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

General Information of Drug (ID: DMIXC7G)

• Drug Name: Zoledronate Drug Info
• Synonyms: Aclasta; Reclast; ZOL; Zometa; Novartis brand of zoledronic acid; Zoledronic acid; Zometa Concentrate; Bisphosphonate 3; CGP 42446; CGP 42446A; Aclasta (TN); CGP 42'446; CGP-42446; KS-1132; Reclast (TN); Zoledronic acid (INN); Zoledronic acid [USAN:INN]; Zomera (TN); Zometa (Novartis); Zometa (TN); CGP-42'446; Zometa, Zomera, Aclasta and Reclast, Zoledronic Acid; [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid); (1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid; (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid; (1-hydroxy-2-imidazol-1-yl-phosphonoethyl)phosphonic acid monohydrate; 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid; 2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid

Indication

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[1]

• Therapeutic Class: Bone Density Conservation Agents
• Cross-matching ID:
  PubChem CID: 68740
  ChEBI ID: CHEBI:46557
  CAS Number: CAS 118072-93-8
  TTD Drug ID: DMIXC7G
  VARIDT Drug ID: DR01473

Molecule-Related Drug Atlas

Drug(s) Transported By Multidrug resistance-associated protein 1 (ABCC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[5]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[6]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[9]
Irinotecan	DMP6SC2	Colorectal cancer	2B91.Z	Approved	[10]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[11]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[12]
Daunorubicin	DMQUSBT	Acute myeloid leukaemia	2A60	Approved	[13]

Drug(s) Targeting Geranyltranstransferase (FDPS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Minodronate	DM50PMY	Osteoporosis	FB83.0	Approved	[14]
Ibandronate	DM0QZBN	Osteoporosis	FB83.0	Approved	[2]
Alendronate	DMY2KX9	Osteoporosis	FB83.0	Approved	[2]
Pamidronate	DMB4AVP	Hypercalcaemia	5B91.0	Approved	[15]
Incadronate	DM3DSVJ	Hypercalcaemia	5B91.0	Approved	[16]
Risedronate	DM5FLTY	Paget's disease	FB85	Approved	[17]
NERIDRONIC ACID	DMMPG5V	Bone disease	FC0Z	Approved	[18]
Zarnestra	DMF30HL	Acute myeloid leukaemia	2A60	Phase 3	[19]
GERANYLGERANYL DIPHOSPHATE	DMJZ0AM	Discovery agent	N.A.	Investigative	[20]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Discovery agent	N.A.	Investigative	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Geranyltranstransferase (FDPS)	TTIKWV4	FPPS_HUMAN	Modulator	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[3]

References

• [1] Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study. Cell Biol Int. 2006 Mar;30(3):278-82.
• [4] The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer. 2005 Jul 11;93(1):89-97.
• [5] Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
• [6] Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
• [7] Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins. Cancer Gene Ther. 2001 Oct;8(10):803-14.
• [8] Multidrug resistance-associated protein-1 functional activity in Calu-3 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205.
• [9] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [10] ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8.
• [11] Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3). Drug Metab Dispos. 2008 Dec;36(12):2571-81.
• [12] Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010 Jun;58(7):1019-32.
• [13] Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
• [14] Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid. J Med Chem. 2010 May 13;53(9):3454-64.
• [15] Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
• [16] Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42.
• [17] Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14.
• [18] Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of hu... J Med Chem. 2008 Apr 10;51(7):2187-95.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.