Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM2KITF)

• Drug Name: LY335979 Drug Info
• Synonyms: Zosuquidar HCl; Zosuquidar Trihydrochloride; LY 335979; LY-335979; Zosuquidar (TN); Zosuquidar trihydrochloride (USAN); RS-33295-198; Zosuquidar trihydrochloride, RS-33295-198, LY335979; (R)-4-((1aR,6R,10bS)-1,2-Difluoro-1,1a,6,10b-tetrahydrodibenzo(a,e)cyclopropa(c)cycloheptan-6-yl)-alpha-((5-quinoloyloxy)methyl)-1-piperazineethanol, trihydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Discontinued in Phase 3	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 153997
  CAS Number: CAS 167465-36-3
  TTD Drug ID: DM2KITF

Molecule-Related Drug Atlas

Drug(s) Targeting Multidrug resistance protein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
EDP-322	DMWTVM1	Bacterial infection	1A00-1C4Z	Phase 1	[4]
W-198	DMJ2R69	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
CBT-1	DM097UP	Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[6]
Biricodar	DM65JCM	Ovarian cancer	2C73	Discontinued in Phase 2	[7]
Tariquidar	DMJG7VP	Adrenocortical carcinoma	2D11.Z	Discontinued in Phase 2	[8]
Elacridar	DMURVE8	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[9]
ONT-093	DMB8T5U	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[10]
TRISMETHOXYRESVERATROL	DM6USPC	Discovery agent	N.A.	Investigative	[11]
[1,1':2',1'']-terphenyl-4,3'',5''-triol	DMVOY4D	Discovery agent	N.A.	Investigative	[11]
XR-9456	DMTUFI1	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Multidrug resistance protein 3 (ABCB4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Encequidar	DMM8Z3Q	Metastatic breast cancer	2C6Y	Phase 2	[13]
Dofequidar fumarate	DMWMHU7	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 3	[14]
Dexniguldipine	DMLZIT2	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[15]
LANIQUIDAR	DM3YABD	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[16]

Drug(s) Affected By ATP-dependent translocase ABCB1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[17]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[18]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[19]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[20]
Cepharanthine	DM9Y5JB	N. A.	N. A.	Approved	[21]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[22]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[23]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[24]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[25]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Multidrug resistance protein 1 (ABCB1)	TT3OT40	MDR1_HUMAN	Modulator	[2]
Multidrug resistance protein 3 (ABCB4)	TTJUXV6	MDR3_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005159)
• [2] A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxoru... Clin Cancer Res. 2004 May 15;10(10):3265-72.
• [3] Clinical disposition, metabolism and in vitro drug-drug interaction properties of omadacycline. Xenobiotica. 2017 Aug;47(8):682-696. doi: 10.1080/00498254.2016.1213465. Epub 2016 Aug 8.
• [4] In vitro activities of the novel bicyclolides modithromycin (EDP-420, EP-013420, S-013420) and EDP-322 against MDR clinical Neisseria gonorrhoeae isolates and international reference strains. J Antimicrob Chemother. 2015 Jan;70(1):173-7.
• [5] Mechanisms of tetrandrine and 5-bromotetrandrine in reversing multidrug resistance may relate to down-regulation of multidrug resistance associated protein 7 expression. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012 Jun;20(3):558-63.
• [6] A pharmacodynamic study of the P-glycoprotein antagonist CBT-1 in combination with paclitaxel in solid tumors. Oncologist.2012;17(4):512.
• [7] ClinicalTrials.gov (NCT00003847) VX-710, Doxorubicin, and Vincristine for the Treatment of Patients With Recurrent Small Cell Lung Cancer. U.S. National Institutes of Health.
• [8] Inhibition of P-glycoprotein (ABCB1)- and multidrug resistance-associated protein 1 (ABCC1)-mediated transport by the orally administered inhibitor, CBT-1((R)).Biochem Pharmacol.2008 Mar 15;75(6):1302-12.
• [9] 2-[(3-Methoxyphenylethyl)phenoxy]-based ABCB1 inhibitors: effect of different basic side-chains on their biological properties. J Med Chem. 2008 Dec 11;51(23):7602-13.
• [10] A phase I pharmacokinetic study of the P-glycoprotein inhibitor, ONT-093, in combination with paclitaxel in patients with advanced cancer. Invest New Drugs. 2005 Aug;23(4):311-5.
• [11] Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells. J Med Chem. 2006 May 18;49(10):3012-8.
• [12] Functional assay and structure-activity relationships of new third-generation P-glycoprotein inhibitors. Bioorg Med Chem. 2008 Mar 1;16(5):2448-62.
• [13] Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem. 2021 Apr 8;64(7):3677-3693.
• [14] Reversal of multidrug resistance by a novel quinoline derivative, MS-209. Cancer Chemother Pharmacol. 1995;35(4):271-7.
• [15] Mechanism of action of dexniguldipine-HCl (B8509-035), a new potent modulator of multidrug resistance. Biochem Pharmacol. 1995 Mar 1;49(5):603-9.
• [16] Evaluation of [11C]laniquidar as a tracer of P-glycoprotein: radiosynthesis and biodistribution in rats. Nucl Med Biol. 2009 Aug;36(6):643-9.
• [17] Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists. Cancer Res. 1994 Feb 1;54(3):730-7.
• [18] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [19] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [20] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [21] Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci. 2005 Jun;96(6):372-6. doi: 10.1111/j.1349-7006.2005.00057.x.
• [22] Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
• [23] Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• [24] Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
• [25] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.