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

General Information of Drug (ID: DM4JZPT)

• Drug Name: Squalestatin 1 Drug Info
• Synonyms: Zaragozic acid A; squalestatin 1; Squalestatin; 142561-96-4; ZARAGOZIC ACIDS A; UNII-1117HVX02L; CHEMBL280978; CHEBI:75170; 1117HVX02L; 1S-((4S-acetoxy-5R-methyl-3-methylene-6-phenylhexyl)-6-(E)-4S,6S-dimethyloct-2-enoyloxy)-4,7S-dihydroxy-2,8-dioxabicyclo[321]octane-3S,4S,5R-tricarboxylic acid; L-erythro-L-glycero-D-altro-7-Trideculo-7,4-furanosonic acid, 2,7-anhydro-3,4-di-C-carboxy-8,9,10,12,13-pentadeoxy-10-methylene-12-(phenylmethyl)-, 11-acetate 5-(4,6-dimethyl-2-octenoate), (5(2E,4S,6S),7S)-; Squalestatin 1, Glaxo; Zaragozic acid A, Glaxo

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 6438355
  ChEBI ID: CHEBI:75170
  CAS Number: CAS 142561-96-4
  TTD Drug ID: DM4JZPT

Molecule-Related Drug Atlas

Drug(s) Targeting RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[4]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[4]
GDC-0068	DMWBZJD	Breast cancer	2C60-2C65	Phase 3	[4]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[5]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[6]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[7]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[8]
RX-0201	DMTBAV3	Pancreatic cancer	2C10	Phase 2	[9]
PTX-200	DM0ZIT2	Breast cancer	2C60-2C65	Phase 2	[4]
Triciribine prodrug	DMBN1XS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]

Drug(s) Targeting Squalene synthetase (FDFT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lapaquistat acetate	DMJY9CW	Hyperlipidaemia	5C80	Discontinued in Phase 3	[10]
SQ-32709	DMSQRXW	Arteriosclerosis	BD40	Discontinued in Phase 2	[11]
BMS-187745	DMP8SIV	Hyperlipidaemia	5C80	Discontinued in Phase 2	[12]
A-87049	DMUID46	N. A.	N. A.	Terminated	[13]
RPR-101821	DM21Y75	Arteriosclerosis	BD40	Terminated	[14]
SQ-34919	DMT7O9V	N. A.	N. A.	Terminated	[15]
L-735021	DM8BVJQ	Discovery agent	N.A.	Investigative	[16]
PMID19191557C32	DMH8QRI	Discovery agent	N.A.	Investigative	[12]
PMID9871507C14	DMY28QM	Discovery agent	N.A.	Investigative	[17]
PMID19456099C13	DMBU9E4	Discovery agent	N.A.	Investigative	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[2]
Squalene synthetase (FDFT1)	TTFQEO5	FDFT_HUMAN	Modulator	[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: 3057).
• [2] Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol. 2008 Sep;4(9):538-47.
• [3] Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo. J Biol Chem. 1992 Jun 15;267(17):11705-8.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [6] Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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. (Target id: 1479).
• [9] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [10] 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.
• [11] Clinical pharmacokinetics and pharmacodynamics of a new squalene synthase inhibitor, BMS-188494, in healthy volunteers. J Clin Pharmacol. 1998 Dec;38(12):1116-21.
• [12] Phosphonosulfonates are potent, selective inhibitors of dehydrosqualene synthase and staphyloxanthin biosynthesis in Staphylococcus aureus. J Med Chem. 2009 Feb 26;52(4):976-88.
• [13] (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.
• [14] 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.
• [15] Inhibition of farnesyl protein transferase by new farnesyl phosphonate derivatives of phenylalanine, Bioorg. Med. Chem. Lett. 6(12):1291-1296 (1996).
• [16] Structure-activity relationships of C1 and C6 side chains of zaragozic acid A derivatives. J Med Chem. 1994 Nov 11;37(23):4031-51.
• [17] Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation. Bioorg Med Chem Lett. 1998 Apr 21;8(8):891-6.
• [18] 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.