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In molecular biology and pharmacology, a small molecule is a low molecular weight (< 900 daltons) organic compound that may help regulate a biological process, with a size on the order of 1 nm. Most drugs are small molecules.
The upper molecular-weight limit for a small molecule is approximately 900 daltons, which allows for the possibility to rapidly diffuse across cell membranes so that they can reach intracellular sites of action. In addition, this molecular weight cutoff is a necessary but insufficient condition for oral bioavailability. Finally, a lower molecular weight cutoff of 500 daltons (as part of the "rule of five") has been recommended for small molecule drug development candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this 500 dalton limit.
Most pharmaceuticals are small molecules.
From: https://en.wikipedia.org/wiki/Small_molecule
For the period 2009–2011. Chart from: August 2012 ,Vol. 4, No. 12, Pages 1527-1531 , DOI 10.4155/fmc.12.94 (doi:10.4155/fmc.12.94)
Target - cel, w domyśle biological target czyli cel biologiczny. Makromolekuła, najczęściej białko, z którym oddziałuje lek (najczęściej mała molekuła) w efekcie czego obserwujemy pożądany efekt biologiczny (a w efekcie np wyzdrowienie pacjenta).
- Targets of FDA approved drugs (source: doi:10.1038/nrd2199)
- Pathogen and human: 324
- Human: 266
- Small-molecule drugs
- pathogen and human: 248
- Human: 207
(Hint: the total number of proteins in human cells is estimated to be between 250,000 to one million. source: proteomics.cancer.gov)
- Marketed small-molecule drug targets by biochemical class (source: doi:10.1038/nrd892)
- enzymy: 47%
- GPCRy: 30%
- kanały jonowe: 7%
- inne
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IC50 - half maximal inhibitory concentration wiki
- pIC50 = -log(IC50)
- EC50 - half maximal effective concentration
- LD50 - median lethal dose
- Ki - binding affinity - describes the interaction of most ligands with their binding sites; high-affinity ligand binding results from greater intermolecular force between the ligand and its receptor while low-affinity ligand binding involves less intermolecular force between the ligand and its receptor. In general, high-affinity binding involves a longer residence time for the ligand at its receptor binding site than is the case for low-affinity binding.
The median affinity (IC50, EC50, ED50, Ki, Kd) for current small-molecule drugs is around 20 nM (source: doi:10.1038/nrd2199)
ADMET – akronim odzwierciedlający w skrócie losy leku w ustroju, po jego podaniu. Nazwa pochodzi od pierwszych liter angielskich nazw głównych procesów, które zachodzą od momentu podania leku do jego wydalenia:
- A – absorption (wchłanianie)
- D – distribution (rozmieszczenie)
- M – metabolism (metabolizm)
- E – excretion (wydalanie)
- T - toxicity (toksyczność)