BRINCIDOFOVIR

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

Molecular Formula	C27H52N3O7P
Molecular Weight	561.6914
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 17 Target ID: CHEMBL3414 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8630098	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cytomegalovirus retinitis 15 Sources: http://www.gilead.com/~/media/files/pdfs/medicines/other/vistide/vistide.pdf	Primary		Approved 8360	VISTIDE Approved Use Cidofovir injection is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS). Launch Date 8.3574718E11

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 320 OAT3 333 OCT2 348

Drug as victim

Target	Modality	Activity
OCT2 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	no
OAT1 320	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17372702/ Page: -	yes
OAT3 333	substrate 3326 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

The cyclohexene ring system as a furanose mimic: synthesis and antiviral activity of both enantiomers of cyclohexenylguanine.	2000 Feb 24	10691698
Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections.	2001 Apr	11292644
Potent inhibition of hemangiosarcoma development in mice by cidofovir.	2001 Apr 15	11291040
Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs.	2001 Apr-Jul	11563082
Acute renal failure in a lung transplant patient after therapy with cidofovir.	2001 Dec	11793044
Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir.	2001 Jan	11437324
Diagnostic and therapeutic dilemmas of a large scrotal lesion in an AIDS patient.	2001 Jan	11215088
The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand White rabbit ocular model.	2001 Jul	11431446
Progress in understanding cytomegalovirus drug resistance.	2001 Jun	11397658
[Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection].	2001 Jun-Jul	11460038
Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.	2001 Mar	11429040
Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 May 1	11303263
Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.	2001 Nov	11781649
Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.	2001 Nov 1	11577375
Cidofovir for KS lesions.	2001 Oct	11768871
Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine: a controlled clinical pilot study.	2001 Oct	11594949
Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection.	2001 Sep 1	11477525
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)

Substance Class	Chemical Created by `admin` on `Thu Jul 06 04:28:05 UTC 2023` Edited by `admin` on `Thu Jul 06 04:28:05 UTC 2023`
Record UNII	6794O900AX
Record Status	`Validated (UNII)`
Record Version

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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