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

General Information of Drug (ID: DMXK8BH)

• Drug Name: digeranyl bisphosphonate Drug Info
• Synonyms: digeranyl bisphosphonate; [(6E,11E)-2,6,12,16-tetramethyl-9-phosphonoheptadeca-2,6,11,15-tetraen-9-yl]phosphonic acid; bisphosphonate, 5; CHEMBL258994; GTPL3187; SCHEMBL14408741

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 11606263
  TTD Drug ID: DMXK8BH

Molecule-Related Drug Atlas

Drug(s) Targeting Geranyltranstransferase (FDPS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[4]
Minodronate	DM50PMY	Osteoporosis	FB83.0	Approved	[5]
Ibandronate	DM0QZBN	Hypercalcaemia	5B91.0	Approved	[4]
Alendronate	DMY2KX9	Bone Paget disease		Approved	[4]
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]

Drug(s) Affected By Geranylgeranyl pyrophosphate synthase (GGPS1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Selenium	DM25CGV	N. A.	N. A.	Approved	[13]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[14]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[3]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[18]
Tocopherol	DMBIJZ6	N. A.	N. A.	Phase 2	[13]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

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

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Geranylgeranyl pyrophosphate synthase (GGPS1)	OTVEHG28	GGPPS_HUMAN	Gene/Protein Processing	[3]

References

• [1] 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: 3187).
• [2] Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem. 2008 Sep 25;51(18):5594-607.
• [3] Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. Biochem Biophys Res Commun. 2007 Feb 23;353(4):921-5. doi: 10.1016/j.bbrc.2006.12.094. Epub 2006 Dec 21.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [19] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.