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

General Information of Drug (ID: DMWK9BX)

• Drug Name: SQ-109 Drug Info
• 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]
Tuberculosis	1B10-1B1Z	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 5274428
  CAS Number: CAS 502487-67-4
  TTD Drug ID: DMWK9BX
  INTEDE Drug ID: DR1852

Molecule-Related Drug Atlas

Drug(s) Targeting Mycobacterium Membrane protein mmpL3 (MycB mmpL3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BM-212	DMIRX3Z	Asthma	CA23	Phase 1	[5]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[9]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[11]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[12]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[13]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[14]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[15]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[17]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[24]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[25]

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	[3]

Drug-Metabolizing Enzyme (DME)

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

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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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.
• [4] Interspecies pharmacokinetics and in vitro metabolism of SQ109. Br J Pharmacol. 2006 Mar;147(5):476-85.
• [5] MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob Agents Chemother. 2012 Jan;56(1):324-31.
• [6] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [7] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [8] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [11] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [12] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [13] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [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.