Structural Dynamics of P-Rex1 Complexed with Natural Leads Establishes the Protein as an Attractive Target for Therapeutics to Suppress Cancer Metastasis

Table 4

Computational druglikeness and pharmacokinetics of compounds.

	Property	Compound
		Top-1	Top-2
Physicochemical properties	Formula	C23H25ClN4O2S	C25H15ClF2N4O2
	Molecular weight	456.99 g/mol	476.86 g/mol
	Num. heavy atoms	31	34
	Num. arom. heavy atoms	16	24
	Fraction Csp3	0.39	0.04
	Num. rotatable bonds	5	4
	Num. H-bond acceptors	5	7
	Num. H-bond donors	0	2
	Molar refractivity	128.62	128.21
	TPSA	97.61 Å^2	87.47 Å^2
Lipophilicity	Consensus Log Po/w	4.72	4.78
Water solubility	Water solubility	Moderately soluble	Poorly soluble
Pharmacokinetics	GI absorption	High	High
	BBB permeant	No	No
	P-gp substrate	No	No
	CYP1A2 inhibitor	No	No
	CYP2C19 inhibitor	Yes	No
	CYP2C9 inhibitor	Yes	Yes
	CYP2D6 inhibitor	No	No
	CYP3A4 inhibitor	Yes	No
	Log Kp (skin permeation)	-5.64 cm/s	-5.53 cm/s
Druglikeness	Lipinski	Yes	Yes; 0 violation
	Ghose	Yes	No
	Veber	Yes	Yes
	Egan	Yes	No
	Muegge	Yes	No
	Bioavailability score	0.55	0.56
Medicinal chemistry	PAINS	0 alert	0 alert
	Brenk	0 alert	0 alert
	Synthetic accessibility	4.64	3.80
Toxicity	Hepatotoxicity	N0	Yes
	Skin sensitisation	No	No
	T. pyriformis toxicity	No	No
	AMES toxicity	No	No
	Minnow toxicity	No	No
	Carcino mouse	Negative	Negative
Excretion	Total clearance	-0.082	0.075
	Renal OCT2 substrate	No	No