mercaptoethylamines

Summary

Summary: Ethylamines, including CYSTEAMINE, that contain a sulfhydryl group in their structure.

Top Publications

  1. Grdina D, Murley J, Kataoka Y, Epperly W. Relationships between cytoprotection and mutation prevention by WR-1065. Mil Med. 2002;167:51-3 pubmed
    ..The ability to affect these postexposure processes makes WR-2721 an important agent in the reduction of the carcinogenic risks of environmental exposure to radiation or deleterious chemicals...
  2. QUINONES H, List A, Gerner E. Selective exclusion by the polyamine transporter as a mechanism for differential radioprotection of amifostine derivatives. Clin Cancer Res. 2002;8:1295-300 pubmed
    ..Selective exclusion of amifostine derivatives by the polyamine transporter could account for differential radio- or chemoprotection in normal versus neoplastic tissues in specific situations...
  3. Pluquet O, North S, Bhoumik A, Dimas K, RONAI Z, Hainaut P. The cytoprotective aminothiol WR1065 activates p53 through a non-genotoxic signaling pathway involving c-Jun N-terminal kinase. J Biol Chem. 2003;278:11879-87 pubmed
    ..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...
  4. Grdina D, Sigdestad C, Dale P, Perrin J. The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair. Br J Cancer. 1989;59:17-21 pubmed
    ..These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by gamma-rays...
  5. Michelutti A, Stocchi R, Candoni A, Tiribelli M, Calistri E, Russo D, et al. Effect of amifostine on the cytotoxicity of daunorubicin and daunoxome in tumor and normal cells. Cancer Chemother Pharmacol. 2006;57:517-24 pubmed
    ..These patients may be candidates for alternative therapeutic strategies and the combination of DNX and Amifostine is an attractive treatment for these cases where a low nonhematological toxicity is required...
  6. Cassatt D, Fazenbaker C, Kifle G, Bachy C. Effects of dose and schedule on the efficacy of ethyol: preclinical studies. Semin Oncol. 2003;30:31-9 pubmed
  7. Evans H, Evans T, Horng M. Antimutagenicity of WR-1065 in L5178Y cells exposed to accelerated (56)Fe ions. Radiat Res. 2002;158:110-4 pubmed
    ..The results indicate that the mechanisms involved differ in the protection against cytotoxic compared to mutagenic effects and in the protection against damage caused by accelerated (56)Fe ions compared to X radiation...
  8. Zheng S, Newton G, Gonick G, Fahey R, Ward J. Radioprotection of DNA by thiols: relationship between the net charge on a thiol and its ability to protect DNA. Radiat Res. 1988;114:11-27 pubmed
    ..1 to 0.7 mol dm-3 MgSO4. Since this change causes poly(dG,dC), but not calf thymus DNA, to undergo a change from the B-form to the Z-form of DNA, both forms must have a comparable susceptibility to radiation-induced base release...
  9. Grdina D, Murley J, Miller R, Mauceri H, Sutton H, Thirman M, et al. A manganese superoxide dismutase (SOD2)-mediated adaptive response. Radiat Res. 2013;179:115-24 pubmed publisher
    ..While very low radiation doses require an intact TNF signaling process to induce a SOD2-mediated adaptive response, amifostine can induce a similar adaptive response in both TNF receptor competent and knockout cells, respectively...

More Information

Publications62

  1. Grdina D, Nagy B, Hill C, Sigdestad C. Protection against radiation-induced mutagenesis in V79 cells by 2-[(aminopropyl)amino] ethanethiol under conditions of acute hypoxia. Radiat Res. 1989;117:251-8 pubmed
  2. Yang H, Erdos E, Chiang T. New enzymatic route for the inactivation of angiotensin. Nature. 1968;218:1224-6 pubmed
  3. Koukourakis M. Amifostine: is there evidence of tumor protection?. Semin Oncol. 2003;30:18-30 pubmed
  4. Snyder R, Grdina D. Further evidence that the radioprotective aminothiol, WR-1065, catalytically inactivates mammalian topoisomerase II. Cancer Res. 2000;60:1186-8 pubmed
    ..These studies also suggest that WR-1065 might be expected to reduce the toxicity and clastogenicity in clinical applications of etoposide or quinolone antibiotics in dose-limiting normal tissues...
  5. Kim I, Oh T. 2-Mercaptoethylamine, radioprotector, inhibits the induction of the oxidative stress-inducible (soi) gene by paraquat in Escherichia coli. Pharmacol Res. 2000;42:429-33 pubmed
    ..At concentrations above 1 mm, MEA effectively inhibited the NBT reduction in a concentration-dependent fashion. Our results demonstrated that MEA has an ability to scavenge.O(2)(-), and so protects against.O(2)(-)-mediated damage...
  6. Schor N. Mechanisms of synergistic toxicity of the radioprotective agent, WR2721, and 6-hydroxydopamine. Biochem Pharmacol. 1988;37:1751-62 pubmed
    ..Oxygen radicals not only inactivated the synthetase, as well, but hastened the oxidation of the free thiol metabolite of WR2721 to its corresponding disulfide...
  7. Rappeneau S, Baeza Squiban A, Marano F, Calvet J. Efficient protection of human bronchial epithelial cells against sulfur and nitrogen mustard cytotoxicity using drug combinations. Toxicol Sci. 2000;58:153-60 pubmed
    ..One of these combinations, NAC + DOX, appeared to be the most interesting, as these agents are already used in human therapy. It exhibited good efficacy in delayed cotreatment (up to 90 min) against SM...
  8. Fulda S, Fichtner I, Hero B, Berthold F. Preclinical and clinical aspects on the use of amifostine as chemoprotector in neuroblastoma patients. Med Pediatr Oncol. 2001;36:199-202 pubmed
    ..In several studies in adults, amifostine (WR-2721) and its active metabolite WR-1065 have shown protection against myelo- and nephrotoxicity of chemotherapeutic agents without compromising cytotoxic efficacy to the tumor...
  9. Yu Z, Eaton J, Persson H. The radioprotective agent, amifostine, suppresses the reactivity of intralysosomal iron. Redox Rep. 2003;8:347-55 pubmed
    ..These findings suggest a single and plausible explanation for the radioprotective effects of amifostine and may provide a basis for the design of even more effective radio- and chemoprotective drugs...
  10. Hoffmann G, Buccola J, Merz M, Littlefield L. Structure-activity analysis of the potentiation by aminothiols of the chromosome-damaging effect of bleomycin in G0 human lymphocytes. Environ Mol Mutagen. 2001;37:117-27 pubmed
    ..These studies suggest that potentiation of the clastogenic action of BLM by aminothiols can be explained by the combination of a thiol-mediated redox mechanism and an amine-mediated targeting of the thiol function to DNA...
  11. Murley J, Kataoka Y, Cao D, Li J, Oberley L, Grdina D. Delayed radioprotection by NFkappaB-mediated induction of Sod2 (MnSOD) in SA-NH tumor cells after exposure to clinically used thiol-containing drugs. Radiat Res. 2004;162:536-46 pubmed
  12. Vaughan A, Grdina D, Meechan P, Milner A, Gordon D. Conformational changes in chromatin structure induced by the radioprotective aminothiol, WR 1065. Br J Cancer. 1989;60:893-6 pubmed
    ..It is proposed that perturbation of replicon supercoiling affects the process of normal DNA synthesis and strand break rejoining, allowing a longer time for the accurate repair of DNA damage...
  13. Banerjee S, Maresca K, Stephenson K, Valliant J, Babich J, Graham W, et al. N,N-bis(2-mercaptoethyl)methylamine: a new coligand for Tc-99m labeling of hydrazinonicotinamide peptides. Bioconjug Chem. 2005;16:885-902 pubmed
  14. Li C, Wang S, Huang T, Chen N, Ou M. Feasibility study of the pharmacology of local application of amifostine (WR-2721) to the buccal mucosa in guinea pigs. Pharmacology. 2013;91:281-6 pubmed publisher
    ..We have undertaken this study to investigate the feasibility of topical application of the radioprotective compound WR-2721 to the buccal mucosa...
  15. Schwartz J, Giovanazzi S, Karrison T, Jones C, Grdina D. 2-[(Aminopropyl)amino] ethanethiol-mediated reductions in 60Co gamma-ray and fission-spectrum neutron-induced chromosome damage in V79 cells. Radiat Res. 1988;113:145-54 pubmed
    ..Thus the radioprotector WR1065 is an effective anti-clastogenic agent in V79 cells, protecting against both 60Co gamma-ray and fission-spectrum neutron-induced aberrations, when present during irradiation...
  16. Proskuriakov S, Kucherenko N, Semenenko M, Trishkina A, Trofimova T, Shtein L, et al. [NO-inhibiting activity of radioprotectors]. Radiats Biol Radioecol. 2003;43:51-5 pubmed
    ..The analysis of the relevant literature has confirmed the phenomenon described by the authors: radioprotectors show NO-inhibiting activity...
  17. Pendergrass J, Srinivasan V, Kumar K, Jackson W, Seed T. Determination of WR-1065 and WR-33278 by liquid chromatography with electrochemical detection. J AOAC Int. 2002;85:551-4 pubmed
    ..Within- and between-day determinations of measurement Vision and accuracy for both compounds validated the suitability of this assay method...
  18. Symon Z, Levi M, Ensminger W, Smith D, Lawrence T. Selective radioprotection of hepatocytes by systemic and portal vein infusions of amifostine in a rat liver tumor model. Int J Radiat Oncol Biol Phys. 2001;50:473-8 pubmed
  19. Smoluk G, Fahey R, Ward J. Interaction of glutathione and other low-molecular-weight thiols with DNA: evidence for counterion condensation and coion depletion near DNA. Radiat Res. 1988;114:3-10 pubmed
    ..They provide a rationale for enhanced effectiveness of WR 1065 and cysteamine as radioprotectors compared to neutral and anionic thiols and suggest that anionic thiols such as GSH should be poor radioprotectors of DNA...
  20. Harman D. Free radical theory of aging: dietary implications. Am J Clin Nutr. 1972;25:839-43 pubmed
  21. Fouladi M, Stempak D, Gammon J, Klein J, Grant R, Greenberg M, et al. Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma. Cancer. 2001;92:914-23 pubmed
  22. Belkacemi Y, Rat P, Piel G, Christen M, Touboul E, Warnet J. Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation. Int J Cancer. 2001;96 Suppl:15-26 pubmed
    ..They are currently used in preventing radiation-induced xerostomia and should be further tested in the prevention of late radiation-induced ocular complications such as sicca syndrome and cataract...
  23. McKibbin T, Panetta J, Fouladi M, Gajjar A, Bai F, Okcu M, et al. Clinical pharmacokinetics of amifostine and WR1065 in pediatric patients with medulloblastoma. Clin Cancer Res. 2010;16:1049-57 pubmed publisher
  24. Grdina D, Murley J, Kataoka Y, Baker K, Kunnavakkam R, Coleman M, et al. Amifostine induces antioxidant enzymatic activities in normal tissues and a transplantable tumor that can affect radiation response. Int J Radiat Oncol Biol Phys. 2009;73:886-96 pubmed publisher
    ..To determine whether amifostine can induce elevated manganese superoxide dismutase (SOD2) in murine tissues and a transplantable SA-NH tumor, resulting in a delayed tumor cell radioprotective effect...
  25. Bai F, Kirstein M, Hanna S, Stewart C. New liquid chromatographic assay with electrochemical detection for the measurement of amifostine and WR1065. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;772:257-65 pubmed
    ..Furthermore, the application of a coulometric electrode is more efficient and requires less maintenance than previously published methods for the two compounds...
  26. Ben Josef E, Han S, Tobi M, Shaw L, Bonner H, Vargas B, et al. A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury. Int J Radiat Oncol Biol Phys. 2002;53:1160-4 pubmed
  27. Badawy Z, Souid A. Inhibition of human sperm respiration by 4-hydroperoxycyclophosphamide and protection by mesna and WR-1065. Fertil Steril. 2009;91:173-8 pubmed publisher
    ..To determine the effect of 4-hydroperoxycyclophosphamide (4OOH-CP) on the respiration of human sperm, and investigate the protective properties of mesna and WR-1065...
  28. Kataoka Y, Murley J, Khodarev N, Weichselbaum R, Grdina D. Activation of the nuclear transcription factor kappaB (NFkappaB) and differential gene expression in U87 glioma cells after exposure to the cytoprotector amifostine. Int J Radiat Oncol Biol Phys. 2002;53:180-9 pubmed
    ..Amifostine's active free thiol WR-1065 was investigated to determine its effect on nuclear transcription factor kappaB (NFkappaB) activation and subsequent gene expression in U87 glioma cells...
  29. Michieli M, Michelutti A, Damiani D, Ermacora A, Masolini P, Stocchi R, et al. Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines. Leuk Lymphoma. 2001;42:721-9 pubmed
    ..The observation that even the WR-1065 metabolite gave no protection against Anthracyclines toxicity strengthened the data and provided confirmation for the further in vivo testing of the safety and efficacy of Amifostine in leukemias...
  30. Pluquet O, North S, Richard M, Hainaut P. Activation of p53 by the cytoprotective aminothiol WR1065: DNA-damage-independent pathway and redox-dependent modulation of p53 DNA-binding activity. Biochem Pharmacol. 2003;65:1129-37 pubmed
    ..Direct reduction by WR1065 of key cysteines in p53 may play an important role in this alternative pathway, as shown by the fact that WR1065 activated the redox-dependent, DNA-binding activity of p53 in vitro...
  31. Wilmore B, Cassidy P, Warters R, Roberts J. Thiazolidine prodrugs as protective agents against gamma-radiation-induced toxicity and mutagenesis in V79 cells. J Med Chem. 2001;44:2661-6 pubmed
    ..The 2-oxothiazolidine analogues showed little activity in either determination under the conditions tested, perhaps due to their enhanced chemical and biochemical stability...
  32. Bykov V, Selivanova G, Wiman K. Small molecules that reactivate mutant p53. Eur J Cancer. 2003;39:1828-34 pubmed
    ..Various types of small molecules have been identified that can restore native conformation and wild-type function to mutant p53. Such molecules may serve as leads for the development of novel efficient anticancer drugs...
  33. Horvath G, Takats A. Effect of radioprotectors on the aggregability, cAMP and thiol content of blood platelets. Acta Physiol Hung. 1995;83:389-402 pubmed
    ..The slight elevation of AC-activity caused by low doses of WR-1065 also suggest that the AC-complex consists of unevenly sensitive subunits (G-proteins, catalytic subunit)...
  34. Dziegielewski J, Goetz W, Murley J, Grdina D, Morgan W, Baulch J. Amifostine metabolite WR-1065 disrupts homologous recombination in mammalian cells. Radiat Res. 2010;173:175-83 pubmed publisher
    ..This suppression of hyper-recombination is a previously unrecognized mechanism by which WR-1065 effects radioprotection in mammalian cells...
  35. Mann K. Methods for the study of redox-mediated changes in p53 structure and function. Methods Mol Biol. 2008;476:117-38 pubmed
  36. Pamujula S, Kishore V, Rider B, Agrawal K, Mandal T. Radioprotection in mice following oral administration of WR-1065/PLGA nanoparticles. Int J Radiat Biol. 2008;84:900-8 pubmed publisher
    ..This report describes for the first time an oral formulation of WR-1065 and follows on from our earlier report of a similar oral formulation of amifostine...
  37. Tacchini L, Dansi P, Matteucci E, Bernelli Zazzera A, Desiderio M. Influence of proteasome and redox state on heat shock-induced activation of stress kinases, AP-1 and HSF. Biochim Biophys Acta. 2001;1538:76-89 pubmed
    ..AP-1 and HSF show opposite patterns of response to HS in the presence of proteasome inhibitors or reducing agents...
  38. Walker D, Kajon A, Torres S, Carter M, McCash C, Swenberg J, et al. WR1065 mitigates AZT-ddI-induced mutagenesis and inhibits viral replication. Environ Mol Mutagen. 2009;50:460-72 pubmed publisher
    ..These findings suggest that the activities have a possible common mode of action that merits further investigation...
  39. Grdina D, Murley J, Kataoka Y, Calvin D. Differential activation of nuclear transcription factor kappaB, gene expression, and proteins by amifostine's free thiol in human microvascular endothelial and glioma cells. Semin Radiat Oncol. 2002;12:103-11 pubmed
    ..5 times above control levels over this same period. WR1065 had no effect on the levels of adhesion molecules, cytokines, and growth factors secreted by cells exposed for up to 24 hours as measured by enzyme-linked immunosorbent assay...
  40. Murley J, Kataoka Y, Miller R, Li J, Woloschak G, Grdina D. SOD2-mediated effects induced by WR1065 and low-dose ionizing radiation on micronucleus formation in RKO human colon carcinoma cells. Radiat Res. 2011;175:57-65 pubmed publisher
    ..SOD2 played an important role in the adaptive/delayed radioprotective response by inhibiting the initiation of a superoxide anion-induced ROS cascade leading to enhanced mitochondrial and nuclear damages...
  41. Murley J, Kataoka Y, Hallahan D, Roberts J, Grdina D. Activation of NFkappaB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells. Free Radic Biol Med. 2001;30:1426-39 pubmed
    ..MnSOD expression rose by 2-fold and remained elevated from 4 to 22 h following SH exposure...
  42. Murley J, Kataoka Y, Weydert C, Oberley L, Grdina D. Delayed radioprotection by nuclear transcription factor kappaB -mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger WR1065. Free Radic Biol Med. 2006;40:1004-16 pubmed
  43. Amat E, Prieto M, Moreno V. Comparative study between the interaction of dephosphorylated amifostine (WR-1065) and amoxicilline with pBR322 in absence and presence of cisplatin by AFM. Int J Pharm. 2004;270:75-82 pubmed
    ..This effect can justify the role as protecting agent of amifostine on side effects caused by cisplatin and can open new possibilities to other agents like amoxicilline...
  44. Li P, Liu Y, Wang X, Tang B. A new FRET nanoprobe for trypsin using a bridged ?-cyclodextrin dimer-dye complex and its biological imaging applications. Analyst. 2011;136:4520-5 pubmed publisher
    ..The nanoprobe has good biological applicability and provides a potential assay for further clinical research of trypsin in biosystems...
  45. Murley J, Baker K, Miller R, Darga T, Weichselbaum R, Grdina D. SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF signaling and amifostine. Free Radic Biol Med. 2011;51:1918-25 pubmed publisher
    ..Under the conditions tested, TNFR1 and 2 inhibition negatively affected the low-dose radiation-induced but not the thiol-induced adaptive responses observed to be mediated by elevations in SOD2 activity...
  46. Murray D, vanAnkeren S, Milas L, Meyn R. Radioprotective action of WR-1065 on radiation-induced DNA strand breaks in cultured Chinese hamster ovary cells. Radiat Res. 1988;113:155-70 pubmed
    ..Based on these observations, it would appear that the molecular actions of aminothiol radioprotective compounds that lead to reduced cell killing are much more complex than previously thought...
  47. Samiei N, Mangas Sanjuan V, Gonzalez Alvarez I, Foroutan M, Shafaati A, Zarghi A, et al. Ion-pair strategy for enabling amifostine oral absorption: rat in situ and in vivo experiments. Eur J Pharm Sci. 2013;49:499-504 pubmed publisher
    ..In summary ion pair strategy with succinic acid could enable amifostine oral administration on enteric coated formulations. ..
  48. Cassatt D, Fazenbaker C, Kifle G, Bachy C. Subcutaneous administration of amifostine (ethyol) is equivalent to intravenous administration in a rat mucositis model. Int J Radiat Oncol Biol Phys. 2003;57:794-802 pubmed
    ..To determine whether SC administration was equivalent to IV administration, we used models to follow pharmacokinetics and oral mucosal protection in rats...
  49. Kumar K, Singh V, Jackson W, Seed T. Inhibition of LPS-induced nitric oxide production in RAW cells by radioprotective thiols. Exp Mol Pathol. 2003;74:68-73 pubmed
  50. Grdina D, Nagy B, Hill C, Wells R, Peraino C. The radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells. Carcinogenesis. 1985;6:929-31 pubmed
  51. Whiteside W, Sears D, Young P, Rubin D. Properties of selected S-nitrosothiols compared to nitrosylated WR-1065. Radiat Res. 2002;157:578-88 pubmed
    ..These observations indicate that, relative to other nitrosylated non-protein thiols, the S-nitrosothiol of WR-1065 is an unstable non-protein S-nitrosothiols with a high reactive potential in the modification of protein thiols...
  52. Tacka K, Dabrowiak J, Goodisman J, Souid A. Kinetic analysis of the reactions of 4-hydroperoxycyclophosphamide and acrolein with glutathione, mesna, and WR-1065. Drug Metab Dispos. 2002;30:875-82 pubmed
    ..When WR-1065 and mesna were used together, the protection against cellular depletion of GSH was additive. Our results are relevant to the administration of thiol drugs with high-dose alkylating agents...
  53. Merlin J, Marchal S, Ramacci C, Berlion M, Poullain M. Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines. Anticancer Drugs. 2002;13:141-7 pubmed
    ..The present results demonstrating that amifostine or its main active metabolite do not impair the cytotoxicity of fotemustine justify an extensive clinical evaluation of this combination in metastatic melanoma...