Details of the Drug

General Information of Drug (ID: DMSQRXW)

• Drug Name: SQ-32709
• Synonyms: farnesyl diphosphate; farnesyl pyrophosphate; (2E,6E)-Farnesyl diphosphate; trans,trans-Farnesyl diphosphate; all-trans-Farnesyl pyrophosphate; (all-E)-Farnesyl diphosphate; (E,E)-Farnesyl pyrophosphate; (2E,6E)-Farnesyl pyrophosphate; trans-Farnesyl pyrophosphate; 2-trans,6-trans-Farnesyl pyrophosphate; farnesyl-PP; (E,E)-Farnesyl diphosphate; 2-trans,6-trans-farnesyl diphosphate; trans-trans-farnesyl diphosphate; UNII-79W6B01D07; CHEBI:17407; trans,trans-Farnesyl pyrophosphate; Sq 32709; 13058-04-3; CHEMBL69330

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Discontinued in Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 382.33
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C15H28O7P2
  IUPAC Name: phosphono [(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl] hydrogen phosphate
  Canonical SMILES: CC(=CCC/C(=C/CC/C(=C/COP(=O)(O)OP(=O)(O)O)/C)/C)C
  InChI: InChI=1S/C15H28O7P2/c1-13(2)7-5-8-14(3)9-6-10-15(4)11-12-21-24(19,20)22-23(16,17)18/h7,9,11H,5-6,8,10,12H2,1-4H3,(H,19,20)(H2,16,17,18)/b14-9+,15-11+
  InChIKey: VWFJDQUYCIWHTN-YFVJMOTDSA-N
• Cross-matching ID:
  PubChem CID: 445713
  ChEBI ID: CHEBI:17407
  CAS Number: 372-97-4
  DrugBank ID: DB07780
  TTD ID: D0N5HO
  INTEDE ID: DR1927

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Squalene synthetase (FDFT1)	TTFQEO5	FDFT_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Ras proteins prenyltransferase alpha (FNTA)	DEFNVD7	FNTA_HUMAN	Substrate	[3]
Squalene synthase (FDFT1)	DEIDTHQ	FDFT_HUMAN	Substrate	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Arteriosclerosis
• ICD Disease Classification: BD40

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Squalene synthetase (FDFT1)	DTT	FDFT1	7.85E-01	-0.09	-0.38
Squalene synthase (FDFT1)	DME	FDFT1	7.85E-01	-9.18E-02	-3.76E-01
Ras proteins prenyltransferase alpha (FNTA)	DME	FNTA	6.96E-05	6.61E-01	1.40E+00

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 800005302)
• [2] Clinical pharmacokinetics and pharmacodynamics of a new squalene synthase inhibitor, BMS-188494, in healthy volunteers. J Clin Pharmacol. 1998 Dec;38(12):1116-21.
• [3] Site-selective enzymatic labeling of designed ankyrin repeat proteins using protein farnesyltransferase. Methods Mol Biol. 2019;2033:207-219.
• [4] Increased activity of the sterol branch of the mevalonate pathway elevates glycosylation of secretory proteins and improves antifungal properties of Trichoderma atroviride. Fungal Genet Biol. 2020 Jan 17;137:103334.
• [5] Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous le... Br J Pharmacol. 2008 Jul;154(5):949-57.
• [6] Phosphonosulfonates are potent, selective inhibitors of dehydrosqualene synthase and staphyloxanthin biosynthesis in Staphylococcus aureus. J Med Chem. 2009 Feb 26;52(4):976-88.
• [7] Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo. J Biol Chem. 1992 Jun 15;267(17):11705-8.
• [8] (1 alpha, 2 beta, 3 beta, 4 alpha)-1,2-bis[N-propyl-N-(4-phenoxybenzyl) amino]carbonyl]cyclobutane-3,4-dicarboxylic acid (A-87049): a novel potent ... J Med Chem. 1997 Jul 4;40(14):2123-5.
• [9] RPR 101821, a new potent cholesterol-lowering agent: inhibition of squalene synthase and 7-dehydrocholesterol reductase. Naunyn Schmiedebergs Arch Pharmacol. 1996 Jan;353(2):233-40.
• [10] Inhibition of farnesyl protein transferase by new farnesyl phosphonate derivatives of phenylalanine, Bioorg. Med. Chem. Lett. 6(12):1291-1296 (1996).
• [11] Structure-activity relationships of C1 and C6 side chains of zaragozic acid A derivatives. J Med Chem. 1994 Nov 11;37(23):4031-51.
• [12] Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation. Bioorg Med Chem Lett. 1998 Apr 21;8(8):891-6.
• [13] Inhibition of staphyloxanthin virulence factor biosynthesis in Staphylococcus aureus: in vitro, in vivo, and crystallographic results. J Med Chem. 2009 Jul 9;52(13):3869-80.