Assessing the pharmacokinetic profile of the CamMedNP natural products database: an in silico approach

Ntie-Kang, Fidele; Mbah, James A; Lifongo, Lydia L; Owono Owono, Luc C; Megnassan, Eugene; Meva'a Mbaze, Luc; Judson, Philip N; Sippl, Wolfgang; Efange, Simon MN

doi:10.1186/2191-2858-3-10

Organic and Medicinal Chemistry Letters

Table 1 Average pharmacokinetic property distributions of total CamMedNP library in comparison with various subsets

From: Assessing the pharmacokinetic profile of the CamMedNP natural products database: an in silico approach

	Library name	Subset
	CamMedNP	Drug-like	Lead-like	Fragment-like
Lib. size^a	1,859	1,122	520	81
No. compl.^b	881	807	422	45
MW (Da)^c	426.70	330.33	276.46	195.75
Log P^d	4.18	2.82	2.24	1.42
HBA^e	5.85	5.18	4.39	3.53
HBD^f	2.39	1.40	1.29	0.81
NRB^g	5.31	4.51	3.39	2.06
Log B/B^h	−1.30	−0.77	−0.64	−0.36
BIP _Caco-2 (nm s⁻¹)ⁱ	1,199.37	1,216.27	1,207.91	1,577.16
S _mol (Å²)^j	696.28	569.69	501.44	393.20
S _mol,hfob (Å²)^k	409.24	280.66	200.91	131.61
V _mol (Å³)^l	1,304.41	1,024.64	870.65	645.16
LogS _wat (S in mol L⁻¹)^m	−5.11	−3.87	−3.13	−1.77
LogK _HSA ⁿ	0.46	0.15	−0.05	−0.44
MDCK^o	661.25	671.02	663.83	907.31
Ind_coh ^p	0.013	0.009	0.009	0.006
Glob^q	0.84	0.86	0.88	0.92
QP_polrz (Å³)^r	42.47	33.56	28.23	19.86
LogHERG^s	−4.64	−4.41	−4.22	−3.40
LogK _p ^t	−2.96	−2.86	−2.89	−2.63
#metab^u	5.56	4.62	3.57	2.07

^aSize or number of compounds in library; ^bnumber of compounds with #star = 0; ^cmolar weight (range for 95% of drugs is 130 to 725 Da); ^dlogarithm of partitioning coefficient between n-octanol and water phases (range for 95% of drugs is −2 to 6); ^enumber of hydrogen bonds accepted by the molecule (range for 95% of drugs is 2 to 20); ^fnumber of hydrogen bonds donated by the molecule (range for 95% of drugs is 0 to 6); ^gnumber of rotatable bonds (range for 95% of drugs is 0 to 15); ^hlogarithm of predicted blood/brain barrier partition coefficient (range for 95% of drugs is −3.0 to 1.0); ⁱpredicted apparent Caco-2 cell membrane permeability in Boehringer-Ingelheim scale, in nm/s (range for 95% of drugs is <5 low, >100 high); ^jtotal solvent-accessible molecular surface, in Å² (probe radius 1.4 Å; range for 95% of drugs is 300 to 1,000 Å²); ^khydrophobic portion of the solvent-accessible molecular surface, in Å² (probe radius 1.4 Å; range for 95% of drugs is 0 to 750 Å²); ^ltotal volume of molecule enclosed by solvent-accessible molecular surface, in Å³ (probe radius 1.4 Å; range for 95% of drugs is 500 to 2,000 Å³); ^mlogarithm of aqueous solubility in g/dm³ (range for 95% of drugs is −6.0 to 0.5); ⁿlogarithm of predicted binding constant to human serum albumin (range for 95% of drugs is −1.5 to 1.2); ^opredicted apparent MDCK cell permeability in nm/sec (<25 poor, >500 great); ^pindex of cohesion interaction in solids (0.0 to 0.05 for 95% of drugs); ^qglobularity descriptor (0.75 to 0.95 for 95% of drugs); ^rpredicted polarizability (13.0 to 70.0 for 95% of drugs); ^spredicted IC₅₀ value for blockage of HERG K⁺ channels (concern <−5); ^tpredicted skin permeability (−8.0 to −1.0 for 95% of drugs); ^unumber of likely metabolic reactions (range for 95% of drugs is 0 to 15).

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