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. Author manuscript; available in PMC: 2023 Jun 24.
Published in final edited form as: Pharmacol Ther. 2022 Oct 22;240:108300. doi: 10.1016/j.pharmthera.2022.108300

Table 5:

Clinical Drugs/Inhibitors Inhibiting ENT And CNT-mediated Nucleoside Transport

Drug Type Name Cell lines/animals Dose Transporter [3H]nucleosidee uptake (%Inhibition/IC50) Reference
Nucleoside Reverse Transcriptase inhibitor (NRTIs) Entecavir (ETV) HeLa 1mM ENT1
ENT2		 3.05±1.56mM ([3H] uridine)
2.07±0.29mM ([3H] uridine)		 (Miller, et al., 2020)
Abacavir (ABC) 1mM ENT1
ENT2		 0.11±0.02mM ([3H] uridine)
0.22±0.01mM ([3H] uridine)
Zidovudine (AZT) 1mM ENT1
ENT2		 2.54±0.26mM ([3H] uridine)
1.64±0.36mM ([3H] uridine)
Pyrimidopyrimidines and Pteridines Dipyridamole PK15NTD 10μM ENT1
ENT2		 5.0±0.9nM ([3H]NBMPR)
356±13nM ([3H]NBMPR)		 (Boswell-Casteel & Hays, 2017; Boyer, Karjian, Wahl, Pegram, & Neuteboom, 2002; Ward, et al., 2000; J. D. Young Yao, Sun, Cass, & Baldwin, 2008);
Alkyl, Cycloalkyldiamine and Piperazine compounds Dilazep PK15NTD (hENT1 and hENT2)
H9c2 (rENT2)		 10μM ENT1
ENT2		 17.5nM ([3H]-5-uridine)
8800nM ([3H]-5-uridine)		 (Playa, et al., 2014)
Draflazine U-2 OS 10-11 to 10-6 ENT1



ENT2		 5.3nM ([3H]adenosine) 15.85nM ([3H]adenosine)
16.0± 5.9nM ([3H] uridine)
2400± 400nM ([3H] uridine)		 (Bohm, et al., 1994; Hammond, 2000; Noji, Karasawa, & Kusaka, 2004; Vlachodimou, Konstantinopoulou, AP, & Heitman, 2020)
Cannabinoids Tetrahydrocannabinol (THC) EOC-20 RAW264.7 100–1000nM ENT1 0.17μM ([3H]thymidine)
0.27μM ([3H]adenosine)		 (Carrier, et al., 2006; Stollenwerk, Pollock, & Hillard, 2021)
Cannabidiol (CBD) 100–1000nM ENT1 0.19μM ([3H]thymidine)
0.12μM ([3H]adenosine)
Quinolinone derivative Cilostazol (Pletal) Cardiac ventricular myocytes, Coronary artery smooth muscle, Endothelial cells 5–10μM ENT1 ~10μM (EC50 ([3H]adenosine) (Y. Liu, et al., 2000)
Receptor inhibitors Propentofylline L1210/B23.1 cells; L1210/C2; Walker 256; L1210/MA27.1 es


ei


cif 		9μM ([3H]adenosine)


170μM ([3H]adenosine)

6mM ([3H]adenosine)		 (Parkinson, Paterson, Young, & Cass, 1993; Parkinson, Rudolphi, & Fredholm, 1994)
Ticagrelor MDCK 0.1–100 nM/L; 1–100 μM/L ENT1

ENT2		 6.59+0.09μM ([3H]adenosine)
4.76+0.03μM ([3H]adenosine)		 (Armstrong, et al., 2014)
Thiazolidinediones Troglitazone HASMC 30μM ENT1 2.35±0.35μM ([3H]adenosine)
4.38±0.34μM ([3H]uridine) 3.99±0.57μM ([3H]NBMPR)		 (Leung, Man, & Tse, 2005)
Pioglitazone 30μM ENT1 13% ([3H]adenosine)
Ciglitazone 30μM ENT1 8% ([3H]adenosine)
Antiviral drugs Remdesivir HeLa - ENT1
ENT2		 38±2μM ([3H]uridine)
73±14μM ([3H]uridine)		 (Miller, et al., 2021)
EIDD-1931 - ENT1
ENT2		 259±118μM ([3H]uridine)
467±101μM ([3H]uridine)
Molnupiravir - ENT1
ENT2		 701±294μM ([3H]uridine)
851±152μM ([3H]uridine)
Dihydrochalcones Phloridzin - - CNT3 16±0.01μM (Ki) (Gupte & Buolamwini, 2009)
Tyrosine kinase inhibitors (TKIs) Erlotinib AsPc-1 A549, H292, H1975 cells, Yeast 0–100μM CNT1
CNT3
ENT1		 160±20μM ([3H]-uridine)
11±1μM ([3H]-uridine)
1.6±0.4 to 34±6μM ([3H]-uridine)		 (Damaraju, et al., 2014)
Gefitinib CNT1
ENT1		 37±11μM ([3H]-uridine)
2.0±0.6 to 14±6μM ([3H]-uridine)
Vandetanib CNT1
CNT2
CNT3
ENT1
ENT2		 64±17μM ([3H]-uridine)
82±4μM ([3H]-uridine)
28±9μM ([3H]-uridine)
11±1 to 33±8μM ([3H]-uridine)
89±17μM ([3H]-uridine)
Imatinib Saccharomyces cerevisiae 0–300μM CNT2

ENT1		 2.3μM ([3H]uridine)

110μM ([3H]uridine)		 (Damaraju, Weber, Kuzma, Cass, & Sawyer, 2016)
Dasatinib ENT1 60μM ([3H]uridine)
Bosutinib ENT1 13μM ([3H]uridine)
Nilotinib ENT1 0.7μM ([3H]uridine)
Ponatinib ENT1 9μM ([3H]uridine)
Abemaciclib HAP1-ENT2 KO 10μM ENT1 25.0±7.9% ([3H]-uridine) (Jouan, et al., 2021)
Acalabrutinib 10μM ENT1 42.6±10.4% ([3H]-uridine)
Afatinib 10μM ENT1 54.5±2.4% ([3H]-uridine)
Alectinib 10μM ENT1 54.0±4.9% ([3H]-uridine)
Brigatinib 10μM ENT1 52.5±11.1% ([3H]-uridine)
Cabozantinib 10μM ENT1 48.8±2.5% ([3H]-uridine)
Ceritinib 10μM ENT1 26.3±1.7% ([3H]-uridine)
Crizotinib 10μM ENT1 34.7±2.7% ([3H]-uridine)
Dacomitinib 10μM ENT1 43.9±2.3% ([3H]-uridine)
Entrectinib 10μM ENT1 22.9±5.2% ([3H]-uridine)
Ibrutinib 10μM ENT1 72.7±1.1% ([3H]-uridine)
Itacitinib 10μM ENT1 21.9±13.3% ([3H]-uridine)
Lapatinib 10μM ENT1 25.7±15.2% ([3H]-uridine)
Lenvatinib 10μM ENT1 63.1±5.9% ([3H]-uridine)
Lorlatinib 10μM ENT1 86.6±6.4% ([3H]-uridine)
Neratinib 10μM ENT1 61.0±8.5% ([3H]-uridine)
Nintedanib 10μM ENT1 46.9±9.6% ([3H]-uridine)
Osimertinib 10μM ENT1 32.3±11.3% ([3H]-uridine)
Pacritinib 10μM ENT1 61.6±8.1% ([3H]-uridine)
Regorafenib 10μM ENT1 21.4±2.7% ([3H]-uridine)
Ribociclib 10μM ENT1 17.8±10.2% ([3H]-uridine)
Ruxolitinib 10μM ENT1 34.1±13.2% ([3H]-uridine)
Tofacitinib 10μM ENT1 4.8±8.3% ([3H]-uridine)
Vemurafenib 10μM ENT1 27.3±10.9% ([3H]-uridine)
Inhibitors not approved for drug use S-(4-nitrobenzyl)-6-thioinosine (NBMPR) PK15NTD 1μM ENT1, 2 0.4± 0.1nM ([3H]NBMPR)
2.8±0.3mM ([3H]NBMPR)		 (Ward, et al., 2000)
FPMINT 10nM-100μM ENT1
ENT2		 8.04±1.04μM ([3H]-uridine)
1.34±0.154μM ([3H]-uridine)		 (R. Li, et al., 2022)
Rapadocin 10μM ENT1 3.3nM ([3H]-thymidine) (Y. Wang, et al., 2021)