A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development.
This manuscript describes a comparison of the physicochemical properties of marketed oral drugs with those of 45 structurally confirmed orally bioavailable anti-cancer protein kinase inhibitors currently in different phases of clinical development. It is evident from the data presented that these kinase inhibitors are on average larger (over 110 Da), more lipophilic (over 1.5 log units) and more complex (approximately two more rotatable bonds) than those of marketed oral drugs. In contrast, hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) counts are not significantly different.
Gill
Adrian L
AL
Astex Therapeutics, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK. andrian.gill@astrazeneca.com
Verdonk
Marcel
M
Boyle
Robert G
RG
Taylor
Richard
R
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D004364:Pharmaceutical Preparations; D047428:Protein Kinase Inhibitors