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

General Information of Drug (ID: DMSIVND)

• Drug Name: Hydroxychloroquine Drug Info
• Synonyms: Hidroxicloroquina; Hidroxicloroquina [INN-Spanish]; Hydroxychlorochin; Gen-Hydroxychloroquine 200mg Tablets; HCQ; Hydroxychloroguine; Hydroxychloroquine (INN);Hydroxychloroquine [INN:BAN]; Hydroxychloroquine Sulfate (1:1) Salt; Hydroxychloroquinum; Hydroxychloroquinum [INN-Latin]; Idrossiclorochina; Idrossiclorochina [DCIT]; Oxichlorochinum; Oxichloroquine; Oxychlorochin; Oxychloroquine; Plaquenil (TN); Polirreumin; Polirreumin (TN); Quensyl; WIN 1258

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1] , [2]

• Therapeutic Class: Antimalarials
• Cross-matching ID:
  PubChem CID: 3652
  ChEBI ID: CHEBI:5801
  CAS Number: CAS 118-42-3
  TTD Drug ID: DMSIVND
  VARIDT Drug ID: DR00449
  INTEDE Drug ID: DR0837
  ACDINA Drug ID: D00316

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[9]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[14]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[15]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[16]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[17]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[18]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[19]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[20]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

Drug(s) Targeting Toll-like receptor 7 (TLR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imiquimod	DM1TMA3	Skin cancer	2C30-2C37	Approved	[24]
ANA773	DMSC8YW	Hepatitis C virus infection	1E51.1	Phase 2a	[25]
GS-9620	DMG5C8D	Hepatitis B virus infection	1E51.0	Phase 2	[26]
IMO-3100	DMM549D	Psoriasis vulgaris	EA90	Phase 2	[27]
Resiquimod	DML6XSP	Actinic keratosis	EK90.0	Phase 2	[28]
LOXORIBINE	DMIV9ZE	Immune System disease	4A01-4B41	Phase 2	[29]
GSK2245035	DMBWPZJ	Asthma	CA23	Phase 2	[30]
AZD-8848	DM0M7QW	Allergic rhinitis	CA08.0	Phase 2	[31]
Isatoribine	DMHOJ8W	Hepatitis C virus infection	1E51.1	Phase 2	[32]
PF-4878691	DM24I0N	Melanoma	2C30	Phase 2	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Antagonist	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

References

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• [5] Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
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• [11] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [12] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [13] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [14] 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.
• [15] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [16] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [17] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [18] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [19] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [20] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [21] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [22] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [23] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [24] Imiquimod enhances IFN-gamma production and effector function of T cells infiltrating human squamous cell carcinomas of the skin. J Invest Dermatol. 2009 Nov;129(11):2676-85.
• [25] Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
• [26] Pharmacokinetic and pharmacodynamic properties of GS-9620, a novel Toll-like receptor 7 agonist, demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses. J Pharmacol Exp Ther. 2014 Jan;348(1):96-105.
• [27] Company report (Iderapharma)
• [28] TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).Vaccine.2005 Nov 1;23(45):5263-70.
• [29] The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur J Immunol. 2003 Nov;33(11):2987-97.
• [30] Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement. Clin Pharmacol Ther. 2015 Oct;98(4):369-80.
• [31] Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res. 2012 Jun 22;13:53.
• [32] Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine. Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):635-40.
• [33] The innate immune response, clinical outcomes, and ex vivo HCV antiviral efficacy of a TLR7 agonist (PF-4878691). Clin Pharmacol Ther. 2011 Jun;89(6):821-9.