Editing Small molecule (section)

== Molecular weight cutoff ==
The upper [[Molecular mass|molecular-weight]] limit for a small molecule is approximately 900 daltons, which allows for the possibility to rapidly diffuse across cell membranes so that it can reach [[intracellular]] sites of action.<ref name = "Dougherty_Pucci_2012"/><ref name="pmid12036371">{{cite journal |vauthors=Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD | title = Molecular properties that influence the oral bioavailability of drug candidates | journal = J. Med. Chem. | volume = 45 | issue = 12 | pages = 2615–23 |date=June 2002 | pmid = 12036371 | doi = 10.1021/jm020017n | citeseerx = 10.1.1.606.5270 }}</ref> This molecular weight cutoff is also a necessary but insufficient condition for oral [[bioavailability]] as it allows for [[transcellular transport]] through intestinal [[epithelial]] cells.  In addition to intestinal permeability, the molecule must also possess a reasonably rapid [[Dissolution (chemistry)#Rate of dissolution|rate of dissolution]] into water and adequate water [[solubility]] and moderate to low [[first pass metabolism]]. A somewhat lower molecular weight cutoff of 500 daltons (as part of the "[[rule of five]]") has been recommended for oral small molecule drug candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this limit.<ref>{{cite journal | author = Lipinski CA | title = Lead-and drug-like compounds: the rule-of-five revolution | journal = Drug Discovery Today: Technologies |date=December 2004 | volume = 1 | issue = 4 | pages = 337–341 | doi = 10.1016/j.ddtec.2004.11.007 | pmid = 24981612 }}</ref><ref name="pmid17971784">{{cite journal |vauthors=Leeson PD, Springthorpe B | title = The influence of drug-like concepts on decision-making in medicinal chemistry | journal = Nature Reviews Drug Discovery | volume = 6 | issue = 11 | pages = 881–90 |date=November 2007 | pmid = 17971784 | doi = 10.1038/nrd2445 | s2cid = 205476574 }}</ref>