TABLE 1

Predicted physicochemical properties and experimentally determined LysoTracker Red IC₅₀ values for 27 compounds

All physicochemical properties were calculated with MarvinSketch 5.9.0 as described in the Materials and Methods; compounds that showed >25% LysoTracker Red inhibition at the highest tested concentration but did not yield an IC₅₀ value or exhibited concentration-dependent cytotoxicity were classified as possible for undergoing lysosomal sequestration.

Molecular Species	Drug	Drug Class	logP	logD_{pH 7.4}	PSA	Acidic or anionic	Basic or cationic	LysoTracker Red IC₅₀	Cytotoxicity (LDH release)	Evidence for lysosomal trapping
Molecular Species	Drug	Drug Class	logP	logD_{pH 7.4}	Å²	pK_a	pK_a	µM	Cytotoxicity (LDH release)	Evidence for lysosomal trapping
Acid	Diclofenac	NSAID	4.26	1.10	49.33	4.00	—	>500	Little or none	None
	Ibuprofen	NSAID	3.84	1.34	37.30	4.85	—	>500	Little or none	None
	Ketoprofen	NSAID	3.61	0.39	54.37	3.88	—	>500	Little or none	None
	Ketorolac	NSAID	2.28	−0.96	59.30	3.84	—	>500	Little or none	None
	Tenoxicam	NSAID	0.34	−0.71	99.60	3.63, 7.21	4.78	>500	Little or none	None
	Atorvastatin	Statin	5.39	2.44	111.79	4.33, 11.82	—	>500	Little or none	None
	Fluvastatin	Statin	3.83	1.06	82.69	4.56	—	>500	Little or none	None
	Pravastatin	Statin	1.65	−1.38	124.29	4.21	—	>500	Little or none	None
	Rosuvastatin	Statin	1.92	−1.24	140.92	4.00	—	>500	Little or none	None
Base	Fluoxetine	Antidepressant (SSRI)	4.17	1.83	21.26	—	9.80	150	Little or none	Yes
	Paroxetine	Antidepressant (SSRI)	3.15	0.83	39.72	—	9.77	130	Little or none	Yes
	Desipramine	Antidepressant (Tricyclic)	3.90	1.37	15.27	—	10.02	220	Little or none	Yes
	Imipramine	Antidepressant (Tricyclic)	4.28	2.48	6.48	—	9.20	260	Little or none	Yes
	Astemizole	Antihistamine	5.39	3.97	42.32	—	6.54, 8.75	110	Yes	Possible
	Amodiaquine	Antimalarial	4.53	2.24	48.39	9.12	6.46, 10.23	>500	Little or none	Possible
	Chloroquine	Antimalarial	3.93	0.88	28.16	—	7.29, 10.32	220	Little or none	Yes
	Dextromethorphan	Antitussive	3.49	1.08	12.47	—	9.85	>500	Little or none	Possible
	Labetalol	Beta blocker	2.97	1.26	95.58	8.05	9.80	>500	Little or none	Possible
	Propranolol	Beta blocker	2.58	0.36	41.49	—	9.67	92	Little or none	Yes
Neutral	Acetaminophen	Analgesic	0.91	0.90	49.33	9.46	—	>500	Little or none	None
	Erlotinib	Anticancer	3.20	3.20	74.73	—	4.59	>500	Little or none	None
	Gefitinib	Anticancer	3.75	3.64	68.74	—	4.51, 6.85	77	Little or none	Yes
	Lapatinib	Anticancer	4.64	4.43	106.35	—	3.80, 7.20	380	Yes	Possible
	Fluconazole	Antifungal antibiotic	0.56	0.56	81.65	12.71	1.96, 2.56	>500	Little or none	None
	Nifedipine	Calcium channel blocker	1.82	1.81	110.45	—	3.89	>500	Little or none	None
Zwitterion	Cetirizine	Antihistamine	3.58	0.74	53.01	3.60	2.12, 7.79	>500	Little or none	None
Zwitterion	Raclopride	Antipsychotic	3.29	2.03	61.80	6.26	8.47	>500	Little or none	None

LDH, lactate dehydrogenase; NSAID, nonsteroidal anti-inflammatory drug; PSA, polar surface area; SSRI, selective serotonin reuptake inhibitor.