Details of the Drug

General Information of Drug (ID: DMWK9BX)

• Drug Name: SQ-109
• Synonyms: SQ-37; SQ-59; Antibiotics (tuberculosis), Sequella; Second-generation EMB, Sequella; Second-generation ethambutol, Sequella

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Phase 2	[1], [2]
Tuberculosis	1B10-1B1Z	Phase 2	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 330.5
  Topological Polar Surface Area (xlogp); 5.1
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C22H38N2
  IUPAC Name: N'-(2-adamantyl)-N-[(2E)-3,7-dimethylocta-2,6-dienyl]ethane-1,2-diamine
  Canonical SMILES: CC(=CCC/C(=C/CNCCNC1C2CC3CC(C2)CC1C3)/C)C
  InChI: InChI=1S/C22H38N2/c1-16(2)5-4-6-17(3)7-8-23-9-10-24-22-20-12-18-11-19(14-20)15-21(22)13-18/h5,7,18-24H,4,6,8-15H2,1-3H3/b17-7+
  InChIKey: JFIBVDBTCDTBRH-REZTVBANSA-N
• Cross-matching ID:
  PubChem CID: 5274428
  CAS Number: 502487-67-4
  DrugBank ID: DB05186
  TTD ID: D0K8DI
  INTEDE ID: DR1852

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mycobacterium Membrane protein mmpL3 (MycB mmpL3)	TTTLB3R	MMPL3_MYCTU	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[5]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[5]

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: 7997).
• [2] ClinicalTrials.gov (NCT01218217) Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2012 Apr;56(4):1797-809.
• [5] Interspecies pharmacokinetics and in vitro metabolism of SQ109. Br J Pharmacol. 2006 Mar;147(5):476-85.
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• [14] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [15] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [16] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [17] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [18] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [19] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [20] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [21] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [22] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [23] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [24] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [25] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [26] MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob Agents Chemother. 2012 Jan;56(1):324-31.