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 1447

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT00003832	Diagnostic	Phase II 1147	Unknown Approved Use Unknown
Acute myelogenous leukemia 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00003405	Primary	Phase II 1147	Unknown Approved Use Unknown
Hematologic malignancies 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00042250	Diagnostic	Phase II 1147	Unknown Approved Use Unknown
Brain cancer 10 Sources: https://adisinsight.springer.com/drugs/800009236	Primary	Phase III 665	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://adisinsight.springer.com/drugs/800009236	Diagnostic	Phase III 665	Unknown Approved Use Unknown
HIV-1 infection 156 Sources: https://clinicaltrials.gov/ct2/show/NCT00001650	Secondary	Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
35 mg/kg/day 1 times / day multiple, intraarterial MTD Dose: 35 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 35 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 2-3, 60%) Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/
25 mg/kg/day 1 times / day multiple, intraarterial Studied dose Dose: 25 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 25 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/	Other AEs: Thrombocytopenia, Nausea... Other AEs: Thrombocytopenia (grade 1, 84.6%) Nausea (grade 3, 7.7%) Hypertension (grade 3, 7.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/
25 mg/kg/day 1 times / day multiple, intraarterial Studied dose Dose: 25 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 25 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/	Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/

AEs

AE	Significance	Dose	Population
Thrombocytopenia	grade 2-3, 60% DLT	35 mg/kg/day 1 times / day multiple, intraarterial MTD Dose: 35 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 35 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8174116/
Thrombocytopenia	grade 1, 84.6%	25 mg/kg/day 1 times / day multiple, intraarterial Studied dose Dose: 25 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 25 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/
Hypertension	grade 3, 7.7%	25 mg/kg/day 1 times / day multiple, intraarterial Studied dose Dose: 25 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 25 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/
Nausea	grade 3, 7.7%	25 mg/kg/day 1 times / day multiple, intraarterial Studied dose Dose: 25 mg/kg/day, 1 times / day Route: intraarterial Route: multiple Dose: 25 mg/kg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7641176/

PubMed

Title	Date	PubMed
Bromodeoxyuridine (BrdU) treatment to measure hepatocellular proliferation does not mask furan-induced gene expression changes in mouse liver.	2014-09-02	24910943
A high-throughput screen for teratogens using human pluripotent stem cells.	2014-01	24154490
Characterization of pyrimidine nucleoside phosphorylase of Mycoplasma hyorhinis: implications for the clinical efficacy of nucleoside analogues.	2012-07-01	22475552
Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice.	2010-11	20816824
In the absence of Sonic hedgehog, p53 induces apoptosis and inhibits retinal cell proliferation, cell-cycle exit and differentiation in zebrafish.	2010-10-21	21042410
Acyclic retinoid NIK-333 accelerates liver regeneration and lowers serum transaminase activities in 70% partially hepatectomized rats, in vivo.	2010-09-25	20619257
Temporal patterns of blood flow and nitric oxide synthase expression affect macrophage accumulation and proliferation during collateral growth.	2010-09-16	20843382
FAK mediates the activation of cardiac fibroblasts induced by mechanical stress through regulation of the mTOR complex.	2010-06-01	20038548
Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.	2010-04-16	20398374
VILIP-1 expression in vivo results in decreased mouse skin keratinocyte proliferation and tumor development.	2010-04-15	20419170
Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8.	2010-02-22	20170548
Decreased neural stem/progenitor cell proliferation in mice with chronic/nonremitting experimental autoimmune encephalomyelitis.	2010	19786810
Exhaustive in vivo labelling of plasmid DNA with BrdU for intracellular detection in non-viral transfection of mammalian cells.	2009-10	19670251
Agonistic behavior enhances adult neurogenesis in male Acheta domesticus crickets.	2009-07	19525431
Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain.	2009-04-10	19217927
HAC stability in murine cells is influenced by nuclear localization and chromatin organization.	2009-03-06	19267891
[Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].	2009-01-20	19537031
Decreased postnatal neurogenesis in the hippocampus combined with stress experience during adolescence is accompanied by an enhanced incidence of behavioral pathologies in adult mice.	2008-12-17	19091092
High levels of anandamide, an endogenous cannabinoid, block the growth of sheep preimplantation embryos by inducing apoptosis and reversible arrest of cell proliferation.	2008-10	18614613
Apoptotic cell death, long-term persistence, and neuronal differentiation of aneuploid cells generated in the adult brain of teleost fish.	2008-09-01	18563701
Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation.	2008-08-19	18715114
Effects of gestational diethylstilbestrol treatment on male and female gonads during early embryonic development.	2008-08	18436715
[Effects of Xiehuo Bushen Decoction on survival and differentiation of transplanted neural stem cells in brains of rats with intracerebral hemorrhage].	2008-06	18559243
Activin in the brain modulates anxiety-related behavior and adult neurogenesis.	2008-04-02	18382659
Checkpoint independence of most DNA replication origins in fission yeast.	2007-12-19	18093330
The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts.	2007-11-02	17980035
NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice.	2007-06	17401437
Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle.	2007-05-11	17413043
Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats.	2007-04	17342331
Benzo[a]pyrene up-regulates the expression of the proliferating cell nuclear antigen (PCNA) and multixenobiotic resistance polyglycoprotein (P-gp) in Baltic Sea blue mussels (Mytilus edulis L.).	2007-03	17306628
Manipulation of cell cycle progression can counteract the apparent loss of correction frequency following oligonucleotide-directed gene repair.	2007-02-06	17284323
Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model.	2007-02	17191085
Downregulation of hnRNP C1/C2 by siRNA sensitizes HeLa cells to various stresses.	2007-02	16960656
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
Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth germs in a three-dimensional scaffold.	2006-08	16911102
Estrogen receptor-alpha and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands.	2006	16882347
The regulation of alpha 5 beta 1 integrin expression in human muscle cells.	1994-08	7519154
Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemical responses detected in a sensitive new assay procedure.	1993-07	8243401
Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro.	1990-07	2201250
Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides.	1989-02	2521518
Synthesis and antitumor and antiviral properties of 5-halo- and 5-(trifluoromethyl)-2'-deoxyuridine 3',5'-cyclic monophosphates and neutral triesters.	1986-07	3027328
Interaction of monoclonal antibodies directed against bromodeoxyuridine with pyrimidine bases, nucleosides, and DNA.	1986-03-01	3950402
The effects of 5-bromodeoxyuridine on fusion of the cranial neural folds in the mouse embryo.	1985-10	4049281
Experimental teratological studies with the mouse CNS mutations cranioschisis and delayed splotch.	1985	3902948
Strains of varicella-zoster virus resistant to 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil.	1984-06	6331298
Inhibition of polyoma virus-specific RNA formation by 5-bromo-2'-deoxyuridine.	1980	6262671
Antiviral and antineoplastic activities of pyrimidine arabinosyl nucleosides and their 5'-amino derivatives.	1979-10	229223
Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine.	1977-07	195058
Nucleosides. 3. Studies on 5-methylamino-2'-deoxyuridine as a specific antiherpes agent.	1966-05	5960908

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

NSC-38297

Preferred Name

English

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

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