Table 3.

Results of the ChEMBL-based ligand analysis

Target name	Hot Spot Structure	Total No. of ChEMBL ligands	Liganablea		Tractableb		Ro5 compliance
			LIGexp		LE/LLE		Ro5_3c		Ro5_4d		MW>500
			No.	%	No.	%	No.	%	No.	%	No.	%
HIV-1 Protease	Complex I	5638	3561	63.16	75	2.11	1922	53.97	183	5.14	3166	88.91
Heat Shock Protein 90	Complex I	841	335	39.83	92	27.46	326	97.31	247	73.73	69	20.6
Thrombin	Complex I	5921	2297	38.79	1230	53.55	2051	89.29	1057	46.02	1012	44.06
MAP Kinase P38	Complex I	4772	2548	53.39	408	16.01	2186	85.79	1509	59.22	506	19.86
Bromodomain BRD4	Complex I	1088	222	20.40	17	7.66	220	99.1	149	67.12	29	13.06
Renin	Complex I	4038	2813	69.66	392	13.94	1665	59.19	276	9.81	2413	85.78
PPAR-γ	Complex I	2134	917	42.97	1	0.11	405	44.17	108	11.78	531	57.91
MAP Kinase Kinase	Complex I	867	461	53.17	150	32.54	416	90.24	263	57.05	176	38.18
E3 ubiquitin-protein ligase XIAP	Complex I	1168	308	26.37	14	4.55	174	56.49	63	20.45	242	78.57
Epidermal Growth Factor Receptor	Complex II	7047	2959	41.99	504	17.03	2673	90.33	1963	66.34	801	27.07
Hepatocyte Growth Factor Receptor	Complex II	3864	2382	61.65	755	31.7	2042	85.73	1316	55.25	967	40.6
Anaplastic Lymphoma Kinase	Complex II	1688	1020	60.43	151	14.8	835	81.86	392	38.43	584	57.25
Tyrosine Protein Kinase ABL1	Complex II	2032	1084	53.35	401	36.99	963	88.84	678	62.55	296	27.31
VEGFR- 2	Complex II	8031	3894	48.49	688	17.67	3585	92.06	2597	66.69	839	21.55
Polo-like Kinase 1	Complex II	737	281	38.13	34	12.1	254	90.39	161	57.3	105	37.37
Glucocorticoid Receptor	Complex II	3510	2584	73.62	221	8.55	2146	83.05	930	35.99	752	29.1
Cyclophilin A	Complex III	231	74	32.03	1	1.35	12	16.22	10	13.51	59	79.73
Bcl-2	Complex III	865	427	49.36	3	0.7	109	25.53	41	9.6	361	84.54
DOT1-like Histone H3 Me-transferase	Complex III	100	42	42.00	28	66.67	40	95.24	5	11.9	34	80.95
FK506 Binding Protein	Complex III	491	156	31.77	4	2.56	62	39.74	32	20.51	110	70.51
FGFR1	Complex III	1605	661	41.18	87	13.16	624	94.4	369	55.82	270	40.85
Phosphoinositide-3 Kinase	Simple	1912	704	36.82	315	44.74	686	97.44	515	73.15	161	22.87
Protein Farnesyltransferase	Simple	2411	1204	49.94	373	30.98	1070	88.87	570	47.34	543	45.1
Kinesin Eg5	Simple	1060	396	37.36	105	26.52	362	91.41	287	72.47	55	13.89
HMG-CoA Reductase	Simple	287	199	69.34	26	13.07	154	77.39	91	45.73	64	32.16
Hepatitis C Virus NS5b Subunit	Simple	1267	302	23.84	57	18.87	227	75.17	128	42.38	128	42.38
Hepatitis C Virus NS34A Protease	Simple	498	254	51.00	1	0.39	212	83.46	1	0.39	249	98.03
Integrin Alpha-IIB	Simple	2436	1027	42.16	613	59.69	779	75.85	545	53.07	415	40.41
Smoothened Homolog	Simple	710	340	47.89	59	17.35	316	92.94	261	76.76	39	11.47
Na-K ATPase	Simple	223	55	24.66	11	20	47	85.45	22	40	24	43.64

^aLiganable - number, percent of compounds with pK_I > 7

^bTractable - number, percent of compounds with LE > 0.3 and LLE > 5, percent based on total ligandable

^aRo5_3 - number of ligands meeting 3 of the 4 Ro5 criteria;

^bRo5_4 - number of ligands meeting 4 of the 4 Ro5 criteria, percents based on total ligandable