BROXURIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H11BrN2O5
Molecular Weight	307.098
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(Br)C(=O)NC2=O

InChI

InChIKey=WOVKYSAHUYNSMH-RRKCRQDMSA-N

InChI=1S/C9H11BrN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1

HIDE SMILES / InChI

Description
Sources: DOI: 10.1007/BF02906709
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/17704656 http://download.springer.com/static/pdf/342/art%253A10.1007%252Fs11240-006-9126-y.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs11240-006-9126-y&token2=exp=1473497643~acl=%2Fstatic%2Fpdf%2F342%2Fart%25253A10.1007%25252Fs11240-006-9126-y.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs11240-006-9126-y*~hmac=528d87254b1304d1a2f0adf99a8d34af0617e18c12659e3355277326ee2a8ea7

Broxuridine (5-Bromo-2-deoxyuridine, BrdU) is a thymidine analogue that is incorporated into replicating DNA. BrdU taken up by cells is phosphorylated and incorporated into DNA in place of dT. Although originally designed as a chemotherapeutic agent, sublethal concentrations of BrdU have long been known to alter the growth and phenotype of a wide range of cell types. The most popular use of BrdU is as a tracer of DNA synthesis. The other well-known use of BrdU is as a DNA photosensitizer. BrdU substitution of dT in DNA sensitizes it to near-UV light, and cells with BrdU-substituted DNA cannot survive after exposure to near-UV light. BUdR has side effects on cell functions. Cell growth can be inhibited, normal development of differentiating systems be perturbed, activities of specific enzymes be reduced. Mutagenic effects of BUdR are interpreted as reflections of a mispairing of BUdR in its rare enol form. Effects of BUdR which can be reversed by addition of thymidine are not likely to be mutagenic. As another mechanism of action of BUdR has been suggested that incorporation of BUdR into DNA alters the pattern of transcription.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
base conversion or substitution editing 1 Target ID: GO:0016553 Sources: DOI: 10.1007/BF02906709	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: https://clinicaltrials.gov/ct2/show/NCT00003832	Diagnostic	Phase II 1132	Unknown Approved Use Unknown
Acute myelogenous leukemia 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00003405	Primary	Phase II 1132	Unknown Approved Use Unknown
Hematologic malignancies 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00042250	Diagnostic	Phase II 1132	Unknown Approved Use Unknown
Brain cancer 10 Sources: https://adisinsight.springer.com/drugs/800009236	Primary	Phase III 656	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://adisinsight.springer.com/drugs/800009236	Diagnostic	Phase III 656	Unknown Approved Use Unknown
HIV-1 infection 151 Sources: https://clinicaltrials.gov/ct2/show/NCT00001650	Secondary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Nucleosides. 3. Studies on 5-methylamino-2'-deoxyuridine as a specific antiherpes agent.	1966 May	5960908
The effects of 5-bromodeoxyuridine on fusion of the cranial neural folds in the mouse embryo.	1985 Oct	4049281
Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo.	2002 Jun 14	12044546
Endogenous production of heparin-binding EGF-like growth factor during murine partial-thickness burn wound healing.	2002 Mar-Apr	11882801
Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans.	2003 Aug 4	12898625
Design of Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors.	2003 May-Aug	14565282
Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor.	2003 Oct	14563798
An immunohistochemical study of the expression of heat-shock protein-25 and cell proliferation in the dental pulp and enamel organ during odontogenesis in rat molars.	2006 May	16259940
Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat.	2007	17473396
Loss of input from the mossy cells blocks maturation of newly generated granule cells.	2007	17455193
Downregulation of hnRNP C1/C2 by siRNA sensitizes HeLa cells to various stresses.	2007 Feb	16960656
NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice.	2007 Jun	17401437
Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle.	2007 May 11	17413043
The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts.	2007 Nov 2	17980035
High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation.	2008 Oct	18614613
Apoptotic cell death, long-term persistence, and neuronal differentiation of aneuploid cells generated in the adult brain of teleost fish.	2008 Sep 1	18563701
VILIP-1 expression in vivo results in decreased mouse skin keratinocyte proliferation and tumor development.	2010 Apr 15	20419170
Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8.	2010 Feb 22	20170548
In the absence of Sonic hedgehog, p53 induces apoptosis and inhibits retinal cell proliferation, cell-cycle exit and differentiation in zebrafish.	2010 Oct 21	21042410
Acyclic retinoid NIK-333 accelerates liver regeneration and lowers serum transaminase activities in 70% partially hepatectomized rats, in vivo.	2010 Sep 25	20619257

Patents

Sample Use Guides

In Vivo Use Guide

Broxuridine (BrdUrd) was infused via the arterial catheter for 7 days at a dose rate of 25 mg/kg/day

Route of Administration: Intra-arterial

In Vitro Use Guide

Tritiated Broxuridine (BrdUrd) was used to estab lish the extent of variation between 3 glioblastoma cell lines (U-251, U-118, and D-54). Imax is the maximum amount of BrdUrd incorporation after one cell doubling and C50 is the BrdUrd concentration required to achieve half Imax after one population doubling (Imax/2). The C50 value for BrdUrd is 1.8±0.11 uM in the U-251 cell line.

Name

Type

Language

BROXURIDINE

Official Name

English

5-BROMO-1-((2R,4S,5R)-4-HYDROXY-5-(HYDROXYMETHYL)TETRAHYDROFURAN-2-YL)PYRIMIDINE-2,4(1H,3H)-DIONE

Systematic Name

English

URIDINE, 5-BROMO-2'-DEOXY-

Systematic Name

English

Broxuridine [WHO-DD]

Common Name

English

broxuridine [INN]

Common Name

English

NSC-38297

Code

English

BROMODEOXYURIDINE

Systematic Name

English

BROXURIDINE [JAN]

Common Name

English

BROXURIDINE [MART.]

Common Name

English

BROXURIDINE [MI]

Common Name

English

5-BROMO-2'-DEOXYURIDINE

Systematic Name

English

BUDR

Common Name

English

BROXURIDINE [HSDB]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

91295