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Contributor Drug Discovery Insights

Alfred Ajami

I have managed pharmaceutical and biomedical research enterprises for over forty years, creating patented innovations in chemical biology. My research and expertise are in the fields of medicinal chemistry and all aspects of pre-clinical drug development, with a heavy emphasis on phenotypic studies and physiologically based PK/PD. I was trained both as a biologist and a chemist. In 2013, I left the executive rat race in the Kendall Square pharma Mecca (Cambridge, MA). Now, when not consulting to early stage companies or running portfolio reviews and due diligence, I spend my time analyzing and commenting on trends.

 

Assay Technology Big Data Biologics Biopharma Policies, Regulations CRISPR Database Drug Targets High-Throughput Screening (HTS) Immunotherapy In Silico MedChem Small Molecules

Posts by this author

Converging Trends Brings Organic Electrochemistry To The Front Line Of Drug Discovery

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Converging Trends Brings Organic Electrochemistry To The Front Line Of Drug Discovery

In a case of "back to the future", chemists at Scripps collaborating with instrument engineers at IKA have unveiled a powerful tool for electrifying chemistry to achieve complex reactions. The ElectraSyn is expected to change approaches to 3D-molecules, late-stage derivatization, and focused library construction, while promoting environmentally conscious chemistry. The teaser graphic here is from Ref. 5 in the text that follows.

How To Hunt For Drugs In Dark Chemical Matter

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Pharma productivity has remained a daunting challenge, notably because R&D departments have been shuffled and reorganized over the last few years in attempts to revitalize the process. One trend, among multiple parallel tracks, has come into fashion. With millions of compounds in inventory, why not re-examine the ones that have consistently shown no activity in bioassays (and presumed are safe if inactive also in toxicological assays) rather than re-invent new ones? Enter the concept of exploring Dark Chemical Matter (DCM).

How CRISPR Transforms Modern Drug Discovery

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Consensus seems universal and the news about it flows literally by the minute over gene editing as a future therapy, complete with patent sagas and ethical conundrums. But at the bench, CRISPR's impact is also proving disruptive, and revolutionary, soon to irrevocably change the mechanics of drug discovery and pre-clinical development in multiple ways. One particular set of  CRISPR applications should be on every drug hunter's radar: disease relevant cellular reporter models manipulated to reflect disease phenotypes.

How Many Drug Targets Are There? A Status Update Review

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The question is often raised, but the answer remains to be uncovered because the definition of drug "target" continues to evolve.  Historical conceptualization is focused on catalytic sites, substrate binding sites, or epigenetic modification sites. Current understanding that protein-protein interactions are druggable, along with the emerging realization that "nodes" in signaling pathways and biological networks themselves can be manipulated with small molecules in non-traditional ways, has opened up new targeting options. This review is intended to provide a status update, and you can also access a list of 36 actionable web resources for target hunting.

36 Web Resources For Target Hunting In Drug Discovery

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Choosing the right biological target or a combination of targets is a fundamental task for any successful drug discovery project. All the subsequent efforts -- be it a small molecule hit identification, lead optimization, pharmacokinetic studies, or a clinical trial -- will just be as effective, at the end of the day, as was the initial decision to choose one target or another.

The Homunculus Metaphor Revisited In Drug Discovery: Body-on-a-Chip

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The Homunculus Metaphor Revisited In Drug Discovery: Body-on-a-Chip

The16th century alchemical and 19th century science fiction revival of a miniature human being in a test tube is undergoing a radical upgrade. Microfluidics,  complex organoid cultures, and nanodetection of phenotypic and genomic outputs are turning the metaphor into a reality to be seriously reckoned with in drug R&D. Here are recent highlights from the (mostly) open access literature, which should bring drug hunters up to speed

Three Insights For Immuno-oncology Drug Discovery

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Immunotherapies are hot property. Immuno-oncology is the crown jewel. But the road to riches, and more importantly cancer cures, is now crowded and full of potholes. Drug hunters need to look ahead, beyond the discovery process itself, to the reality of the many impediments that will confront drug candidates as they proceed towards the clinic in today's landscape. Here, I present three insights from current events, the third one taking a contrarian position.

A Brief Guide To Assay Technology For Efficient Drug Discovery -- Part 1

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Effective drug discovery begins with the right assay, but the definition of "right" will shift as technology advances. More often than not, "right" is the product of tribal knowledge, namely the traditions of one's close peer group, study lineage and corporate culture. Instead, the right assay should be a fit-for-purpose application born of  a broader, continuously updated, and unbiased consensus. As Steve Hamilton, aka The Lab Man, at the Society for Laboratory Automation  and Screening (SLAS) has often stated in his blog posts, "developing assays – properly – is the cornerstone for life sciences R&D."