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

General Information of Drug (ID: DMG5C8D)

• Drug Name: GS-9620 Drug Info
• Synonyms: GS-9620; 1228585-88-3; Vesatolimod; GS9620; UNII-O8M467C50G; GS 9620; CHEMBL2424780; O8M467C50G; 8-(3-(pyrrolidin-1-ylmethyl)benzyl)-4-amino-2-butoxy-7,8-dihydropteridin-6(5H)-one; 4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one; 4-Amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one; 4-azanyl-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one; Vesatolimod [INN]; Vesatolimod [USAN:INN]; Vesatolimod (USAN/INN); SCHEMBL10083191

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis B virus infection	1E51.0	Phase 2	[1]
Human immunodeficiency virus infection	1C62	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 46241268
  CAS Number: CAS 1228585-88-3
  TTD Drug ID: DMG5C8D
  INTEDE Drug ID: DR1834

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[4]
Hydroxychloroquine	DMSIVND	Chronic renal failure	GB61.Z	Approved	[5]
ANA773	DMSC8YW	Hepatitis C virus infection	1E51.1	Phase 2a	[6]
IMO-3100	DMM549D	Psoriasis vulgaris	EA90	Phase 2	[7]
Resiquimod	DML6XSP	Actinic keratosis	EK90.0	Phase 2	[8]
LOXORIBINE	DMIV9ZE	Immune System disease	4A01-4B41	Phase 2	[9]
GSK2245035	DMBWPZJ	Asthma	CA23	Phase 2	[10]
AZD-8848	DM0M7QW	Allergic rhinitis	CA08.0	Phase 2	[11]
Isatoribine	DMHOJ8W	Hepatitis C virus infection	1E51.1	Phase 2	[12]
PF-4878691	DM24I0N	Melanoma	2C30	Phase 2	[13]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

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	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

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

References

• [1] 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.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection. J Hepatol. 2015 Aug;63(2):320-8.
• [4] 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.
• [5] TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
• [6] Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
• [7] Company report (Iderapharma)
• [8] TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).Vaccine.2005 Nov 1;23(45):5263-70.
• [9] 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.
• [10] 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.
• [11] Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res. 2012 Jun 22;13:53.
• [12] Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine. Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):635-40.
• [13] 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.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] 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.
• [19] 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.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] 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.
• [22] 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.