p53

Amifostine thiol can lessen the negative effects of both high and low LET radiation exposures, both immediately and later[1].
Amifostine thiolattenuates radiation-induced G1-phase arrest as well as DNA damage[1].
Amifostine thiol (4 mM; 30 minutes) defends RKO36 cells against chromosomal damage and degeneration brought on by ionizing radiation[1]
Amifostine thiol (4 mM; 30 minutes) prevents delayed genomic instability in irradiated RKO36 cells[1].
Amifostine thiol is toxic to RKO36 cells. At milimole levels, especially after prolonged treatment[1].
RKO36 cells are not protected by amifostine thiol at 40 μM from immediate chromosomal damage and cell death, but they are protected from delayed genomic instability.
Amifostine thiol activates JNK, which causes p53 to become phosphorylated at threonine 81[2].
In CHO AA8 cells, amifostine thiol alters the phosphorylation of topoisomerase IIα, changing the enzyme's activity and driving the cell cycle forward[3].

The findings demonstrated that amifostine thiol dihydrochloride (Amifostine thiol) reduced the severity of 6-OHDA-induced catalepsy (P<0.001), which was associated with 6-OHDA damage. Additionally, it was noted that when designed with varying dosages of amifostine thiol dihydrochloride (20, 40, and 80 μg/2 μL/pattern) prior to administering 6-OHDA, the dosing pattern was affected. After three days, it recovered to the typical range of OHDA damage state and dramatically (P<0.001) boosted SOD activity compared to 6-OHDA [4].

WR1065 is an aminothiol with selective cytoprotective effects in normal cells compared with cancer cells. In a previous study (North, S., El-Ghissassi, F., Pluquet, O., Verhaegh, G., and Hainaut, P. (2000) Oncogene 19, 1206-1214), we have shown that WR1065 activates wild-type p53 in cultured cells. Here we show that WR1065 induces p53 to accumulate through escape from proteasome-dependent degradation. This accumulation is not prevented by inhibitors of phosphatidylinositol 3-kinases and is not accompanied by phosphorylation of Ser-15, -20, or -37, which are common targets of the kinases activated in response to DNA damage. Furthermore, WR1065 activates the JNK (c-Jun N-terminal kinase), decreases complex formation between p53 and inactive JNK, and phosphorylates p53 at Thr-81, a known site of phosphorylation by JNK. A dominant negative form of JNK (JNK-APF) reduces by 50% the activation of p53 by WR1065. Thus, WR1065 activates p53 through a JNK-dependent signaling pathway. This pathway may prove useful for pharmacological modulation of p53 activity through non-genotoxic mechanisms.[2]

Compounds that can protect cells from the effects of radiation are important for clinical use, in the event of an accidental or terrorist-generated radiation event, and for astronauts traveling in space. One of the major concerns regarding the use of radio-protective agents is that they may protect cells initially, but predispose surviving cells to increased genomic instability later. In this study we used WR-1065, the active metabolite of amifostine, to determine how protection from direct effects of high- and low-LET radiation exposure influences genomic stability. When added 30 min before irradiation and in high concentrations, WR-1065 protected cells from immediate radiation-induced effects as well as from delayed genomic instability. Lower, nontoxic concentrations of WR-1065 did not protect cells from death; however, it was effective in significantly decreasing delayed genomic instability in the progeny of irradiated cells. The observed increase in manganese superoxide dismutase protein levels and activity may provide an explanation for this effect. These results confirm that WR-1065 is protective against both low- and high-LET radiation-induced genomic instability in surviving cells.[1]

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The effects of WR-1065 (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) II alpha activity, and topo II alpha phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. Exposure of CHO cells to 0.4 microM of WR-1065 for 30 min did not effect cell cycle progression nor topo II alpha activity and phosphorylation status. However, concentrations ranging from 4 microM to 4 mM were equally effective in significantly altering these three end points. Cell cycle progression was analysed by flow cytometry. Following a 30 min exposure to this range of concentrations, cells redistributed throughout the cell cycle with the most prominent changes being an accumulation of cells in G2. Topo II alpha activity was measured using a kinetoplast DNA (kDNA) decatenation assay. Enzyme activity was reduced by 50% relative to control levels throughout the 4 microM to 4 mM dose range tested. Likewise, topo II alpha phosphorylation levels, analysed using an immunoprecipitation assay and an antibody specific to the 170 kDa band of topo II, decreased between 42% to 48% of control levels. Inhibition of topo II alpha activity in cells exposed to WR-1065 is consistent with the associated observation of WR-1065 mediated cell cycle progression delay and build-up of cells in the G2 phase of the cell cycle.[3]

Seventy two male Wistar rats were divided into 9 equal groups and 6-OHDA (8 μg/2 μl/rat) was infused unilaterally into substantia nigra pars copmacta (SNc) to induce PD. Catalepsy was measured by standard bar test, CSF level of IL-6 was assessed by enzyme-linked immunosorbent assay (ELISA) method and SOD activity measured by spectrophotometric method. In pre-treatment groups WR-1065 (20, 40 and 80 μg/2 μl/rat/day, for 3 days) was infused into the SNc before 6-OHDA administration and 21 days later, as a recovery period, behavioral and molecular assay tests were done.[4]

mouse LD50 intraperitoneal 200 mg/kg

[1]. WR-1065, the Active Metabolite of Amifostine, Mitigates Radiation-Induced Delayed Genomic Instability. Free Radic Biol Med. 2008 Dec 15; 45(12): 1674-1681.

[2]. 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. J Biol Chem. 2003 Apr 4;278(14):11879-87.

[3]. WR-1065, an active metabolite of the cytoprotector amifostine, affects phosphorylation of topoisomerase IIα leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells. Cell Prolif. 1997 Jun; 30(6): 283-294.

[4]. 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

WR-1065 is an alkanethiol that is the N-3-aminopropyl derivative of cysteamine. Used as the S-phosphorylated prodrug, amifostine, for cytoprotection in cancer chemotherapy and radiotherapy. It has a role as a radiation protective agent, an antioxidant and a drug metabolite. It is a diamine and an alkanethiol. It is functionally related to a cysteamine.
2-((3-Aminopropyl)amino)ethanethiol has been reported in Apis cerana with data available.

C5H14N2S

134.24306

134.088

31098-42-7

Amifostine thiol dihydrochloride;14653-77-1

104807

White to off-white solid

Apis cerana

0.945

3

3

5

8

41.4

0

NCCCNCCS

YHPLKWQJMAYFCN-UHFFFAOYSA-N

InChI=1S/C5H14N2S/c6-2-1-3-7-4-5-8/h7-8H,1-6H2

2-(3-aminopropylamino)ethanethiol

Amifostine thiol; WR1065; 31098-42-7; Amifostine thiol; 2-((3-Aminopropyl)amino)ethanethiol; 2-(3-aminopropylamino)ethanethiol; WR 1065; WR-1065; Ethanethiol, 2-[(3-aminopropyl)amino]-; 2-[(3-aminopropyl)amino]ethanethiol; WR-1065

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~250 mg/mL (~1862.3 mM)
H2O: ~100 mg/mL (~744.93 mM; Need ultrasonic)

Solubility in Formulation 1: 16.67 mg/mL (124.18 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)