WR-1065

Modify Date: 2024-01-03 07:03:16

WR-1065 Structure
WR-1065 structure
Common Name WR-1065
CAS Number 14653-77-1 Molecular Weight 207.16
Density 0.975g/cm3 Boiling Point 218.6ºC at 760 mmHg
Molecular Formula C5H16Cl2N2S Melting Point N/A
MSDS Chinese USA Flash Point 86ºC
Symbol GHS05 GHS07
GHS05, GHS07
Signal Word Danger

 Use of WR-1065


WR-1065 dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling pathway.

 Names

Name Amifostine Thiol Dihydrochloride
Synonym More Synonyms

 WR-1065 Biological Activity

Description WR-1065 dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling pathway.
Related Catalog
Target

p53[1]

In Vitro The DNA-binding activity is increased in a WR-1065 dihydrochloride (WR-1065) concentration-dependent manner. Cells treated with 1 mM WR-1065 dihydrochloride for 24 h reveal that all of the p53-induced genes analyzed are transactivated following WR-1065 dihydrochloride treatment, in a p53-dependent manner. Significantly, treatment with WR-1065 dihydrochloride leads to a 3-fold increase in luciferase expression driven by AP-1, and a 5-fold increase when this reporter gene is driven by NF-κB, when these values are normalized to the level of the cotransfected β-galactosidase gene[2].
In Vivo The results show that wR-1065 dihydrochloride (WR-1065) attenuates the severity of 6-OHDA-induced catalepsy (P<0.001) when compare with 6-OHDA-lesioned rats. Also it has been observed that WR-1065 dihydrochloride improves catalepsy in dose dependent manner (P<0.001). Pretreatment with three different doses of WR-1065 dihydrochloride (20, 40 and 80 μg/2 μL/rat) for 3 days before 6-OHDA administration, significantly (P<0.001) elevates SOD activity and restores it to normal range compare with 6-OHDA lesioned rats[3].
Kinase Assay For Western analysis, cells are treated with 1 mM WR-1065 dihydrochloride (WR-1065) for 24 h, and subconfluent cultures of cells are harvested and lysed in RIPA buffer supplemented with protease inhibitors. Protein concentrations are determined by a detergent-compatible assay. Western blots are blocked and incubated in antibody in PBS/0.2% Tween 20/5% nonfat dry milk. Blots are incubated with 1 μg/mL antibody for 1 h at room temperature, followed by washing in PBS/0.2% Tween 20 and incubation in peroxidase-conjugated secondary antibody and chemiluminescence detection[2].
Cell Assay To test the effects of paclitaxel in the presence or absence of WR-1065 dihydrochloride (WR-1065) on cell growth, cells are seeded in 96-well tissue culture dishes at 20% confluence and allowed to attach and recover for at least 24 h. Varying combinations of paclitaxel alone or in combination with a 60 min pretreatment with 1 mM WR-1065 dihydrochloride are then added to each well, and the plates are incubated for an additional 48 h or 72 h. The number of surviving cells is determined by staining. The percentage of cells killed by paclitaxel and/or WR-1065 dihydrochloride is calculated as the percentage decrease in sulforhodamine B binding compare with control cells[2].
Animal Admin Seventy two rats are divided randomly into 9 equal groups: 1) Control group receives no injection and is left untreated for the entire period of the experiment as intact animals; 2) Sham operated group is subjected only to surgical procedure; 3) Vehicle (saline)-treated group receives 2 μL saline (intra-SNc); 4) Lesioned group receives 6-hydroxydopamine; 5) Vehicle+6OHDA group receives saline as a vehicle 3 days once daily (2 μL/rat) before 6-OHDA injection; 6 to 8) Rats in these groups are pretreated with intra-SNc injection of WR-1065 dihydrochloride (WR-1065) (20, 40 and 80 μg/2 μL/rat) 3 days before 6-OHDA injection; 9) Non-lesioned animals receive intra-SNc injection of WR-1065 dihydrochloride (80 μg/2 μL/rat) for three days[3].
References

[1]. Pluquet O, et al. The cytoprotective aminothiol WR1065 activates p53 through a non-genotoxic signaling pathway involving c-Jun N-terminal kinase. J Biol Chem. 2003 Apr 4;278(14):11879-87.

[2]. Shen H, et al. Binding of the aminothiol WR-1065 to transcription factors influences cellular response to anticancer drugs. J Pharmacol Exp Ther. 2001 Jun;297(3):1067-73.

[3]. Afshin Kheradmand, et al. Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats. Iran J Basic Med Sci. 2016 May; 19(5): 490-496.

 Chemical & Physical Properties

Density 0.975g/cm3
Boiling Point 218.6ºC at 760 mmHg
Molecular Formula C5H16Cl2N2S
Molecular Weight 207.16
Flash Point 86ºC
PSA 76.85000
LogP 1.74780
Vapour Pressure 0.124mmHg at 25°C
Index of Refraction 1.496
Storage condition 2-8℃

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
KJ0203000
CHEMICAL NAME :
Ethanethiol, 2-((3-aminopropyl)amino)-, dihydrochloride
CAS REGISTRY NUMBER :
14653-77-1
LAST UPDATED :
199707
DATA ITEMS CITED :
1
MOLECULAR FORMULA :
C5-H14-N2-S.2Cl-H
MOLECULAR WEIGHT :
207.19

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
400 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 24,48,1989

 Safety Information

Symbol GHS05 GHS07
GHS05, GHS07
Signal Word Danger
Hazard Statements H302-H318
Precautionary Statements P280-P305 + P351 + P338
RIDADR NONH for all modes of transport

 Articles26

More Articles
A manganese superoxide dismutase (SOD2)-mediated adaptive response.

Radiat. Res. 179(2) , 115-24, (2013)

Very low doses of ionizing radiation, 5 to 100 mGy, can induce adaptive responses characterized by elevation in cell survival and reduction in micronuclei formation. Utilizing these end points, RKO hu...

Aminothiol WR1065 induces differential gene expression in the presence of wild-type p53.

Oncogene 24(24) , 3964-75, (2005)

The aminothiol WR1065 exerts selective cytoprotective effects in normal cells compared to cancer cells and has clinical applications for the protection of normal cells in cancer patients undergoing ra...

Clinical pharmacokinetics of amifostine and WR1065 in pediatric patients with medulloblastoma.

Clin. Cancer Res. 16(3) , 1049-57, (2010)

We evaluated the pharmacokinetics of amifostine and WR1065 in pediatric patients with newly diagnosed medulloblastoma to assess the influence of patient covariates, including demographics, clinical ch...

 Synonyms

Ethanethiol, 2-[(3-aminopropyl)amino]-, hydrochloride (1:1)
2-(3-aminopropylamino)ethanethiol,dihydrochloride
2-[(3-Aminopropyl)amino]ethanethiol hydrochloride (1:1)
2-[(3-Aminopropyl)amino]ethanethiol dihydrochloride WR-1065 dihydrochloride
WR-1065 dihydrochloride
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