The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

ICRF 186     4-[(2R)-1-(3,5- dioxopiperazin-1-yl)propan...

Synonyms: NCIMech_000085, NCIMech_000121, SureCN3339694, CCG-35198, CCG-35213, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ICRF 186

  • Studies in animals suggest that the bispiperazinedione ICRF-187 can prevent the development of dose-related doxorubicin-induced cardiac toxicity [1].
  • Antitumor response rates were similar (FDC vs. FDC + ICRF-187, 3 vs. 4 complete responses; 17 vs. 17 partial responses; and 9.3 vs. 10.3 months to disease progression) [1].
  • Although myelosuppression was slightly greater in the FDC + ICRF-187 group, the incidence of fever, infections, alopecia, nausea and vomiting, or death due to toxicity did not differ between the groups [1].
  • Control dogs received 0.9% NaCl solution i.v. 30 min after ICRF-187 i.p. (12.5 mg/kg body weight) [2].
  • Role of (+-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) in modulating free radical scavenging enzymes in doxorubicin-induced cardiomyopathy [3].

High impact information on ICRF 186

  • We conclude that ICRF-187 offers significant protection against cardiac toxicity caused by doxorubicin, without affecting the antitumor effect of doxorubicin or the incidence of noncardiac toxic reactions [1].
  • Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187 [4].
  • Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity [5].
  • Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change in expression of the beta isoform [5].
  • Western blots of topoisomerase IIalpha after incubation of CHO cells with ICRF-187 demonstrated a marked band depletion, whereas this effect was completely lacking in CHO/159-1 cells, and an equal effect of VP-16 was observed in both lines [6].

Chemical compound and disease context of ICRF 186


Biological context of ICRF 186


Anatomical context of ICRF 186


Associations of ICRF 186 with other chemical compounds


Gene context of ICRF 186

  • However, the killing caused by ICRF-193 and ICRF-187 is not enhanced by mutations in the RAD52 pathway [20].
  • However, BMY 25067-induced OH formation was more sensitive to inhibition by superoxide dismutase (SOD) and the iron chelator ICRF-187 [21].
  • Both the arrhythmia and the free radical signal were partially blocked by SOD, catalase and ICRF-187, indicating that iron-dependent oxygen radical formation from BMY-25282 (and possibly other compounds) is involved, in part, in inducing toxic manifestations in the rat heart and possibly in clinic [21].
  • Chronic treatment with these drugs or each combined with ICRF-187 did not change the antioxidant levels relative to the control values [17].
  • Selection of human leukemic CEM cells for resistance to the DNA topoisomerase II catalytic inhibitor ICRF-187 results in increased levels of topoisomerase IIalpha and altered G(2)/M checkpoint and apoptotic responses [22].

Analytical, diagnostic and therapeutic context of ICRF 186

  • Response rates to chemotherapy, event-free and overall survival, and noncardiac toxicities appear to be unaffected by the use of ICRF-187 [23].
  • Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines [5].
  • Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer [23].
  • Furthermore, normal morphology of the electron micrographs after treatment with doxorubicin and ICRF-187 indicated that ICRF-187 was cardioprotective [3].
  • The catalytic topoisomerase II inhibitor ICRF-187 prevented the effect when added to the cell culture before the UVA pulse but promoted it when added thereafter [14].


  1. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. Speyer, J.L., Green, M.D., Kramer, E., Rey, M., Sanger, J., Ward, C., Dubin, N., Ferrans, V., Stecy, P., Zeleniuch-Jacquotte, A. N. Engl. J. Med. (1988) [Pubmed]
  2. Reduction of chronic doxorubicin cardiotoxicity in dogs by pretreatment with (+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187). Herman, E.H., Ferrans, V.J. Cancer Res. (1981) [Pubmed]
  3. Role of (+-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) in modulating free radical scavenging enzymes in doxorubicin-induced cardiomyopathy. Alderton, P., Gross, J., Green, M.D. Cancer Res. (1990) [Pubmed]
  4. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Classen, S., Olland, S., Berger, J.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform. Wessel, I., Jensen, L.H., Jensen, P.B., Falck, J., Rose, A., Roerth, M., Nitiss, J.L., Sehested, M. Cancer Res. (1999) [Pubmed]
  6. Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor ICRF-159: a Tyr49Phe mutation confers high-level resistance to bisdioxopiperazines. Sehested, M., Wessel, I., Jensen, L.H., Holm, B., Oliveri, R.S., Kenwrick, S., Creighton, A.M., Nitiss, J.L., Jensen, P.B. Cancer Res. (1998) [Pubmed]
  7. Characterization of experimental mitoxantrone cardiotoxicity and its partial inhibition by ICRF-187 in cultured neonatal rat heart cells. Shipp, N.G., Dorr, R.T., Alberts, D.S., Dawson, B.V., Hendrix, M. Cancer Res. (1993) [Pubmed]
  8. Evidence of the selective alteration of anthracycline activity due to modulation by ICRF-187 (ADR-529). Green, M.D., Alderton, P., Gross, J., Muggia, F.M., Speyer, J.L. Pharmacol. Ther. (1990) [Pubmed]
  9. Mapping of DNA topoisomerase II poisons (etoposide, clerocidin) and catalytic inhibitors (aclarubicin, ICRF-187) to four distinct steps in the topoisomerase II catalytic cycle. Sehested, M., Jensen, P.B. Biochem. Pharmacol. (1996) [Pubmed]
  10. Effects of ICRF-187 on the cardiac and renal toxicity of epirubicin in spontaneously hypertensive rats. Dardir, M., Herman, E.H., Ferrans, V.J. Cancer Chemother. Pharmacol. (1989) [Pubmed]
  11. Morphologic and morphometric evaluation of the effect of ICRF-187 on bleomycin-induced pulmonary toxicity. Herman, E.H., Hasinoff, B.B., Zhang, J., Raley, L.G., Zhang, T.M., Fukuda, Y., Ferrans, V.J. Toxicology (1995) [Pubmed]
  12. Cell cycle progression and chromosome segregation in mammalian cells cultured in the presence of the topoisomerase II inhibitors ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane; ADR-529] and ICRF-159 (Razoxane). Gorbsky, G.J. Cancer Res. (1994) [Pubmed]
  13. dl-N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diaminopropane (ICRF-198) and d-1,2-bis(3,5-dioxopiperazine-1-yl)propane (ICRF-187) inhibition of Fe3+ reduction, lipid peroxidation, and CaATPase inactivation in heart microsomes exposed to adriamycin. Vile, G.F., Winterbourn, C.C. Cancer Res. (1990) [Pubmed]
  14. Enhanced processing of UVA-irradiated DNA by human topoisomerase II in living cells. Mielke, C., Christensen, M.O., Barthelmes, H.U., Boege, F. J. Biol. Chem. (2004) [Pubmed]
  15. Synergistic activity of doxorubicin and the bisdioxopiperazine (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187) against the murine sarcoma S180 cell line. Wadler, S., Green, M.D., Muggia, F.M. Cancer Res. (1986) [Pubmed]
  16. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. Speyer, J.L., Green, M.D., Zeleniuch-Jacquotte, A., Wernz, J.C., Rey, M., Sanger, J., Kramer, E., Ferrans, V., Hochster, H., Meyers, M. J. Clin. Oncol. (1992) [Pubmed]
  17. Comparative study of doxorubicin, mitoxantrone, and epirubicin in combination with ICRF-187 (ADR-529) in a chronic cardiotoxicity animal model. Alderton, P.M., Gross, J., Green, M.D. Cancer Res. (1992) [Pubmed]
  18. DNA damage signals induction of fas ligand in tumor cells. Mo, Y.Y., Beck, W.T. Mol. Pharmacol. (1999) [Pubmed]
  19. DNA topoisomerase II rescue by catalytic inhibitors: a new strategy to improve the antitumor selectivity of etoposide. Jensen, P.B., Sehested, M. Biochem. Pharmacol. (1997) [Pubmed]
  20. A novel mechanism of cell killing by anti-topoisomerase II bisdioxopiperazines. Jensen, L.H., Nitiss, K.C., Rose, A., Dong, J., Zhou, J., Hu, T., Osheroff, N., Jensen, P.B., Sehested, M., Nitiss, J.L. J. Biol. Chem. (2000) [Pubmed]
  21. Free-radical formation by mitomycin C and its novel analogs in cardiac microsomes and the perfused rat heart. Politi, P.M., Rajagopalan, S., Sinha, B.K. Biochim. Biophys. Acta (1989) [Pubmed]
  22. Selection of human leukemic CEM cells for resistance to the DNA topoisomerase II catalytic inhibitor ICRF-187 results in increased levels of topoisomerase IIalpha and altered G(2)/M checkpoint and apoptotic responses. Morgan, S.E., Cadena, R.S., Raimondi, S.C., Beck, W.T. Mol. Pharmacol. (2000) [Pubmed]
  23. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. Wexler, L.H., Andrich, M.P., Venzon, D., Berg, S.L., Weaver-McClure, L., Chen, C.C., Dilsizian, V., Avila, N., Jarosinski, P., Balis, F.M., Poplack, D.G., Horowitz, M.E. J. Clin. Oncol. (1996) [Pubmed]
WikiGenes - Universities