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

General Information of Drug (ID: DM24I0N)

• Drug Name: PF-4878691 Drug Info
• Synonyms: PF-04878691; PF-4171455

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Phase 2	[1]
Hepatitis C virus infection	1E51.1	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 10309114
  CAS Number: CAS 532959-63-0
  TTD Drug ID: DM24I0N

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	[5]
Hydroxychloroquine	DMSIVND	Chronic renal failure	GB61.Z	Approved	[6]
ANA773	DMSC8YW	Hepatitis C virus infection	1E51.1	Phase 2a	[7]
GS-9620	DMG5C8D	Hepatitis B virus infection	1E51.0	Phase 2	[8]
IMO-3100	DMM549D	Psoriasis vulgaris	EA90	Phase 2	[9]
Resiquimod	DML6XSP	Actinic keratosis	EK90.0	Phase 2	[10]
LOXORIBINE	DMIV9ZE	Immune System disease	4A01-4B41	Phase 2	[11]
GSK2245035	DMBWPZJ	Asthma	CA23	Phase 2	[12]
AZD-8848	DM0M7QW	Allergic rhinitis	CA08.0	Phase 2	[13]
Isatoribine	DMHOJ8W	Hepatitis C virus infection	1E51.1	Phase 2	[14]

Drug(s) Affected By Toll-like receptor 8 (TLR8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Chloroquine	DMSI5CB	Malaria	1F40-1F45	Approved	[16]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[17]
Malathion	DMXZ84M	Pediculus capitis infestation	1G00.0	Approved	[18]
Nabiximols	DMHKJ5I	Cancer related pain	MG30	Phase 3	[19]

Drug(s) Affected By Programmed cell death 1 ligand 1 (CD274)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[21]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[22]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[23]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[24]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[26]
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]

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	Agonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Programmed cell death 1 ligand 1 (CD274)	OTJ0VFDL	PD1L1_HUMAN	Gene/Protein Processing	[4]
Toll-like receptor 8 (TLR8)	OTEJRL9C	TLR8_HUMAN	Gene/Protein Processing	[4]

References

• [1] ClinicalTrials.gov (NCT00189332) Use of 852A in Metastatic Cutaneous Melanoma.. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT00810758) Multiple Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-04878691. U.S. National Institutes of Health.
• [3] 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.
• [4] Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. Antimicrob Agents Chemother. 2010 Feb;54(2):871-81. doi: 10.1128/AAC.01246-09. Epub 2009 Nov 30.
• [5] 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.
• [6] TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
• [7] Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
• [8] 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.
• [9] Company report (Iderapharma)
• [10] TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).Vaccine.2005 Nov 1;23(45):5263-70.
• [11] 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.
• [12] 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.
• [13] Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res. 2012 Jun 22;13:53.
• [14] Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine. Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):635-40.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. Sci Rep. 2016 Jul 7;6:29447. doi: 10.1038/srep29447.
• [17] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [18] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [19] Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
• [20] Oxidative stress modulates expression of immune checkpoint genes via activation of AhR signaling. Toxicol Appl Pharmacol. 2022 Dec 15;457:116314. doi: 10.1016/j.taap.2022.116314. Epub 2022 Nov 9.
• [21] Essential role of HDAC6 in the regulation of PD-L1 in?melanoma. Mol Oncol. 2016 May;10(5):735-750. doi: 10.1016/j.molonc.2015.12.012. Epub 2016 Jan 6.
• [22] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [23] Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis-mediated VEGFA expression and PD-1/PD-L1 checkpoint in NSCLC. Chem Biol Interact. 2021 Nov 1;349:109652. doi: 10.1016/j.cbi.2021.109652. Epub 2021 Sep 11.
• [24] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [25] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [26] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [27] CircRNA VIM silence synergizes with sevoflurane to inhibit immune escape and multiple oncogenic activities of esophageal cancer by simultaneously regulating miR-124/PD-L1 axis. Cell Biol Toxicol. 2022 Oct;38(5):825-845. doi: 10.1007/s10565-021-09613-0. Epub 2021 May 20.
• [28] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.