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

General Information of Drug (ID: DMOUMDV)

• Drug Name: Penciclovir Drug Info
• Synonyms: penciclovir; 39809-25-1; Denavir; Penciclovirum; Vectavir; Penciclovirum [INN-Latin]; Pencyclovir; BRL-39123; BRL 39123; Penciclovir [USAN:INN:BAN]; Penciceovir; UNII-359HUE8FJC; CCRIS 9213; PE2

Indication

Disease Entry	ICD 11	Status	REF
Herpes simplex labialis	1F00.01	Approved	[1]
Human immunodeficiency virus infection	1C62	Approved	[2]
Meniere disease	AB31.0	Approved	[1]
Recurrent herpes labialis	1F00.01	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]

• Therapeutic Class: Antiviral Agents
• Cross-matching ID:
  PubChem CID: 135398748
  ChEBI ID: CHEBI:7956
  CAS Number: CAS 39809-25-1
  TTD Drug ID: DMOUMDV
  VARIDT Drug ID: DR01263

Molecule-Related Drug Atlas

Drug(s) Targeting Thymidine kinase 1 (TK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DEOXYCYTIDINE	DMYE5LJ	Acute myeloid leukaemia	2A60	Approved	[8]
TK-DLI	DM26I8H	Graft-versus-host disease	4B24	Preregistration	[9]
FV-100	DMZARP1	Varicella zoster virus infection	1E91	Phase 3	[10]
Radiosensitizer gene therapy	DMN1ZEU	Pancreatic cancer	2C10	Phase 3	[11]
RP101	DMNIYSZ	Infectious disease	1A00-CA43.1	Phase 2/3	[12]
HQK-1004	DM3WX0K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
Rilapladib	DMB9861	Arteriosclerosis	BD40	Phase 1	[14]
Ad-OC-hsvTK/valacyclovir	DM9GLHO	Prostate cancer	2C82.0	Phase 1	[15]
Thymidine kinase-expressing adenovirus and ganciclovir suicide gene therapy	DMO8SGD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
Sitimagene ceradenovec	DM0T2QV	Brain cancer	2A00	Discontinued in Phase 3	[17]

Drug(s) Targeting Herpes simplex virus DNA polymerase UL30 (HSV UL30)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[19]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[20]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[21]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[19]
Valganciclovir	DMS2IUH	Virus infection	1A24-1D9Z	Approved	[22]
Famciclovir	DMJHLSD	Meniere disease	AB31.0	Approved	[23]
Valacyclovir Hydrochloride	DM5I1CE	Herpes simplex virus infection	1F00	Approved	[19]
Foscavir	DM9KJLZ	Cytomegalovirus retinitis	9B72.00	Approved	[22]
Netivudine	DMTKRY1	Virus infection	1A24-1D9Z	Phase 3	[24]

Drug(s) Targeting COVID-19 RNA-directed RNA polymerase (RdRp)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Remdesivir	DMBFZ6L	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[4]
Remdesivir	DMBFZ6L	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[25]
Anidulafungin	DM8QM5U	Aspergillosis	1F20	Approved	[26]
Favipiravir	DMBZ27L	Influenza virus infection	1E30-1E32	Registered	[27]
Galidesivir	DMG9C4I	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1 Trial	[28]
Suramin	DMTOUY9	African trypanosomiasis	1F51	Phase 1	[26]

Drug(s) Transported By Organic anion transporter 2 (SLC22A7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[30]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[31]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[32]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[33]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[34]
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[35]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[36]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[37]
Theophylline	DMRJFN9	Bronchitis	CA20	Approved	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30)	TTIU7X1	DPOL_HHV11	Inhibitor	[5]
Thymidine kinase 1 (TK1)	TTP3QRF	KITH_HUMAN	Inhibitor	[6]
COVID-19 RNA-directed RNA polymerase (RdRp)	TTV1095	R1AB_SARS2 (4393-5324)	Inhibitor	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[7]

References

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• [4] Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
• [5] Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] In vitro studies with two human organic anion transporters: OAT2 and OAT7. Xenobiotica. 2018 Oct;48(10):1037-1049.
• [8] Species- or isozyme-specific enzyme inhibitors. 5. Differential effects of thymidine substituents on affinity for rat thymidine kinase isozymes. J Med Chem. 1982 Jun;25(6):644-9.
• [9] Company report (Takara Bio)
• [10] Specific recognition of the bicyclic pyrimidine nucleoside analogs, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase. Mol Pharmacol. 2002 Feb;61(2):249-54.
• [11] Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy. Clin Cancer Res. 1997 Nov;3(11):2081-8.
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• [13] Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001 Sep;13(5):360-7.
• [14] Trichomonas vaginalis thymidine kinase: purification, characterization and search for inhibitors. Biochem J. 1998 Aug 15;334 ( Pt 1):15-22.
• [15] Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther. 2003 Feb 10;14(3):227-41.
• [16] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [17] Sitimagene ceradenovec: a gene-based drug for the treatment of operable high-grade glioma. Future Oncol. 2010 Nov;6(11):1691-710.
• [18] Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [20] Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009 Feb;30(2):77-81.
• [21] Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient. Oral Microbiol Immunol. 2009 Apr;24(2):109-15.
• [22] Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22.
• [23] Penciclovir cream--improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8.
• [24] Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment. Drugs. 1999 Feb;57(2):187-206.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [26] Suramin, Penciclovir and Anidulafungin bind nsp12, which governs the RNA-dependent-RNA polymerase activity of SARS-CoV-2, with higher interaction energy than Remdesivir, indicating potential in the treatment of Covid-19 infection. April.21.2020. Doi: 10.31219/osf.io/urxwh
• [27] Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. medRxiv. Posted April 15, 2020.
• [28] BioCryst Begins Clinical Trial with Galidesivir for Treatment of Patients with COVID-19
• [29] Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
• [30] Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
• [31] Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
• [32] Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
• [33] Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22.
• [34] Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82.
• [35] Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008 Apr;73(4):1151-8.
• [36] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [37] Human organic anion transporter 2 is an entecavir, but not tenofovir, transporter. Drug Metab Pharmacokinet. 2017 Feb;32(1):116-119.