Table 1. Percentage of drugs satisfying the different efficiency (LEI, LLE), dose and physicochemical parameter criteria recently recommended. Comparison of average DTI values against these widely used parameters for lead optimization suggests that a DTI criterion of <1 is better in many cases and equal in others (except for antineoplastic and antiviral drugs). For PD on target/off target, PK and physicochemical contributions to DTI, the respective average values have been used as cut-off criteria (see ESI).

WHO ATC drug category	LEI > 0.3	LLE > 5	PD on target	PK	Physicochemical Log D	PD off target			DTI < 1	Exposure based TI, % of IC50/Cmax values between 0.5–2	Dose < 100 mg	ACD log D < 3	log P < 3
						CYP450	hERG	BSEP
Musculoskeletal	58	24	71	89	84	84	95	89	84	13	34	97	55
Antiparasitic	45	18	73	82	91	100	91	82	a 55	0	27	82	73
Antibiotic	36	54	94	86	80	84	86	76	b 54	0	0	90	80
Metabolic and GIT	46	63	83	96	83	83	83	90	77	17	69	90	79
CNS	69	44	94	86	84	90	85	90	73	21	68	84	62
Systemic and hormonal	45	55	82	91	91	82	100	82	91	9	82	82	64
Withdrawn	53	67	18	14	01	11	18	9	c 50	0	43	24	43
Gentio-Urinary and Sex	40	38	98	98	90	90	88	90	85	20	80	48	38
Antiviral	24	61	80	73	93	76	85	76	d 51	7	17	56	39
Respiratory	61	31	89	78	83	89	83	92	83	17	75	75	47
Blood	33	27	93	87	87	87	80	87	73	13	53	73	40
Cardiovascular	37	31	86	98	89	86	89	88	74	11	63	70	48
Antineoplastic	35	56	82	85	90	85	81	87	43	10	35	62	50
Average across therapeutic area	45	44	80	82	80	81	82	80	69	11	50	72	55