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 110Da), 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.