coformycin

Summary

Summary: A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.

Top Publications

  1. Merkler D, Brenowitz M, Schramm V. The rate constant describing slow-onset inhibition of yeast AMP deaminase by coformycin analogues is independent of inhibitor structure. Biochemistry. 1990;29:8358-64 pubmed
    R)- and (S)-2'-deoxycoformycin, (R)-coformycin, and the corresponding 5'-monophosphates were compared as inhibitors of yeast AMP deaminase. The overall inhibition constants ranged from 4...
  2. Han B, Bingman C, Mahnke D, Sabina R, Phillips G. Crystallization and preliminary X-ray crystallographic analysis of adenosine 5'-monophosphate deaminase (AMPD) from Arabidopsis thaliana in complex with coformycin 5'-phosphate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005;61:740-2 pubmed
    ..Crystals of purified AtAMPD have been obtained to which coformycin 5'-phosphate, a transition-state inhibitor, is bound...
  3. Tedde A, Balis M, Ikehara S, Pahwa R, Good R, Trotta P. Animal model for immune dysfunction associated with adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1980;77:4899-903 pubmed
    ..4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man. ..
  4. Marongiu M, Pani A, Tinti E, Grifantini M, Franchetti P, Cristalli G, et al. Enhancement of the anti-HIV-1 activity of ddAdo by coformycin, EHNA and deaza-EHNA derivatives. New Microbiol. 1995;18:359-70 pubmed
    ..of ddAdo, we studied its anti-HIV-1 activity in the presence of different adenosine deaminase inhibitors, namely Coformycin (CF), 9-(erythro-2-hydroxy-3-nonyl) adenine (EHNA) and some deaza-EHNA derivatives...
  5. Werner A, Siems W, Schmidt H, Rapoport I, Gerber G, Toguzov R, et al. Determination of nucleotides, nucleosides and nucleobases in cells of different complexity by reversed-phase and ion-pair high-performance liquid chromatography. J Chromatogr. 1987;421:257-65 pubmed
    ..During glucose-free incubation, human red cells accumulate adenosine and adenine in the presence of coformycin owing to the inhibition of adenosine and AMP deamination...
  6. Bennett L, Brockman R, Allan P, Rose L, Shaddix S. Alterations in nucleotide pools induced by 3-deazaadenosine and related compounds. Role of adenylate deaminase. Biochem Pharmacol. 1988;37:1233-44 pubmed
    ..This explanation is supported by two observations: (a) coformycin, an inhibitor of AMP deaminase, prevented the effects on nucleotide pools, and (b) 3-deazaadenine decreased the ..
  7. O Dwyer P, Wagner B, Leyland Jones B, Wittes R, Cheson B, Hoth D. 2'-Deoxycoformycin (pentostatin) for lymphoid malignancies. Rational development of an active new drug. Ann Intern Med. 1988;108:733-43 pubmed
    ..Pentostatin is valuable for treatment of indolent lymphoid malignancies and may be useful in non-cancer-related lymphocyte research. ..
  8. Franco R, Hoyle C, Centelles J, Burnstock G. Degradation of adenosine by extracellular adenosine deaminase in the rat duodenum. Gen Pharmacol. 1988;19:679-81 pubmed
    ..5. The extracellular adenosine deaminase activity (4 units/g tissue) was high compared with activity previously determined in other organs. ..
  9. Toledo F, Smith K, Buttin G, Debatisse M. The evolution of the amplified adenylate deaminase 2 domains in Chinese hamster cells suggests the sequential operation of different mechanisms of DNA amplification. Mutat Res. 1992;276:261-73 pubmed
    ..The nature of segregative amplification mechanisms operating in these processes and the possible involvement of replicative ones are discussed. ..

More Information

Publications62

  1. Klenow H, Ostergaard E. Adenosine induction of rapid catabolism of adenine ribonucleotides and independent elevation of the ATP content in quiescent mouse fibroblasts. J Cell Physiol. 1988;137:565-70 pubmed
    ..Experiments with varying concentrations of coformycin (an inhibitor of adenosine 5'-monophosphate [AMP] deaminase and adenosine deaminase) and of 5'-amino-5'-..
  2. Cummings F, Crabtree G, Wiemann M, Spremulli E, Parks R, Calabresi P. Clinical, pharmacologic, and immunologic effects of 2'-deoxycoformycin. Clin Pharmacol Ther. 1988;44:501-9 pubmed
  3. Begleiter A, Pugh L, Israels L, Johnston J. Enhanced cytotoxicity and inhibition of DNA damage repair in irradiated murine L5178Y lymphoblasts and human chronic lymphocytic leukemia cells treated with 2'-deoxycoformycin and deoxyadenosine in vitro. Cancer Res. 1988;48:3981-6 pubmed
    ..These results suggest that 2'-deoxycoformycin/deoxyadenosine can function as a radiosensitizer, and this effect is associated with the cellular accumulation of dATP and inhibition of repair of DNA single strand breaks...
  4. Brito Babapulle F, Huang D, Lavender P, Galton D, Catovsky D. Regression of intracerebral lesions in T prolymphocytic leukaemia treated with intravenous deoxycoformycin. Eur J Haematol. 1988;40:185-7 pubmed
    ..Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started. ..
  5. Monks N, Fraser L. Inhibition of adenosine-metabolizing enzymes modulates mouse sperm fertilizing ability: a changing role for endogenously generated adenosine during capacitation. Gamete Res. 1988;21:267-76 pubmed
    ..Conversely, inhibition of adenosine deaminase with 100 nM coformycin, to increase available endogenous adenosine, promoted the fertilizing ability of partially capacitated ..
  6. Thaler J, Denz H, Dietze O, Gastl G, Ho A, Gattringer C, et al. Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin. Leuk Res. 1989;13:377-83 pubmed
    ..This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission. ..
  7. Germann U, Gottesman M, Pastan I. Expression of a multidrug resistance-adenosine deaminase fusion gene. J Biol Chem. 1989;264:7418-24 pubmed
    ..The data indicate that the human multidrug resistance gene may be used as a dominant selectable marker to introduce other genes in the form of gene fusions into cultured cells. ..
  8. Takeda E, Kuroda Y, Naito E, Yokota I, Saijo T, Hirose M, et al. Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes. J Inherit Metab Dis. 1991;14:87-95 pubmed
  9. Dancer J, Hughes R, Lindell S. Adenosine-5'-phosphate deaminase. A novel herbicide target. Plant Physiol. 1997;114:119-29 pubmed
    The isolation of carbocyclic coformycin as the herbicidally active component from a fermentation of Saccharothrix species was described previously (B.D. Bush, G.V. Fitchett, D.A. Gates, D. Langley [1993] Phytochemistry 32: 737-739)...
  10. Decking U, Juengling E, Kammermeier H. Interstitial transudate concentration of adenosine and inosine in rat and guinea pig hearts. Am J Physiol. 1988;254:H1125-32 pubmed
    ..2 microM, with no change in coronary flow response to hypoxia. High concentrations of coformycin (Streptomyces antibioticus), an adenosine deaminase inhibitor (greater than 1 microM), were necessary to ..
  11. Niedzwicki J, Abernethy D. Structure-activity relationship of ligands of human plasma adenosine deaminase2. Biochem Pharmacol. 1991;41:1615-24 pubmed
    ..b>Coformycin and 2'-deoxycoformycin were by far the most potent inhibitors of this isoenzyme (apparent Ki values 20 and 19 nM,..
  12. Hosmane R, Hong M. How important is the N-3 sugar moiety in the tight-binding interaction of coformycin with adenosine deaminase?. Biochem Biophys Res Commun. 1997;236:88-93 pubmed
    Preliminary findings on the possible important role of the N-3 sugar moiety of coformycin in its tight-binding interaction with adenosine deaminase (ADA) are reported...
  13. Merkler D, Schramm V. Catalytic and regulatory site composition of yeast AMP deaminase by comparative binding and rate studies. Resolution of the cooperative mechanism. J Biol Chem. 1990;265:4420-6 pubmed
    ..At 0.7 M KCl, ATP binds to the enzyme, but no longer activates. Titration with coformycin 5'-monophosphate, a slow, tight-binding inhibitor, indicates a single catalytic site/subunit...
  14. Lindell S, Moloney B, Hewitt B, Earnshaw C, Dudfield P, Dancer J. The design and synthesis of inhibitors of adenosine 5'-monophosphate deaminase. Bioorg Med Chem Lett. 1999;9:1985-90 pubmed
    Carbocylic coformycin (4) is a potent herbicide whose primary mode of action involves inhibition of adenosine 5'-monophosphate deaminase (AMPDA) following phosphorylation of the 5'-hydroxyl group in vivo...
  15. Lupidi G, Falasca M, Marmocchi F, Venardi G, Cristalli G, Riva F. Adenosine deaminase from bovine brain: purification and partial characterization. Biochem Int. 1992;26:1053-63 pubmed
    ..Kinetic constants for the association and dissociation of coformycin and 2'-deoxycoformycin with the bovine brain adenosine deaminase are reported.
  16. Kuroki Y, Shimoyama M, Inaba S, Hirose M. Potentiation of growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine by 2'-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas. Jpn J Cancer Res. 1989;80:482-9 pubmed
    ..These results suggest that the combination of DCF and Ara-A may be effective against various types of lymphoid malignancies and some myeloid leukemias. ..
  17. Marrone T, Straatsma T, Briggs J, Wilson D, Quiocho F, McCammon J. Theoretical study of inhibition of adenosine deaminase by (8R)-coformycin and (8R)-deoxycoformycin. J Med Chem. 1996;39:277-84 pubmed
    ..dynamics and free energy simulations were performed to examine the binding of (8R)-deoxycoformycin and (8R)-coformycin to adenosine deaminase...
  18. Komarova S, Mosharov E, Vitvitsky V, Ataullakhanov F. Adenine nucleotide synthesis in human erythrocytes depends on the mode of supplementation of cell suspension with adenosine. Blood Cells Mol Dis. 1999;25:170-9 pubmed
    ..In the presence of coformycin, erythrocytes utilised adenosine at a rate of 0.2-0.3 mmol/l cells h...
  19. Stromski M, van Waarde A, Avison M, Thulin G, Gaudio K, Kashgarian M, et al. Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats. J Clin Invest. 1988;82:1694-9 pubmed
    ..Inhibition of adenosine deaminase during ischemia results in a injury similar to that seen after a shorter period of insult. ..
  20. Priebe T, Kandil O, Nakic M, Pan B, Nelson J. Selective modulation of antibody response and natural killer cell activity by purine nucleoside analogues. Cancer Res. 1988;48:4799-803 pubmed
  21. Sandhu G, Burrier A, Janero D. Adenosine deaminase inhibitors attenuate ischemic injury and preserve energy balance in isolated guinea pig heart. Am J Physiol. 1993;265:H1249-56 pubmed
    We investigated the effect of the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and coformycin on high-energy phosphate metabolism, tissue nucleotides and nucleosides, and recovery of contractile function in ..
  22. Urba W, Baseler M, Kopp W, Steis R, Clark J, Smith J, et al. Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia. Blood. 1989;73:38-46 pubmed
    ..Six patients developed localized Herpes zoster infection among 21 patients who had received dCF. Pending the results of long-term follow-up, we recommend that dCF be reserved for patients who have failed splenectomy and IFN therapy. ..
  23. Johnson M, Johns D, Fridland A. 2',3'-Dideoxynucleoside phosphorylation by deoxycytidine kinase from normal human thymus extracts: activation of potential drugs for AIDS therapy. Biochem Biophys Res Commun. 1987;148:1252-8 pubmed
    ..Thus, dideoxynucleosides are activated by deoxycytidine kinase through a different catalytic interaction than occurs in 5'-activation of 3'-hydroxynucleosides by this enzyme. ..
  24. Balzarini J, Baba M, Pauwels R, Herdewijn P, Wood S, Robins M, et al. Potent and selective activity of 3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside, 3'-fluoro-2,6-diaminopurine-2',3'-dideoxyriboside, and 3'-fluoro-2',3'-dideoxyguanosine against human immunodeficiency virus. Mol Pharmacol. 1988;33:243-9 pubmed
    ..This suggests that ddDAPR and FddDAPR are primarily active as their guanine analogues, whereas AzddDAPR may be potentially active as a 2,6-diaminopurine derivative as well. ..
  25. O Dwyer P, King S, Eisenhauer E, Grem J, Hoth D. Hypersensitivity reactions to deoxycoformycin. Cancer Chemother Pharmacol. 1989;23:173-5 pubmed
    ..The value of dCF in treating lymphoid neoplasms suggests that further study of the treatment of these reactions is indicated. ..
  26. Bookser B, Kasibhatla S, Erion M. AMP deaminase inhibitors. 4. Further N3-substituted coformycin aglycon analogues: N3-alkylmalonates as ribose 5'-monophosphate mimetics. J Med Chem. 2000;43:1519-24 pubmed
    ..of the ribose 5'-monophosphate component of the very potent transition-state analogue AMPDA inhibitor coformycin monophosphate (1) with a simple alkylcarboxy group resulted in potent, selective, and cell-penetrating AMPDA ..
  27. Hanvey J, Hawkins E, Baker D, Suhadolnik R. 8-Ketodeoxycoformycin and 8-ketocoformycin as intermediates in the biosynthesis of 2'-deoxycoformycin and coformycin. Biochemistry. 1988;27:5790-5 pubmed
    ..and 8-ketocoformycin (8-ketoCoF) to the naturally occurring nucleoside analogues 2'-deoxycoformycin (dCF) and coformycin (CoF), respectively...
  28. Dearden C, Matutes E, Hoffbrand A, Ganeshaguru K, Brozovic M, Williams H, et al. Membrane phenotype and response to deoxycoformycin in mature T cell malignancies. Br Med J (Clin Res Ed). 1987;295:873-5 pubmed
    ..Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin. ..
  29. Ho A, Ganeshaguru K. Enzymes of purine metabolism in lymphoid neoplasms, clinical relevance for treatment with enzyme inhibitors. Klin Wochenschr. 1988;66:467-74 pubmed
    ..This review concerns the enzymatic make-up of normal and neoplastic lymphocytes and exploitation of this knowledge for the treatment of lymphomas. Special emphasis will be put on the clinical use of an ADA-inhibitor, deoxycoformycin. ..
  30. Copelan E, Johnson S, Grever M, Sheridan J, Tutschka P. Pharmacologic marrow purging in murine T cell leukemia. Blood. 1988;71:1656-61 pubmed
    ..This murine model provides information not available from in vitro assays and may be useful in the development of strategies to purge malignant T cells from marrow. ..
  31. Stepinski J, Pawelczyk T, Bizon D, Angielski S. Purine nucleotide cycle in rat renal cortex and medulla under conditions that mimic normal and low oxygen supply. Kidney Int. 1996;50:1195-201 pubmed
  32. Ho A, Ganeshaguru K, Knauf W, Dietz G, Trede I, Hunstein W, et al. Clinical response to deoxycoformycin in chronic lymphoid neoplasms and biochemical changes in circulating malignant cells in vivo. Blood. 1988;72:1884-90 pubmed
    ..The difference in inhibition of SAH-hydrolase was statistically significant (P = .0023). These results suggest that DNA strand breaks and inhibition of SAH-hydrolase correlate with clinical response. ..
  33. Dale N. Delayed production of adenosine underlies temporal modulation of swimming in frog embryo. J Physiol. 1998;511 ( Pt 1):265-72 pubmed
    ..This inhibition is a key determinant of the rate of run-down. ..
  34. Wen L, Knowles A. Extracellular ATP and adenosine induce cell apoptosis of human hepatoma Li-7A cells via the A3 adenosine receptor. Br J Pharmacol. 2003;140:1009-18 pubmed
    ..4. Cytotoxicity caused by exogenous ATP and adenosine was completely abolished by the caspase-3 inhibitor Z-DEVD-FMK, demonstrating the central role of caspase-3 in apoptosis of Li-7A cells. ..
  35. Ho J, Mohareb R, Ahn J, Sim T, Rapoport H. Enantiospecific synthesis of carbapentostatins. J Org Chem. 2003;68:109-14 pubmed
    ..Hydroboration and oxidation transform this compound stereospecifically into aminocyclopentanol 26, the key aminocyclitol component for an asymmetric synthesis of (+)-carbapentostatin. ..
  36. Brown D, Netting A, Chun B, Choi Y, Chu C, Gero A. L-nucleoside analogues as potential antimalarials that selectively target Plasmodium falciparum adenosine deaminase. Nucleosides Nucleotides. 1999;18:2521-32 pubmed
    The L-stereoisomer analogues of D-coformycin selectively inhibited P. falciparum adenosine deaminase (ADA) in the picomolar range (L-isocoformycin, Ki 7 pM; L-coformycin, Ki 250 pM)...
  37. Barry C, Lind S. Adenosine-mediated killing of cultured epithelial cancer cells. Cancer Res. 2000;60:1887-94 pubmed
    ..Similar effects were found when ATP, ADP, or AMP was substituted for Ado. Surprisingly, the ADA inhibitor coformycin (CF) had a much greater potentiating effect than did 2'-deoxycoformycin (DCF), although DCF is a more potent ADA ..
  38. Kline P, Schramm V. Electrostatic potential surfaces of the transition state for AMP deaminase and for (R)-coformycin, a transition state inhibitor. J Biol Chem. 1994;269:22385-90 pubmed
    ..transition state has been determined by molecular orbital calculations and compared to that of the base of (R)-coformycin 5'-monophosphate, a slow onset, tight binding inhibitor of AMP deaminase that binds with an overall dissociation ..
  39. Ganeshaguru K, Ho A, Piga A, Catovsky D, Hoffbrand A. Biochemical mechanisms of deoxycoformycin toxicity in chronic leukemias. Leuk Res. 1987;11:941-5 pubmed
    ..Although HCL responds particularly well to dCF in vivo, no difference in the in-vitro effects of dCF studied here could be detected between cases of HCL and the other types of chronic leukemia. ..
  40. Schwartz C, Minniti C, Harwood P, Na S, Banquerigo M, Strauss L, et al. Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. J Clin Oncol. 1987;5:1900-11 pubmed
    ..These results provide the basis for a clinical trial of bone marrow transplantation using combined pharmacologic/immunologic purging of T lymphoblasts from patients' harvested autologous marrow. ..
  41. Spiers A, Parekh S. The treatment of hairy cell leukemia with 2'-deoxycoformycin: results in India and in the United States. Leukemia. 1987;1:347-50 pubmed
    ..For hairy cell leukemia, pentostatin is a better treatment than splenectomy and probably is superior to interferon, but further studies are needed to better define its role in this disease. ..
  42. Rapoport I, Rapoport S, Gerber G. Degradation of AMP in erythrocytes of man. Evidence for a cytosolic phosphatase activity. Biomed Biochim Acta. 1987;46:317-29 pubmed
    ..Both AMP and IMP are dephosphorylated by an unspecific cytosolic acid phosphatase, the maximal activity of which amounts to 660 mumol nucleotide/l cells X h. ..
  43. Das D, Steinberg H. Adenosine transport by the lung. J Appl Physiol (1985). 1988;65:297-305 pubmed
    ..Uptake of [14C]adenosine remained unchanged when deamination of adenosine was inhibited by 8-azaguanine or coformycin. In a single passage of adenosine through the pulmonary artery, very little of the deaminated products appeared ..
  44. Schofer O, Veit B. [Modulation of graft versus host disease by in vitro incubation of donor cells with deoxycoformycin and deoxyadenosine]. Immun Infekt. 1987;15:186-90 pubmed
    ..However, GVHD could not be completely prevented by the in vitro treatment of donor cells. ..
  45. Johnston J, Eisenhauer E, Corbett W, Scott J, Zaentz S. Efficacy of 2'-deoxycoformycin in hairy-cell leukemia: a study of the National Cancer Institute of Canada Clinical Trials Group. J Natl Cancer Inst. 1988;80:765-9 pubmed
    ..We conclude that low-dose DCF is highly effective in treating hairy-cell leukemia. ..
  46. Caciagli F, Ciccarelli R, Di Iorio P, Ballerini P, Tacconelli L. Cultures of glial cells release purines under field electrical stimulation: the possible ionic mechanisms. Pharmacol Res Commun. 1988;20:935-47 pubmed
    ..These findings indicate that the frequency-dependent purine release from cultured glial cells is linked to ionic mechanisms, which calcium and potassium are mainly involved in. ..
  47. Winick N, Buchanan G, Murphy S, Yu A, Boyett J. Deoxycoformycin treatment for childhood T-cell acute lymphoblastic leukemia early in second remission: a Pediatric Oncology Group Study. Med Pediatr Oncol. 1988;16:327-32 pubmed
    ..DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T-cell lymphoblastic malignancies. ..
  48. Skubitz K, Wickham N, Hammerschmidt D. Endogenous and exogenous adenosine inhibit granulocyte aggregation without altering the associated rise in intracellular calcium concentration. Blood. 1988;72:29-33 pubmed
    ..Furthermore, the augmentation of responses seen with ADA suggests that endogenous adenosine may be a physiologic autocrine regulator of granulocyte function. ..
  49. Zoref Shani E, Kessler Icekson G, Sperling O. Pathways of adenine nucleotide catabolism in primary rat cardiomyocyte cultures. J Mol Cell Cardiol. 1988;20:23-33 pubmed
    ..The salvage of adenosine appeared to be efficient at physiological conditions, but not at fast rates of ATP degradation. ..
  50. Svendsen K, Overgaard Hansen K, Frederiksen S. Synergistic effect of 3'-deoxyadenosine N1-oxide and adenosine deaminase inhibitors on growth of Ehrlich ascites tumor cells in vivo. Cancer Chemother Pharmacol. 1988;21:35-9 pubmed
    ..The development of resistance to 3'-dANO was studied in cell cultures and found to be accompanied by changes in the enzyme activities of the reductase, the adenosine kinase, and the adenosine deaminase. ..
  51. Ho A, Grossmann M, Knauf W, Martin H, Trumper L, Zwingers T, et al. Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy. Leukemia. 1989;3:718-23 pubmed
    ..Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy. ..
  52. Peachell P, Columbo M, Kagey Sobotka A, Lichtenstein L, Marone G. Adenosine potentiates mediator release from human lung mast cells. Am Rev Respir Dis. 1988;138:1143-51 pubmed
    ..In total, these results suggest that the response of HLMC to adenosine describes properties most consistent with an A2/Ra-like process, although an interaction via an, as yet, uncharacterized cell surface receptor cannot be excluded. ..
  53. MacLeod R, Bryant P. Effects of adenine arabinoside and coformycin on the kinetics of G2 chromatid aberrations in X-irradiated human lymphocytes. Mutagenesis. 1992;7:285-90 pubmed
    ..However, in the presence of the ADA inhibitor coformycin, inhibition of break repair was already observed at an ara A concentration of 100 microM indicating that the ..