Tariquidar

• CAT Number: I002592
• CAS Number: 206873-63-4
• Molecular Formula: C₃₈H₃₈N₄O₆
• Molecular Weight: 646.73
• Purity: ≥95%
• Synonyms: N-[2-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]-4,5-dimethoxyphenyl]quinoline-3-carboxamide
• Target: P-gp
• Solubility: in DMSO > 10 mM
• Storage: 2-8°C
• IC50: 5.1 nM (Kd)
• InChI: InChI=1S/C38H38N4O6/c1-45-33-18-25-14-16-42(23-28(25)19-34(33)46-2)15-13-24-9-11-29(12-10-24)40-38(44)30-20-35(47-3)36(48-4)21-32(30)41-37(43)27-17-26-7-5-6-8-31(26)39-22-27/h5-12,17-22H,13-16,23H2,1-4H3,(H,40,44)(H,41,43)
• InChIKey: LGGHDPFKSSRQNS-UHFFFAOYSA-N
• SMILES: COC1=C(C=C2CN(CCC2=C1)CCC3=CC=C(C=C3)NC(=O)C4=CC(=C(C=C4NC(=O)C5=CC6=CC=CC=C6N=C5)OC)OC)OC

Tariquidar（Cat No.:I002592）, also known as XR9576, is a potent and selective inhibitor of P-glycoprotein (P-gp), a drug efflux pump involved in multidrug resistance (MDR) in cancer cells. It exhibits a high affinity (Kd) of 5.1 nM for P-gp inhibition in the CHrB30 cell line. By blocking the activity of P-gp, Tariquidar effectively reverses drug resistance in MDR cell lines, enhancing the intracellular accumulation of chemotherapeutic drugs and increasing their efficacy.

Reference

1. Muz B, Kusdono HD, Azab F, de la Puente P, Federico C, Fiala M, Vij R, Salama NN, Azab AK. Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance. *Leuk Lymphoma*. 2017 May 16:1-10. doi: 10.1080/10428194.2017.1319052. [Epub ahead of print] PMID: 28509582.

2. Yi X, Zhao D, Zhang Q, Xu J, Yuan G, Zhuo R, Li F. Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance. *Nanotechnology*. 2017 Feb 24;28(8):085603. doi: 10.1088/1361-6528/aa5715. Epub 2017 Jan 5. PMID: 28055982.

3. Srinivas NR. Understanding the role of tariquidar, a potent Pgp inhibitor, in combination trials with cytotoxic drugs: What is missing? *Cancer Chemother Pharmacol*. 2016 Nov;78(5):1097-1098. Epub 2016 May 13. No abstract available. PMID: 27178178.

4. Zou W, Sarisozen C, Torchilin VP. The reversal of multidrug resistance in ovarian carcinoma cells by co-application of tariquidar and paclitaxel in transferrin-targeted polymeric micelles. *J Drug Target*. 2017 Mar;25(3):225-234. doi: 10.1080/1061186X.2016.1236113. Epub 2016 Oct 3. PMID: 27616277.

5. Bauer M, Blaickner M, Philippe C, Wadsak W, Hacker M, Zeitlinger M, Langer O. Whole-Body Distribution and Radiation Dosimetry of 11C-Elacridar and 11C-Tariquidar in Humans. *J Nucl Med*. 2016 Aug;57(8):1265-8. doi: 10.2967/jnumed.116.175182. Epub 2016 Apr 14. PMID: 27081167.

6. Kakarla P, Inupakutika M, Devireddy AR, Gunda SK, Willmon TM, Ranjana KC, Shrestha U, Ranaweera I, Hernandez AJ, Barr S, Varela MF. 3D-QSAR AND CONTOUR MAP ANALYSIS OF TARIQUIDAR ANALOGUES AS MULTIDRUG RESISTANCE PROTEIN-1 (MRP1) INHIBITORS. *Int J Pharm Sci Res*. 2016 Feb;7(2):554-572. Epub 2016 Feb 1. PMID: 26913287. Free PMC Article.

7. Shayanfar S, Shayanfar A, Ghandadi M. Image-Based Analysis to Predict the Activity of Tariquidar Analogs as P-Glycoprotein Inhibitors: The Importance of External Validation. *Arch Pharm (Weinheim)*. 2016 Feb;349(2):124-31. doi: 10.1002/ardp.201500333. Epub 2015 Dec 28. PMID: 26708190.

8. Weidner LD, Fung KL, Kannan P, Moen JK, Kumar JS, Mulder J, Innis RB, Gottesman MM, Hall MD. Tariquidar Is an Inhibitor and Not a Substrate of Human and Mouse P-glycoprotein. *Drug Metab Dispos*. 2016 Feb;44(2):275-82. doi: 10.1124/dmd.115.067785. Epub 2015 Dec 10. PMID: 26658428. Free PMC Article.

9. Loo TW, Clarke DM. Mapping the Binding Site of the Inhibitor Tariquidar That Stabilizes the First Transmembrane Domain of P-glycoprotein. *J Biol Chem*. 2015 Dec 4;290(49):29389-401. doi: 10.1074/jbc.M115.695171. Epub 2015 Oct 26. PMID: 26507655. Free PMC Article.

10. Fox E, Widemann BC, Pastakia D, Chen CC, Yang SX, Cole D, Balis FM. Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors. *Cancer Chemother Pharmacol*. 2015 Dec;76(6):1273-83. doi: 10.1007/s00280-015-2845-1. Epub 2015 Oct 20. PMID: 26486517.