to discover novel drug leads. Peer-reviewed publications strongly validate that—when properly applied—OPS works as good or better than classical HTS. Our unique compound collections (> 150,000 unique small molecules) were orthogonally 10-pooled with best practices in computational chemistry and automated compound-management operations. We make this proprietary asset available to drug-screening scientists as a research service at very reasonable cost.
How this research service works:
- We provide the assay-ready compound-dotted plates, e.g., 8,000 compounds in duplicate in only five 384-well plates (Pilot OPS); we work with you to ensure successful outcomes.
- You run the assay in the plates and send us the reader data.
- We de-convolute the data to reveal orthogonal hits.
- We deliver a structure-activity report of hits.
- We then ship hits at 10X the original screening concentration, enough sample for confirmation of activity and specificity.
- We resupply confirmed hits as neat powders for determining mechanism of action.
- Option for similarity searching and supply from our own of commercial catalogs.
- Turnaround time is three to four days for data analysis and cherry-picking.
Our version of OPS is unprecedented. We offer it as a turnkey HTS-support service, including access to our rare compound libraries and a full complement of hit-to-lead follow-on support. We guarantee OPS will work for your target assay, or there is no charge.
Please see our Combinatorial Screening Overview (PDF)
Contact us directly to understand how we can apply our technologies in non-obvious ways to benchmark, and then measurably and quickly enhance quality of data throughout your organization. Melvin Reichman 484.476.8230 or [email protected].
NARS Technology
We have developed a powerful, self-contained, fully automated repository robot called the NanoTube Automated Repository System (NARS) that has dynamic storage capacity of 10 million samples. Completely enclosed in a -20°C dehumidified environment, a cherry-picking robot provides up to 10,000 samples per day throughput. The NARS stores replicates of single-shot aliquots in small, individually addressable storage containers holding sealed chemical or biological samples. The NARS provides unparalleled, high throughput storage, retrieval and distribution for large chemical collections, without any freeze-thawing, thereby preserving the integrity of the entire collection indefinitely. There is no better, more cost-effective approach for core compound management required for successful leads discovery. Our NARS services offer:
- Outsourced management of compound collections for very reasonable service fees
- Proper storage and high-throughput retrieval of large chemical and biological collections, protecting them from damaging freeze-thaw cycles
- Biorepository applications for siRNA, genomic DNA, biological or sensitive natural products collections
- Just-in-time hit2lead support with powerful QC/QA for all HTS operations
Double-Blinded Drug Discovery (DBD2®)
Only a fraction of cellular proteins in the druggable genome has been exploited medicinally. Hundreds of promising—but immature (i.e., medicinal potential not yet translated)—targets are under intense investigation by university scientists. Many are orphan proteins whose roles yet remain to be fully resolved. Thus, a large part of the proteome remains open to potential medicinal exploitation, including targets like transcription factors, protein-protein interactions and misfolded protein targets prone to pathogenic aggregation. Even the largest pharma company cannot afford to internally prosecute the druggability of more than a small handful of immature targets.
Also, many compelling target programs have not borne fruitful outcomes, despite immense effort by many pharmas at prodigious costs. A new drug discovery approach seems desirable for avoiding the costs and risks of premature commitment to nascent targets.
Better prioritization for hypothesis-stage targets is a critical impact opportunity for pharmas to sustain a more fruitful pipeline of first-in-class medicines, thereby avoiding drug-pipeline development gaps leading to painful patent cliffs.
The terms of the DBD2 Collaborative Agreement (DCA) reflect endorsements from many universities and pharmas. The DCA ensures fair use of individually owned intellectual property and safeguards against the premature escape of sensitive structure-activity data. It is particularly suitable in public-private research collaborations between university and company scientists for exploring the medicinal potential of novel cell-signaling targets. Both companies and institutions benefit from option rights to further develop new IP jointly or independently. The inherent efficiencies of DCA allow pursuit of more projects in parallel, while avoiding administrative encumberment that has long stymied advancing discovery-research collaborations between industrial and university investigators.
DBD2®:
- Offers unprecedented research services to the corporate R&D enterprise at very low cost
- Expands core chemical genomics capabilities for university participants at no cost
- Accelerates technology transfer and commercialization without compromising sensitive IP
- Offers a new way to validate druggable targets and chemotypes, potentially including synergistic combination drugs
View our Double-Blinded Drug Discovery overview (PDF)
References
- Reichman M, Simpson PB. Open innovation in early drug discovery: roadmaps and roadblocks. Drug Discov Today. 2016 May;21(5):779-88. doi: 10.1016/j.drudis.2015.12.008. Epub 2015 Dec 29. Review. PubMed PMID: 26743597
- Simpson PB, Reichman M. Opening the lead generation toolbox. Nat Rev Drug Discov. 2014 Jan;13(1):3-4. doi: 10.1038/nrd4202. PubMed PMID: 24378783
- Donover PS, Yohn M, Sim M, Wright A, Gowda S, Allee C, Schabdach AR, Reichman M. New informatics and automated infrastructure to accelerate new leads discovery by high throughput screening (HTS). Comb Chem High Throughput Screen. 2013;16:180-8. PMID: 22934945
Unique Chemical Libraries
LIMR owns a unique compound library of 104,000 members, with powder reserves of 10 mg each. This was once the research asset of a major company that donated the resource to LIMR for the greater good. The structures were designed with a cheminformatic perspective that differs from more common approaches. These compounds pass Lipinski and drug reactivity filters typically used in pharma to qualify drug-like libraries for high throughput screening and feasibility as medicines. Creation of customized focused libraries is easily accomplished for thousands of compounds in days, rather than weeks.