Lipinski rule-of-five

TABLE 1 Lipinski Rule of Five for Orally Active Compounds... 

There are, in addition to these simple functional group filters, a number of property-based filters that may be applied. These fdters take the form of calculated metrics, such as the Lipinski Rule of Five (LRoF Hydrogen-bond donors. Hydrogen-bond acceptors, Lipophilicity, Molecular weight). Solubility, total Polar Surface Area (tPS A), Blood-brain-barrier (BBB) Permeability, calculated metabolic filters (cADMET Absorption-Distribution-Metabolism-Excretion-Toxicity) and Bioavailability. 

The Lipinski Rule-of-Five almost certainly represents the first real attempt to identify a drug-like filter for molecular databases. Lipinski analysed the compounds within the World Drag Index that had progressed to Phase II clinical trials or better and discovered a simple set of rales that have been used extensively since their publication in 1997. The LRoF states that a compound may have lower membrane permeability or poorer absorption if two or more of the rules are violated. These rules are a compound should have no more than 5 hydrogen-bond donors, no more than... 

Lipinski rule of five A set of criteria for predicting the oral bioavailability of a compound on the basis of simple molecular properties (molecular weight. <500 log P. <5 number of hydrogen-bond donors. <5 and number of hydrogen-bond acceptors. < 10). Typically, the criteria are applied to a library to niter structures from the library before any synthesis takes place. Any structure exceeding two or more criteria Is rejected. 

Lipinski Rule of Five. 40. 55. 62 Lipitor. See Atorvastatin Lipophilicity.. 31. 65 Lipoprotcias clas.ses of. 657-658 metabolism of. 657-658 structure of. 657. 6S7f Lipotropins. 84.3-844 LiqucHed phenol. 221 Lisinopril. 645-646 Li.sier. Joseph. 217. 221 Lithane. See Lithium carbonate Lithium carbonate. 503 Lithium citrate. 503 Liver, drug metabolism in. 7—8. 66-68 LKTs. 820. 822 Local anesthetics. 676-694 alkaloids. 690... 

TABLE 25.2 Human Proteins with Identified Chemical Tools, by Gene Family, Lipinski rule-of-five... 

It is called Lipinski Rule of Five since the cutoffs values for each four parameters are all close to five or are a multiple of five. 

Table P6 Lipinski rule-of-five (R05) and related drug-like filters.

Fig. 4.1 The distribution of human drug targets by protein family from (A) the 277 unique proteins enumerated as drug targets against the 1995 marketed human pharmacopoeia (adapted from [Drews and Ryser pullout]) and (B) the 374 unique proteins determined by the 2002 revised census to be the targets of all Lipinski rule-of-five compliant small molecule compounds in all stages of drug development from preclinical phases through the post-market (adapted from online Table 1 in...

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