Biological activity of drug accessories.

News EventS July 25 in the journal Science published a study of academic and industrial collaboration (J. Pottel et al., "The Activities of the drug inactive ingredients on biological targets." Science, 369:403-13, 2020.), measures the biological activity of common drug accessories.
the authors selected 639 chemicals considered bio-inert inthetaous from the FDA's inert component salinns list and used computational methods to predict the interaction with 3,117 fully identified protein targets.
selected 69 pairs from possible 20,000 pairs of interactions for experimental verification, and resulted in at least 19 accessories with at least one target having a binding force.
the authors also measured the combination of 73 of the most commonly used excipients and 28 common toxic targets, resulting in 32 accessories combined with at least one target, of course, the two sets of problem accessories have a fairly cross.
although most of these substances are not combined with these targets in patients with sufficient concentrations in the use of doses, there are two accessories that have a greater biological effect.
FDA said it would not comment on the findings, while manufacturers said they would study them carefully to ensure safety. Professor Brian Shoichet, one of the communication authors of the
Drug Source Analysis, is a well-known computational chemist, but is very fond of asking some of the most basic questions of pharmaceutical chemistry.
more than a decade ago he discovered that the so-called frequent frequent drug screening senomer is often caused by the formation of physical polymers that denature the protein, because the concentration sized by these substances can form these microparticles under common screening conditions, and if the protein concentration is reduced, the activity disappears.
such a precursor clearly could not be optimized into a drug, and the concept became the basis of painS.
to verify the versatility of FBDD, he gradually cut a highly active protein substrate into a reduced-active fragment, and then crystallized each intermediate with the protein to obtain some column crystal structure.
found that each intermediate is different from the protein binding pattern, such a target if forward from the fragment to optimize according to the FBDD principle obviously will not be very high success rate, some success stories are only survivor bias, can not be used as evidence of the superiority of a model.
he has also studied the biological mechanisms of common weird quantitative curves.
today's study is also a common sense that everyone turns a blind eye and is self-evident, and while most accessories prove to be safer, we do need such rigorous scientific data.
finished medicine not only has active substances (APIs) but also need a variety of accessories to improve stability, solubility, strange taste and so on.
many accessories are components in food or have many years of experience in use, so they are considered safe.
but considering that some accessories (such as cyclodextrin derivatives) are much more complex than the molecular structure of some drugs (such as metformin), it is not surprising to have binding force with certain biological macromolecules.
fortunately, most of the existing accessories from this study to see the safety is basically no problem, which is of course a good thing.
but this work is only a part of measuring protein targets, there are many not fully identified proteins, so may miss some interaction, I know that FDA-approved auxiliary acid is nM level GPR35 agonis.
in addition to proteins and nucleic acids and other biological macromolecules may cause toxic side effects, so this study is only at a certain level to let everyone eat a basic accessories of the heart-based pills.
because there are a lot of unknowns in the whole drug discovery, so a lot of times there will be a situation of mindless insertion.
especially early new drug development is mainly through the overall animal experiment siftlet changes to screen drugs, accessories and impurities are sometimes real lying substances.
such as the anti-epileptic heavy-duty drug sodium valproate was supposed to dissolve the active substance as a solvent at the time, and later found that the solvent was the real active substance.
cyclodextrin is a common lysate (Redsewe needs a large amount of cyclodextrin to dissolve), and in previous years it has been found that some of the animal activity of steroid hormones actually comes from the dissolved cyclodextrin.
impurities eventually become more common in drugs, such as the asthma-old drug sodium cysonucleotide is a synthetic impurity.
of course, there are other misbehaving events related to our lack of knowledge, such as the current BIG Red Purple BTK inhibitor, which was used only as a tool to screen for compound activity, and later became a super-heavy drug.
the world of new drugs is complex, trust but verify.
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