I came across a term "millamolecule" to represent macrocycles with a molecular weight between 500 and 1,000 daltons. Google Scholar show several resources which use this term e.g., Google Scholar Results

What could be origin of this term or is it just a buzzword invented by pharma companies?


In their 2013 Annual Report titled Evolving to a Specialty Care Biopharma Company, a well-known pharmaceutical company, Bristol-Myers Squibb has introduced the following statement under the title, Developing Innovative Drug Platforms:

As R&D evolves its focus, it is also investing in technology platforms that concentrate on new ways to affect disease targets, including antibody drug conjugates, which combine the targeted benefits of biologics with the cancer-killing ability of traditional small-molecule chemotherapies. R&D also will further expand the potential use of millamolecules, which are larger than small molecules but smaller than biologics. These millamolecules may be able to better exploit novel targets and mechanisms by retaining the desirable properties of small molecules with the high degree of selectivity, especially against antigens, that biologics and small molecules have had difficulty targeting.

And then, Bristol-Myers Squibb Company has filled a patent under World Intellectual Property Organization (WIPO) claiming Pet-imaging immunomodulators, abstract of which states that:

The invention relates to the synthesis and use of $\ce{^{18}F}$-labeled millamolecules for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.

Thus, to my understanding, millamolecules is the word invented by Bristol-Myers Squibb Company's scientists to describe special set of molecules with different activity other than those exhibited by small molecules and higher polypeptides.

Finally, Medicinal & Pharmaceutical Chemistry glossary & taxonomy describes it as:

Millamolecules: Mid-range compounds that fall in size between small molecules and biologics. Size is not the only consideration for this class, as millamolecules should also be orally available and able to interrupt protein-protein interactions.

Unsurprisingly, their reference has also directed to Bristol Myers Squibb: Areas of Focus.

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    $\begingroup$ Thanks for the references. You are right that BMS must have introduced this term, but I am wondering what does milla- mean? Is it from mill- for thousand? $\endgroup$
    – M. Farooq
    Dec 15 '19 at 4:40
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    $\begingroup$ Okay, found a footnote in paper by BMS _it is just a buzz word. Editors should discourage buzzwords until and unless authors provide an etymology. This will be good for the long term history. The footnote "Bristol-Myers Squibb refers to cyclic and acyclic compounds with a molecular weight between 600 and 6000 Da as millamolecules. Millamolecules, especially macrocyclic millamolecules, are ideal for pursuing the so-called “undruggable targets” such as complex protein−protein interactions." ncbi.nlm.nih.gov/pmc/articles/PMC4499820 $\endgroup$
    – M. Farooq
    Dec 15 '19 at 6:18
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    $\begingroup$ You can see the problem right away with buzzwords. The BMS paper suggests a range of 600 to 6000 Da. In the original post, another reference said 500-1000 Da. Big difference! $\endgroup$
    – M. Farooq
    Dec 15 '19 at 6:23
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    $\begingroup$ It looks like the term was exposed at least three years earlier in 2010 BMS report. As for the name, I like to think it comes from the German Latin-based name Milla meaning "industrious", but it's a pure speculation on my side. $\endgroup$
    – andselisk
    Dec 15 '19 at 10:36
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    $\begingroup$ Someone in Germany also wondered "Explanation: Das scheint ein von BMS erfundener Begriff zu sein, er taucht praktisch nur in Zusammenhang mit dieser Firma auf. Ich würde ihn daher wörtlich übernehmen." proz.com/kudoz/english-to-german/medical-general/… $\endgroup$
    – M. Farooq
    Dec 15 '19 at 14:34

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