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

General Information of Drug (ID: DM0QZBN)

• Drug Name: Ibandronate Drug Info
• Synonyms: BFQ; Acid ibandronico; Ibandronic Acid; Bisphosphonate 2; R484; RPR 102289A; Bondronat (TN); Boniva (TN); Bonviva (TN); Ibandronic acid (INN); Ibandronic acid [INN:BAN]; RPR-102289A; Ibandronic acid, sodium salt, monohydrate; Roche brand of ibandronic acid, sodium salt, monohydrate; [1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphonic acid; [1-HYDROXY-3-(METHYL-PENTYL-AMINO)-1-PHOSPHONO-PROPYL]-PHOSPHONIC ACID; (1-Hydroxy-3-(methylpentylamino)propylidene)diphosphonic acid; (1-hydroxy-3-(methylpentylamino)propylidene)bisphosphonate; 1-hydroxy-3-(methylpentylamino)propylidenebisphosphonate

Indication

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[1]
Osteoporosis	FB83.0	Approved	[2]

• Therapeutic Class: Bone Density Conservation Agents
• Cross-matching ID:
  PubChem CID: 60852
  ChEBI ID: CHEMBL997
  CAS Number: CAS 114084-78-5
  TTD Drug ID: DM0QZBN
  ACDINA Drug ID: D00319

Molecule-Related Drug Atlas

Drug(s) Targeting Geranyltranstransferase (FDPS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[3]
Minodronate	DM50PMY	Osteoporosis	FB83.0	Approved	[5]
Alendronate	DMY2KX9	Bone Paget disease		Approved	[3]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[6]
Incadronate	DM3DSVJ	Hypercalcaemia	5B91.0	Approved	[7]
Risedronate	DM5FLTY	Bone Paget disease		Approved	[8]
NERIDRONIC ACID	DMMPG5V	Bone disease	FC0Z	Approved	[9]
Zarnestra	DMF30HL	Acute myeloid leukaemia	2A60	Phase 3	[10]
GERANYLGERANYL DIPHOSPHATE	DMJZ0AM	Discovery agent	N.A.	Investigative	[11]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Discovery agent	N.A.	Investigative	[11]

Drug(s) Affected By Ras-related protein Rap-1A (RAP1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[12]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[15]
Minodronate	DM50PMY	Osteoporosis	FB83.0	Approved	[16]
Risedronate	DM5FLTY	Bone Paget disease		Approved	[17]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[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	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Ras-related protein Rap-1A (RAP1A)	OT5RH6TI	RAP1A_HUMAN	Post-Translational Modifications	[4]

References

• [1] Ibandronate FDA Label
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3059).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Extracellular calcium increases bisphosphonate-induced growth inhibition of breast cancer cells. Breast Cancer Res. 2008;10(1):R4. doi: 10.1186/bcr1845. Epub 2008 Jan 11.
• [5] 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.
• [6] Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
• [7] 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.
• [8] Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14.
• [9] 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.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [13] Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors. Cancer Res Commun. 2023 Dec 8;3(12):2497-2509. doi: 10.1158/2767-9764.CRC-23-0350.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [16] Efficacy of a nitrogen-containing bisphosphonate, minodronate, in conjunction with a p38 mitogen activated protein kinase inhibitor or doxorubicin against malignant bone tumor cells. Cancer Chemother Pharmacol. 2008 Jun;62(1):111-6. doi: 10.1007/s00280-007-0580-y. Epub 2007 Sep 15.
• [17] Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity. Bone. 2001 Oct;29(4):336-43. doi: 10.1016/s8756-3282(01)00589-0.
• [18] Synergistic interaction of lovastatin and paclitaxel in human cancer cells. Mol Cancer Ther. 2001 Dec;1(2):141-9.
• [19] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [20] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.