Are there differences between launched drugs, clinical candidates, and commercially available compounds?
To clarify the differences between commercially available compounds, clinical candidates, and launched drugs with regard to distribution of physicochemical properties and to characterize the correlation between physicochemical properties, we conducted analyses on physicochemical descriptors of commercially available compounds, clinical candidates, and launched drugs. Initial analysis of the marginal distribution of each physicochemical property showed that the distribution of commercially available compounds obeys a more normal distribution than that of launched drugs and clinical candidates. In addition, we calculated correlation coefficient values between values of physicochemical properties and found little similarity between values of clinical candidates and those of commercially available compounds, while observing marked similarity between values of clinical candidates and those of launched drugs. We also analyzed joint distribution for two physicochemical properties, with results showing that, similar to marginal distribution, the joint distribution of commercially available compounds obeys a more normal distribution than that of launched drugs and clinical candidates. We then assessed items using the Nagahara method, originally developed by one of this study's authors. Results showed that the probability distribution of molecular weight and log P for commercially available compounds was much narrower than that of launched drugs and clinical candidates. In conclusion, clinical candidates are more similar to launched drugs than to commercially available compounds with regard to marginal distribution, joint distribution, and correlation coefficients. These findings provide deeper insight regarding the concept of "druglikeness".
Ohno
Kazuki
K
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Nagahara
Yuichi
Y
Tsunoyama
Kazuhisa
K
Orita
Masaya
M
D055598:Chemical Phenomena; D016208:Databases, Factual; D015195:Drug Design; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000737:chemistry*
D004364:Pharmaceutical Preparations