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

General Information of Drug (ID: DMJZ0AM)

• Drug Name: GERANYLGERANYL DIPHOSPHATE Drug Info
• Synonyms: Geranylgeranyl pyrophosphate; Geranylgeranyl diphosphate; GGDP; 6699-20-3; geranylgeranyl-PP; GGPP; UNII-N21T0D88LX; (2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl trihydrogen diphosphate; N21T0D88LX; Geranylgeraniol diphosphate; CHEBI:48861; all-trans-Geranylgeranyl pyrophosphate; all-trans-Geranylgeranyl diphosphate; Diphosphoric acid, mono(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl) ester, (E,E,E)-; Geranylgeranyl pyrophosphate ammonium salt; 2-trans,6-trans,10-trans-geranylgeranyl diphosphate

Indication

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

• Cross-matching ID:
  PubChem CID: 447277
  ChEBI ID: CHEMBL48861
  CAS Number: CAS 6699-20-3
  TTD Drug ID: DMJZ0AM

Molecule-Related Drug Atlas

Drug(s) Targeting Farnesyl protein transferase (Ftase)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lonafarnib	DMGM2Z6	Hutchinson-Gilford progeria syndrome	LD2B	Approved	[4]
Zarnestra	DMF30HL	Acute myeloid leukaemia	2A60	Phase 3	[5]
L-778123	DMWSC5L	Lymphoma	2A80-2A86	Phase 1	[6]
GGTI-2418	DM8U23L	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
BMS214662	DM5M48F	Non-small-cell lung cancer	2C25.Y	Phase 1	[8]
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[9]
ABT-839	DM4UN9A	Non-small-cell lung cancer	2C25.Y	Terminated	[10]
MANUMYCIN A	DM1SWOY	N. A.	N. A.	Terminated	[11]
SCH-44342	DMUL4VX	N. A.	N. A.	Terminated	[12]
RPR-113829	DMJ63GW	N. A.	N. A.	Terminated	[13]

Drug(s) Targeting CAAX farnesyltransferase beta (FNTB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[9]
ABT-839	DM4UN9A	Non-small-cell lung cancer	2C25.Y	Terminated	[14]
MANUMYCIN A	DM1SWOY	N. A.	N. A.	Terminated	[11]
SCH-44342	DMUL4VX	N. A.	N. A.	Terminated	[9]
RPR-113829	DMJ63GW	N. A.	N. A.	Terminated	[13]
RPR-114334	DMAIJT6	N. A.	N. A.	Terminated	[13]
L-731735	DM1XBKC	Solid tumour/cancer	2A00-2F9Z	Terminated	[9]
FUSIDIENOL	DMI1Y92	N. A.	N. A.	Terminated	[15]
ABT-100	DMPFLS5	Solid tumour/cancer	2A00-2F9Z	Terminated	[16]
B-956	DM1IO9X	Solid tumour/cancer	2A00-2F9Z	Terminated	[17]

Drug(s) Targeting Geranyltranstransferase (FDPS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[18]
Minodronate	DM50PMY	Osteoporosis	FB83.0	Approved	[19]
Ibandronate	DM0QZBN	Hypercalcaemia	5B91.0	Approved	[18]
Alendronate	DMY2KX9	Bone Paget disease		Approved	[18]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[20]
Incadronate	DM3DSVJ	Hypercalcaemia	5B91.0	Approved	[21]
Risedronate	DM5FLTY	Bone Paget disease		Approved	[22]
NERIDRONIC ACID	DMMPG5V	Bone disease	FC0Z	Approved	[23]
Zarnestra	DMF30HL	Acute myeloid leukaemia	2A60	Phase 3	[24]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Discovery agent	N.A.	Investigative	[2]

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	[25]
Selenium	DM25CGV	N. A.	N. A.	Approved	[26]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[30]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[31]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[32]
Tocopherol	DMBIJZ6	N. A.	N. A.	Phase 2	[26]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CAAX farnesyltransferase beta (FNTB)	TT7WZIJ	FNTB_HUMAN	Inhibitor	[2]
Farnesyl protein transferase (Ftase)	TTXQKM3	FNTA_HUMAN; FNTB_HUMAN	Inhibitor	[2]
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: 3052).
• [2] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [3] Variously substituted (phosphonoacetamido)oxy analogues of geranylgeranyl diphosphate (GGdP) as GGdP-transferase (GGTase) inhibitors and antiproliferative agents. Med Chem. 2005 May;1(3):239-44. doi: 10.2174/1573406053765512.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [5] Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
• [6] Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein trans... Mol Cancer Ther. 2002 Jul;1(9):747-58.
• [7] Company report (Prescient)
• [8] Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia. 2004 Oct;18(10):1599-604.
• [9] Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
• [10] Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.
• [11] A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
• [12] Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.
• [13] Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
• [14] Design and synthesis of o-trifluoromethylbiphenyl substituted 2-amino-nicotinonitriles as inhibitors of farnesyltransferase. Bioorg Med Chem Lett. 2005 Jan 3;15(1):153-8.
• [15] Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking. J Med Chem. 2002 Mar 28;45(7):1460-5.
• [16] Potent farnesyltransferase inhibitor ABT-100 abrogates acute allograft rejection. J Heart Lung Transplant. 2005 Sep;24(9):1403-9.
• [17] Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res. 1995 Nov 15;55(22):5310-4.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [19] 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.
• [20] Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
• [21] 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.
• [22] Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14.
• [23] 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.
• [24] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [25] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [26] 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.
• [27] 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.
• [28] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [29] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [30] 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.
• [31] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [32] 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.
• [33] 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.