Analogue and Standalone Drugs

doi:10.1515/ci.2008.30.5.20

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Analogue and Standalone Drugs

Published/Copyright: September 1, 2009

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From the journal Chemistry International -- Newsmagazine for IUPAC Volume 30 Issue 5

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Analogue and Standalone Drugs

In the book Analogue-Based Drug Discovery, published by Wiley-VCH in 2006 under the aegis of IUPAC, we focused first of all on analogue drugs with a double similarity—that is, those that are similar to another drug from both chemical and pharmacological viewpoints. These were referred to as full analogues. The book also discussed some examples of structural analogues, which have similar chemical structures but different pharmacological properties. We also proposed using the term pharmacological analogues to describe drugs that have completely different chemical structures but similar pharmacological properties.

In 2006 a new project of IUPAC’s Division VII (Chemistry and Human Health) was started to study the role and the importance of standalone drugs; these are defined as drugs that are neither structural nor pharmacological analogues. The project is chaired by Janos Fischer (Richter Plc) with Robin Ganellin (University College London), Arun Ganesan (University of Southampton), and Dr. John Proudfoot (Boehringer Ingelheim, Ridgefield, United States) as project members.

In this preliminary report, we give a short overview of the top 100 most important drugs worldwide based on the sales data of IMS, a company that provides comparative sales data on the pharmaceutical industry. In 2006 the global sale of drugs amounted to USD 638 billion. The sales of the top 100 drugs represented about 51 percent of global sales (i.e., USD 326 billion). Table I shows that 84.4 percent of sales of the top 100 drugs derives from small molecule drugs, whereas macromolecular drugs and biological entities amount to 9.2 percent of sales and vitamins and a hormone amount to 6.4 percent of sales.

Table 1. Drugs Types of the Top 100 Drugs
Drug Types	Sales (2006) USD (billions)	Ratio (%)	Numbers
Small Molecule Drugs	275	84.4	80
Macromolecules and Biological Entities	30	9.2	10
Vitamins and Hormones	21	6.4	10

The importance of small molecule drugs remains very high in spite of the increasing role of macromolecular drugs (proteins) and biological entities (monoclonal antibodies).

Table 2 lists the small molecule drugs that are among the top 100 drugs according to their analogue status.

Table 2. Types of Small Molecule Drugs among the Top 100 Drugs
Small Molecule Drug Type	Number
Pioneer drugs	10
Full analogues	51
Pharmacological analogues	8
Structural analogues	2
Standalone drugs	9

It is remarkable how high the number (51) of full analogues is among the top 100 drugs. The analogue drugs among the top 100 belong to 42 different analogue classes of drug action, as defined by the main pharmacological effect (e.g., ACE inhibitors, α₁-blockers, AT₁ antagonists, β-lactamase inhibitors), and there are only 10 pioneer drugs (“first in class”) among the top 100 drugs from the analogue classes. This is because the pioneer drugs were improved through the making of analogues, and continuous optimization has produced additional analogue drugs that are even better.

The following nine standalone drugs have been identified from among the top 100 drugs: acetaminophen, acetylsalicylic acid, aripiprazole, bupropion, ezetimibe, lamotrigine, metformin, topiramate, and valproate semisodium.

In this project we are focusing on the role of standalone drugs. We will analyze their importance, the need for improvement, and the difficulties in their optimization. The older drugs, such as acetaminophen and acetylsalicylic acid, particularly merit optimization because of their serious side effects.

For more information and comments, contact János Fischer <j.fischer@richter.hu> or C. Robin Ganellin <c.r.ganellin@ucl.ac.uk>.

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Analogue and Standalone Drugs

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Published Online: 2009-09-01

Published in Print: 2008-09

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https://doi.org/10.1515/ci.2008.30.5.20