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
Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine.	1977 Jul	195058
Experimental teratological studies with the mouse CNS mutations cranioschisis and delayed splotch.	1985	3902948
Synthesis and antitumor and antiviral properties of 5-halo- and 5-(trifluoromethyl)-2'-deoxyuridine 3',5'-cyclic monophosphates and neutral triesters.	1986 Jul	3027328
Interaction of monoclonal antibodies directed against bromodeoxyuridine with pyrimidine bases, nucleosides, and DNA.	1986 Mar 1	3950402
Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides.	1989 Feb	2521518
Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemical responses detected in a sensitive new assay procedure.	1993 Jul	8243401
The regulation of alpha 5 beta 1 integrin expression in human muscle cells.	1994 Aug	7519154
Nature of the spermatogenic arrest in Dazl -/- mice.	2001 Sep	11514340
Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis.	2003	12881014
Recovery time of corneal epithelial proliferation in the rabbit following rigid gas-permeable extended contact-lens wear.	2003 Apr	12695703
Mitogenic effects of Brazilian arthropod venom on isolated islet beta cells: in vitro morphologic ultrastructural and functional studies.	2003 Mar	12643512
Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor.	2003 Oct	14563798
Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.	2003 Sep 15	12941330
Immunocytochemical identification of neoplastic cell clone in phase S of cell cycle in transplantable rat tumors.	2004	15478860
9HODE stimulates cell proliferation and extracellular matrix synthesis in human mesangial cells via PPARgamma.	2004 Nov	15522842
Influence of season and environment on adult neurogenesis in the central olfactory pathway of the shore crab, Carcinus maenas.	2004 Oct 29	15464748
Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth germs in a three-dimensional scaffold.	2006 Aug	16911102
The role of leptin in the development of the cerebral cortex in mouse embryos.	2006 Feb	16282354
3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.	2006 Feb 15	16290929
Effect of different wound dressings on cell viability and proliferation.	2006 Jun	16799377
Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells.	2006 Oct	16763198
Loss of input from the mossy cells blocks maturation of newly generated granule cells.	2007	17455193
Checkpoint independence of most DNA replication origins in fission yeast.	2007 Dec 19	18093330
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
5-Bromo-2-deoxyuridine activates DNA damage signalling responses and induces a senescence-like phenotype in p16-null lung cancer cells.	2007 Oct	17704656
Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation.	2008 Aug 19	18715114
Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain.	2009 Apr 10	19217927
[Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].	2009 Jan 20	19537031
Exhaustive in vivo labelling of plasmid DNA with BrdU for intracellular detection in non-viral transfection of mammalian cells.	2009 Oct	19670251
Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.	2010 Apr 16	20398374
Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8.	2010 Feb 22	20170548
FAK mediates the activation of cardiac fibroblasts induced by mechanical stress through regulation of the mTOR complex.	2010 Jun 1	20038548
A high-throughput screen for teratogens using human pluripotent stem cells.	2014 Jan	24154490

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