WR-1065

Names

[ Name ]:
WR-1065

[Synonym ]:
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

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]:

Signaling Pathways >> Apoptosis >> MDM-2/p53

Research Areas >> Cancer

[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.

[Related Small Molecules]

Pifithrin-α hydrobromide | RG7388 | Nutlin-3a | AMG232 | Pifithrin-β (hydrobromide) | Stylomycin aminonucleoside | RG7112 | APR-246 | NVP-HDM201 | SAR 405838 | RITA (NSC 652287) | NVP-CGM097 | Tenovin-1 | SJ 172550

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℃

MSDS

Click to get detail MSDS

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

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H318

[ Precautionary Statements ]:
P280-P305 + P351 + P338

[ RIDADR ]:
NONH for all modes of transport

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...