. Author manuscript; available in PMC: 2020 Dec 12.

Published in final edited form as: J Med Chem. 2019 Nov 26;62(23):10645–10663. doi: 10.1021/acs.jmedchem.9b00966

Table 2.

Increased Toxicity of Paclitaxel to DU145TXR in the Presence of P-gp Inhibitors Identified by ChemGen/Docking Routine^a

inhibitor concentration	resensitization to paclitaxel with the indicated treatment and fold-increased sensitivity in the presence of inhibitors
	PTX alone	PTX + 29			PTX + 216			PTX + 227			PTX + 231			PTX + 541			PTX + 551
	IC₅₀ PTX (nM)	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29	IC₅₀ PTX (nM)	fold vs PTX	fold vs PTX + 29
3 μM	2120	629	3	1	266	8	2.4	164	13	3.8	153	14	4.1	426	5	1.5	56	38	11
5 μM	2120	194	11	1	154	14	1.3	52	41	3.7	46	46	4.2	21	101	9.2	20	106	9.7
7 μM	2120	59	36	1	62	34	1	6	353	10	7	303	8.4	17	125	3.4	9	236	6.6
10 μM	2120	21	101	1	57	37	0.4	4	530	5	2	1060	11	17	125	3.4	6	353	3.5

Cytotoxicity of the chemotherapeutic paclitaxel (PTX) to P-gp-overexpressing prostate cancer cells, DU145TXR, was determined in the absence and presence of the ChemGen-designed 29-variants, 216, 227, 231, 541, and 551. For each experimental compound IC50 values of PTX alone or in the presence of inhibitors, fold improvement of PTX sensitivity in the presence of the inhibitor and fold improvement of PTX sensitivity by variants compared to parental compound 29 are given.