Small Molecules

Kristina Whitfield

May 22, 2017

Cell Culture

‘Small molecules’ (SMs) in life sciences research, usually mean a bioactive small molecules. While there isn’t necessarily anything that makes SMs research reagents especially distinct from pharmaceutical APIs, SMs production is typically cheaper than APIs. However, it is a problem for any supplier trying to gain a foothold in a niche and the best bet is to be armed with a good amount of comparative data combined with competitive pricing.

Author: Kristina Whitfield Undertakes marketing activities for Pivotal Scientific and their clients.

Kristina Whitfield

Introduction

‘Small molecules’ (SMs) are a diverse set of organic molecules that can be hard to pin down more specifically. In life sciences research, what we usually mean is bioactive small molecules, with a mass no more than about one kilodalton. Scientists can use these small molecules to activate or inhibit some biological function or property. The main targets for small molecules in research are enzymes (e.g. receptors, ion channels or kinases). Disrupting (or restoring) their normal function allows the part they play in health and disease processes to be revealed.

The majority of drugs are small molecules, a testament to their power in the biosciences. Although that is slowly changing with the relatively recent introduction of biologics in medicine. Thinking in terms of market for SMs, it’s worth noting that some care is needed in assessing the research market.

SMs research market

Generally, there isn’t necessarily anything that makes small molecule research reagents especially distinct from pharmaceutical ‘small molecule Active Pharmaceutical Ingredients’ (APIs), a related but different market. The distinctions between these two types are minimal in the majority of market reports. There are informations about small molecules use more commonly in research context compared to those in the drug development process. Moreover, one important distinction is that, generally speaking, API’s are produced to a more onerous set of specifications (i.e. GMP) than research small molecules due to their potential use in living subjects. This is something which can also affects costs. Meaning that, although, taking purity and similar characteristics into consideration, SMs production is typically cheaper than APIs.

While SMs can be classified based on their chemical nature, for research reagents that’s not so useful. Instead, it is better to think of small molecules based on their biological function or research area. For example as ‘inhibitors’ or ‘apoptosis and cell cycle reagents’, especially from a user and marketing perspective. Typically, suppliers of SMs tend to fall into one of two groups – those that fulfil specific niches which complement their other product portfolios, such as immunology or cell biology, and those who offer broad panels of SM products for testing in a customer’s application.

Over the last couple of decades, the use of small molecules in the biosciences has taken a bit of a back seat due to the rise of protein/antibody based technologies. However, producers of small molecules have not been idle. Larger and larger panels of SMs are being produced allowing researchers to screen hundreds or thousands of SMs in their assay systems for the ones which give the desired response, as well as large catalogues of SMs with known functionality against specific targets.

Potential problem

One problem when bringing a new SM entity to the market is overcoming user preference for older ‘tried and tested’ SMs for an application – even where they are demonstrably worse. Take, for example, dichlorofluorescein (DCFH), a fluorescent small molecule used as an indicator of oxidative stress. In some applications DCFH is known to lack selectivity or precipitate out in side reactions, affecting the reliability of results. However, some have highlighted that it’s use persists despite alternatives being available which solve these problems.

Convincing the research community of the benefits of new products, whether dyes, like DCFH, or kinase inhibitors is not a new problem in the industry. However, it is still a problem for any supplier trying to gain a foothold in a niche. In most cases the best bet is being armed with a good amount of comparative data demonstrating the benefits compared to the current industry standard (and if in published literature, all the better) combined with competitive pricing.

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