BRINCIDOFOVIR

First approved in 1996

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H52N3O7P
Molecular Weight	561.6914
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCCCCCCCCCCCOCCCOP(O)(=O)CO[C@H](CO)CN1C=CC(N)=NC1=O

InChI

InChIKey=WXJFKKQWPMNTIM-VWLOTQADSA-N

InChI=1S/C27H52N3O7P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19-35-20-16-21-37-38(33,34)24-36-25(23-31)22-30-18-17-26(28)29-27(30)32/h17-18,25,31H,2-16,19-24H2,1H3,(H,33,34)(H2,28,29,32)/t25-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10473024 | https://www.ncbi.nlm.nih.gov/pubmed/8630098

Cidofovir is an antiviral nucleotide analogue with significant activity against cytomegalovirus (CMV) and other herpesviruses. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human herpesvirus 5 DNA polymerase 18 Target ID: CHEMBL3414 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8630098	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus retinitis 16 Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf	Primary		Approved 8429	VISTIDE Approved Use Cidofovir injection is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS). Launch Date 1996

C_max

Value	Dose	Analyte	Population
7.34 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.12 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
19.96 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.34 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.35 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	3 mg/kg 1 times / week other, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	5 mg/kg 1 times / week other, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7574510	1 mg/kg 1 times / week other, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CIDOFOVIR serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 % single, topical Highest studied dose Dose: 5 % Route: topical Route: single Dose: 5 % Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	unhealthy, 21–66 n = 96 Health Status: unhealthy Condition: Recurrent genital herpes Age Group: 21–66 Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	Disc. AE: Ulceration... AEs leading to discontinuation/dose reduction: Ulceration (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998
10 mg/kg single, intravenous Highest studied dose Dose: 10 mg/kg Route: intravenous Route: single Dose: 10 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	unhealthy n = 5 Health Status: unhealthy Condition: Acquired immunodeficiency syndrome (AIDS) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154
10 mg/kg single, oral Highest studied dose Dose: 10 mg/kg Route: oral Route: single Dose: 10 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	unhealthy n = 5 Health Status: unhealthy Condition: Acquired immunodeficiency syndrome (AIDS) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154	Sources: https://pubmed.ncbi.nlm.nih.gov/8739595 Page: p.154
5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	Disc. AE: Acute renal failure... Other AEs: Renal impairment, Neutropenia... AEs leading to discontinuation/dose reduction: Acute renal failure Other AEs: Renal impairment Neutropenia Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1

AEs

AE	Significance	Dose	Population
Ulceration	2% Disc. AE	5 % single, topical Highest studied dose Dose: 5 % Route: topical Route: single Dose: 5 % Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998	unhealthy, 21–66 n = 96 Health Status: unhealthy Condition: Recurrent genital herpes Age Group: 21–66 Sex: M+F Population Size: 96 Sources: https://pubmed.ncbi.nlm.nih.gov/9797239 Page: p.2998
Neutropenia		5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1
Renal impairment		5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1
Acute renal failure	Disc. AE	5 mg/kg 1 times / week multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / week Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / week Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1	unhealthy Health Status: unhealthy Condition: CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=90639fc6-0295-4115-98f0-054b783850ce&type=display Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OAT1 326 OAT3 339 OCT2 355

Drug as victim

Target	Modality	Activity
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3696	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3696
ChemicalBook	CB01178278	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01178278
ChemicalBook	CB5492709	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5492709
Selleck Chemicals	Cidofovir	http://www.selleckchem.com/products/Cidofovir.html
ZINC	ZINC000001530600	http://zinc15.docking.org/substances/ZINC000001530600
eMolecules	2729368	https://www.emolecules.com/cgi-bin/more?vid=2729368

PubMed

Title	Date	PubMed
Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells.	2000	11697818
Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation.	2001	11529489
Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.	2001	11465299
Cidofovir in the treatment of HPV-associated lesions.	2001	11436421
Successful treatment of severe respiratory papillomatosis with intravenous cidofovir and interferon alpha-2b.	2001 Apr	11401080
Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs.	2001 Apr-Jul	11563082
An efficient process for the synthesis of cyclic HPMPC.	2001 Apr-Jul	11562964
Cytomegalovirus treatment options in immunocompromised patients.	2001 Aug	11584992
Infections after stem cell transplantation in children: state of the art and recommendations.	2001 Aug	11571529
Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: a monocenter observational study with clinical and JC virus load monitoring.	2001 Aug	11517420
The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy.	2001 Aug	11517417
Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination.	2001 Aug	11485181
Acute renal failure in a lung transplant patient after therapy with cidofovir.	2001 Dec	11793044
Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action.	2001 Dec	11733458
Antiviral activity of NMSO3 against adenovirus in vitro.	2001 Dec	11675145
Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model.	2001 Dec	11675144
Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.	2001 Dec 1	11719390
Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy.	2001 Feb	11487186
Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir.	2001 Jan	11437324
The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand White rabbit ocular model.	2001 Jul	11431446
Use of cidofovir in progressive multifocal leukoencephalopathy.	2001 Jun	11408993
Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons.	2001 Jun	11403192
Progress in understanding cytomegalovirus drug resistance.	2001 Jun	11397658
[Oncogenic human papillomaviruses in extra-genital Bowen disease revealed by in situ hybridization].	2001 Jun-Jul	11460032
Cidofovir.	2001 Mar	11682777
[Anterior uveitis and cidofovir].	2001 May	11397985
Successful treatment of aids related PML with HAART and cidofovir.	2001 May 29	11410399
Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology.	2001 May-Jun	11419030
Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.	2001 Nov	11781649
Successful treatment of foscarnet-resistant herpes simplex stomatitis with intravenous cidofovir in a child.	2001 Nov	11734717
Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy.	2001 Nov	11702907
Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo.	2001 Nov	11602788
Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule.	2001 Nov	11602668
Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs.	2001 Nov 1	11691806
Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.	2001 Nov 1	11577375
Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8.	2001 Nov-Dec	11747000
Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient.	2001 Oct	11781635
Cidofovir for KS lesions.	2001 Oct	11768871
Progressive multifocal leukoencephalopathy in a child with hyperimmunoglobulin E recurrent infection syndrome and review of the literature.	2001 Oct	11748496
Cytomegalovirus infection: the point in 2001.	2001 Oct	11737406
[Prospects for therapy and prevention of adenovirus keratoconjunctivitis].	2001 Oct	11699326
Anti-CD20 monoclonal antibody (Rituximab) and Cidofovir as successful treatment of an EBV-associated lymphoma with CNS involvement.	2001 Oct	11694778
A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA maturation via the UL89 and UL56 gene products.	2001 Oct	11533171
Bioterrorism. Blocking smallpox: a second defense.	2001 Oct 19	11641477
Treatment of a bowenoid papulosis of the penis with local applications of cidofovir in a patient with acquired immunodeficiency syndrome.	2001 Oct 22	11606156
Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 Sep	11642018
Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein.	2001 Sep	11505446
Strategies for management of cytomegalovirus (CMV) infection after allogeneic bone marrow transplantation: the "doubling of baseline CMV pp65 antigenemia" and the "cidofovir as rescue treatment approaches.	2001 Sep 1	11547769
Combined surgical-medical treatment of genital warts in HIV positive patients.	2001 Sep-Oct	11765191
Cidofovir-induced end-stage renal failure.	2002 Jan	11773481

Patents

Sample Use Guides

In Vivo Use Guide

Induction Treatment The recommended induction dose of VISTIDE (cidofovir injection) for patients with a serum creatinine of ≤1.5 mg/dL, a calculated creatinine clearance >55 mL/min, and a urine protein <100 mg/dL (equivalent to <2+ proteinuria) is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once weekly for two consecutive weeks. Maintenance Treatment The recommended maintenance dose of VISTIDE is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr), administered once every 2 weeks.

Route of Administration: Intravenous

In Vitro Use Guide

Cidofovir is active in vitro against a variety of laboratory and clinical isolates of cytomegalovirus with IC50 values of 0.5-2.8 uM (WT isolates)

Name

Type

Language

BRINCIDOFOVIR

Official Name

English

BRINCIDOFOVIR [USAN]

Common Name

English

TEMBEXA

Brand Name

English

HDP-CIDOFOVIR

Common Name

English

Brincidofovir [WHO-DD]

Common Name

English

BRINCIDOFOVIR [ORANGE BOOK]

Common Name

English

HEXADECYLOXYPROPYL CIDOFOVIR

Common Name

English

HEXADECYLOXYPROPYL-CIDOFOVIR

Common Name

English

brincidofovir [INN]

Common Name

English

CMX001

Code

English

PHOSPHONIC ACID, P-(((1S)-2-(4-AMINO-2-OXO-1(2H)-PYRIMIDINYL)-1-(HYDROXYMETHYL)ETHOXY)METHYL)-, MONO(3-(HEXADECYLOXY)PROPYL) ESTER

Common Name

English

CMX-001

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/16/1644