Summary: An anthrocycline from a Streptomyces nogalater variant. It is a cytolytic antineoplastic that inhibits DNA-dependent RNA synthesis by binding to DNA.

Top Publications

  1. Kapur A, Beck J, Sheil M. Observation of daunomycin and nogalamycin complexes with duplex DNA using electrospray ionisation mass spectrometry. Rapid Commun Mass Spectrom. 1999;13:2489-97 pubmed
    The noncovalent binding of the antitumour drugs daunomycin and nogalamycin to duplex DNA has been studied using electrospray ionisation mass spectrometry (ESI-MS)...
  2. Cruse W, Saludjian P, Leroux Y, Leger G, Manouni D, Prange T. A continuous transition from A-DNA to B-DNA in the 1:1 complex between nogalamycin and the hexamer dCCCGGG. J Biol Chem. 1996;271:15558-67 pubmed
    The antibiotic nogalamycin, a drug with high specificity for TG and CG steps in double-stranded DNA, has been crystallized as a 1:1 complex with the hexamer d(CCCGGG)...
  3. Ylihonko K, Hakala J, Kunnari T, M nts l P. Production of hybrid anthracycline antibiotics by heterologous expression of Streptomyces nogalater nogalamycin biosynthesis genes. Microbiology. 1996;142 ( Pt 8):1965-72 pubmed publisher
    ..lividans. The compound is derived from nogalonic acid methyl ester, an early intermediate in nogalamycin biosynthesis. Complementation with the cloned 12 kb fragment of S...
  4. Robinson H, Liaw Y, van der Marel G, van Boom J, Wang A. NMR studies on the binding of antitumor drug nogalamycin to DNA hexamer d(CGTACG). Nucleic Acids Res. 1990;18:4851-8 pubmed
    The interactions between a novel antitumor drug nogalamycin with the self-complementary DNA hexamer d(CGTACG) have been studied by 500 MHz two dimensional proton nuclear magnetic resonance spectroscopy...
  5. Torkkell S, Kunnari T, Palmu K, Mantsala P, Hakala J, Ylihonko K. The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: characterization of a 20-kb DNA region and generation of hybrid structures. Mol Genet Genomics. 2001;266:276-88 pubmed elucidate the molecular genetic basis of the biosynthetic pathway of the anthracycline antibiotic nogalamycin. Structural analysis of the products obtained by expression of the fragments in S. galilaeus and S...
  6. Smith C, Brannigan J, Moore M. Factors affecting DNA sequence selectivity of nogalamycin intercalation: the crystal structure of d(TGTACA)2-nogalamycin2. J Mol Biol. 1996;263:237-58 pubmed
    As part of an investigation into the sequence selectivity of the nogalamycin-DNA interaction, the 1.58 A structure of nogalamycin complexed with d5'(TGTACA)2 has been determined by single-crystal X-ray analysis...
  7. Claesson M, Siitonen V, Dobritzsch D, Metsä Ketelä M, Schneider G. Crystal structure of the glycosyltransferase SnogD from the biosynthetic pathway of nogalamycin in Streptomyces nogalater. FEBS J. 2012;279:3251-63 pubmed publisher
    ..during the final steps of biosynthesis of the aromatic polyketide nogalamycin. The crystal structure of recombinant SnogD, as an apo-enzyme and with a bound nucleotide, 2-deoxyuridine-5'-..
  8. Box V. The intercalation of DNA double helices with doxorubicin and nogalamycin. J Mol Graph Model. 2007;26:14-9 pubmed
    ..of the factors that could hold the intercalated entities like doxorubicin in place, but the bulky anthraquinone nogalamycin did not seem to become engaged in electron transfer...
  9. Williams L, Egli M, Qi G, Bash P, van der Marel G, van Boom J, et al. Structure of nogalamycin bound to a DNA hexamer. Proc Natl Acad Sci U S A. 1990;87:2225-9 pubmed
    The anthracycline antibiotic nogalamycin, which binds to DNA, is composed of a planar aglycone substituted on each end to form an unusual dumbbell-shaped molecule...

More Information


  1. Ray R, Chakraborty B, Ray K, Mukherji S, Chowdhury J, Panda C. Effect of anthracycline antitumor antibiotics (adriamycin and nogalamycin) and cycloheximide on the biosynthesis and processing of major UsnRNAs. Mol Cell Biochem. 1996;162:75-82 pubmed
    In the present study, anthracycline antitumor antibiotics (e.g. adriamycin and nogalamycin), the potent RNA synthesis inhibitors and cycloheximide, the protein synthesis inhibitor, have been used to understand the events of biosynthesis ..
  2. Larson E, Drummond J. Human mismatch repair and G*T mismatch binding by hMutSalpha in vitro is inhibited by adriamycin, actinomycin D, and nogalamycin. J Biol Chem. 2001;276:9775-83 pubmed
    ..We found that adriamycin, nogalamycin, and actinomycin D comprise a class of drugs that reversibly inhibits human mismatch repair in vitro at low ..
  3. Dodion P, de Valeriola D, Crespeigne N, Peeters B, Wery F, van Berchem C, et al. Phase I clinical and pharmacokinetic trial of oral menogaril administered on three consecutive days. Eur J Cancer Clin Oncol. 1988;24:1019-26 pubmed
  4. Boven E, Schluper H, Erkelens C, Pinedo H. Doxorubicin compared with related compounds in a nude mouse model for human ovarian cancer. Eur J Cancer. 1990;26:983-6 pubmed
    ..Compared with doxorubicin, mitoxantrone and menogaril were given in proportionally higher doses than those administered to patients, but did not result in superior antitumour activity. ..
  5. Long H, Laurie J, Wieand H, Edmonson J, Levitt R, Krook J, et al. A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic. Cancer. 1991;68:730-2 pubmed
    ..The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment. ..
  6. White C, Heidenreich O, Nordheim A, Beerman T. Evaluation of the effectiveness of DNA-binding drugs to inhibit transcription using the c-fos serum response element as a target. Biochemistry. 2000;39:12262-73 pubmed
    ..A(3) and Hoechst 33342, which bind to G/C-rich and A/T-rich regions, respectively, and the intercalating agent nogalamycin, which binds G/C-rich sequences in the major groove...
  7. Buckner J, Edmonson J, Ingle J, Schaid D. Evaluation of menogaril in patients with metastatic sarcomas and no prior chemotherapy exposure. Am J Clin Oncol. 1989;12:384-6 pubmed
    Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin...
  8. Ylihonko K, Tuikkanen J, Jussila S, Cong L, Mantsala P. A gene cluster involved in nogalamycin biosynthesis from Streptomyces nogalater: sequence analysis and complementation of early-block mutations in the anthracycline pathway. Mol Gen Genet. 1996;251:113-20 pubmed
    ..nogalater minimal PKS genes produced auramycinone glycosides, demonstrating replacement of the starter unit for polyketide biosynthesis. The product of snoA seems to be needed for expression of at least the genes for the minimal PKS. ..
  9. Fletcher M, Fox K. Visualising the dissociation of sequence selective ligands from individual binding sites on DNA. FEBS Lett. 1996;380:118-22 pubmed
    ..used a modification of the footprinting technique to measure the dissociation of mithramycin, echinomycin and nogalamycin from their binding sites in a natural DNA fragment...
  10. Mangiarotti G, Bulfone S, Giorda R, Morandini P, Ceccarelli A, Hames B. Analysis of specific mRNA destabilization during Dictyostelium development. Development. 1989;106:473-81 pubmed
    ..Destabilization of sensitive mRNAs is induced by cell dissociation even in the presence of concentrations of nogalamycin that inhibit RNA synthesis...
  11. Hauser F, Ganguly D. Synthetic studies on nogarol anthracyclines. Enantioselective total synthesis of an aminohydroxy epoxybenzoxocin. J Org Chem. 2000;65:1842-9 pubmed
    ..The 17-step sequence from the phenol 11 to 6 was achieved in 22% overall yield. ..
  12. Liaw Y, Gao Y, Robinson H, van der Marel G, van Boom J, Wang A. Antitumor drug nogalamycin binds DNA in both grooves simultaneously: molecular structure of nogalamycin-DNA complex. Biochemistry. 1989;28:9913-8 pubmed
    The three-dimensional molecular structures of the complexes between an interesting antitumor drug, nogalamycin, and two DNA hexamers, d[CGT(pS)ACG] and d[m5CGT(pS)Am5CG], were determined at high resolution by X-ray diffraction analyses...
  13. Skillings J, Cripps C, Eisenhauer E, Pater J, Verma S, Walde D. A phase II study of menogaril in low-grade non-Hodgkin's lymphoma. An NCI Canada Clinical Trials Group study. Invest New Drugs. 1991;9:79-82 pubmed
    ..Partial responses were seen in 9 patients (35%). Toxicity was moderate including myelosuppression, nausea, phlebitis, alopecia, and lethargy. This drug has only modest activity in this potentially responsive group of patients. ..
  14. Chiang S, Welch J, Rauscher F, Beerman T. Effect of DNA-binding drugs on early growth response factor-1 and TATA box-binding protein complex formation with the herpes simplex virus latency promoter. J Biol Chem. 1996;271:23999-4004 pubmed
    ..With the simultaneous addition of both EGR1 and TBP, the intercalator nogalamycin prevented EGR1 complex formation, resulting in a dose-dependent increase of the TBP.DNA complex...
  15. Yakovleva L, Handy C, Sayer J, Pirrung M, Jerina D, Shuman S. Benzo[c]phenanthrene adducts and nogalamycin inhibit DNA transesterification by vaccinia topoisomerase. J Biol Chem. 2004;279:23335-42 pubmed
    ..The anthracycline drug nogalamycin, a non-covalent intercalator with preference for 5'-TG dinucleotides, inhibited the single-turnover DNA ..
  16. Bichay T, Adams E, Inch W, Adams W, Brewer J, Bhuyan B. HPLC and flow cytometric analyses of uptake of adriamycin and menogaril by monolayers and multicell spheroids. Sel Cancer Ther. 1990;6:153-66 pubmed
    ..Thus, both techniques showed that at equal drug concentration in medium drug uptake in monolayers was much greater than in spheroids.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  17. Muggia F, Green M. New anthracycline antitumor antibiotics. Crit Rev Oncol Hematol. 1991;11:43-64 pubmed
    ..It is likely that these modifications will lead to an expanding therapeutic spectrum for these already widely useful drugs. ..
  18. Williams H, Searle M. Structure, dynamics and hydration of the nogalamycin-d(ATGCAT)2Complex determined by NMR and molecular dynamics simulations in solution. J Mol Biol. 1999;290:699-716 pubmed
    The structure of the 1:1 nogalamycin:d(ATGCAT)2 complex has been determined in solution from high-resolution NMR data and restrained molecular dynamics (rMD) simulations using an explicit solvation model...
  19. Sim S, Pilch D, Liu L. Site-specific topoisomerase I-mediated DNA cleavage induced by nogalamycin: a potential role of ligand-induced DNA bending at a distal site. Biochemistry. 2000;39:9928-34 pubmed
    Many DNA binding ligands (e.g., nogalamycin, actinomycin D, terbenzimidazoles, indolocarbazoles, nitidine, and coralyne) and various types of DNA lesions (e.g...
  20. van Houte L, van Garderen C, Patel D. The antitumor drug nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). Biochemistry. 1993;32:1667-74 pubmed
    The structures of the physical complex of d(GCGT).d(ACGC) with the anthracycline antitumor drug nogalamycin were studied in order to determine the sequence specificity and the drug orientation at the symmetric d(C2G3)...
  21. Searle M, Bicknell W. Interaction of the anthracycline antibiotic nogalamycin with the hexamer duplex d(5'-GACGTC)2. An NMR and molecular modelling study. Eur J Biochem. 1992;205:45-58 pubmed
    The interaction of the anthracycline antibiotic nogalamycin with the single 5'-CpG binding site at the centre of the hexamer duplex d(GACGTC)2 has been investigated in solution by NMR spectroscopy...
  22. White R, Phillips D. Bidirectional transcription footprinting of DNA binding ligands. Biochemistry. 1989;28:6259-69 pubmed
    ..footprinting with a series of DNA binding drugs [actinomycin D, echinomycin, bis(thiadaunomycin), mithramycin, nogalamycin, and an acridine-tripyrrole]...
  23. Ohashi K, Hara H, Takahashi F, Aso R, Akimoto T, Nakama K. [Pharmacokinetic studies of menogaril (TUT-7) with rats]. Gan To Kagaku Ryoho. 1992;19:1825-9 pubmed
    ..C.), the maximum plasma concentrations (Cmax) and AUC of both the unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over all elimination was slower in animals with liver dysfunction. ..
  24. Satoh H, Taguchi H, Yahagi S. [Antitumor spectrum of TUT-7 on rat ascitic hepatoma]. Gan To Kagaku Ryoho. 1990;17:287-91 pubmed
    ..A marked antitumor effect was observed in most tumor lines, and the activity was assumed to be better than adriamycin. ..
  25. Evstigneev M, Khomich V, Davies D. Complexation of anthracycline drugs with DNA in the presence of caffeine. Eur Biophys J. 2006;36:1-11 pubmed
    The competitive binding of anthracycline antitumour drugs, [daunomycin (DAU), doxorubicin (DOX) or nogalamycin (NOG)], with caffeine (CAF) to a model DNA oligomer has been investigated by 500 MHz 1H NMR spectroscopy under physiological ..
  26. Sim S, Gatto B, Yu C, Liu A, Li T, Pilch D, et al. Differential poisoning of topoisomerases by menogaril and nogalamycin dictated by the minor groove-binding nogalose sugar. Biochemistry. 1997;36:13285-91 pubmed
    ..We show that the nogalose sugar ring of nogalamycin, which binds to the minor groove of DNA, plays an important role in affecting topoisomerase-specific poisoning...
  27. Eisenhauer E, Pritchard K, Perrault D, Verma S, Pater J. Activity of intravenous menogaril in patients with previously untreated metastatic breast cancer. A National Cancer Institute of Canada Clinical Trials Group study. Invest New Drugs. 1990;8:283-7 pubmed
    ..We conclude menogaril is active in breast cancer and recommend that because it can be delivered in high doses orally, future trials in this disease should focus on intense oral schedule. ..
  28. Kantola J, Blanco G, Hautala A, Kunnari T, Hakala J, Mendez C, et al. Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline. Chem Biol. 1997;4:751-5 pubmed
    Mithramycin, nogalamycin and aclacinomycins are aromatic polyketide antibiotics that exhibit antitumour activity...
  29. Vance R, Crowley J, Macdonald J, Ahmann F. Phase II evaluation of menogaril (NSC-269148) in non-small cell lung carcinoma. A Southwest Oncology Group study. Invest New Drugs. 1991;9:73-5 pubmed
    ..Otherwise, the drug was reasonably well tolerated. At this dosage and schedule, menogaril has no substantial anti-tumor activity for patients with non-small cell lung cancer. ..
  30. Cruz J, Case L, Dalton H, Ramseur W, Richards F, Jackson D, et al. Menogaril in the treatment of relapsed multiple myeloma. A phase II trial of the Cancer Center of Wake Forest University. Invest New Drugs. 1992;10:35-7 pubmed
    ..The median progression-free interval was 3.0 months with a range of 0.7 to 22 months and median survival was 11.3 months with a range of 0.7 to 39+ months. Menogaril displays little activity in patients with previously treated MM. ..
  31. Sternberg C, Magill G, Cheng E, Hollander P. Phase II trial of menogarol in the treatment of advanced adenocarcinoma of the pancreas. Am J Clin Oncol. 1988;11:174-6 pubmed
    ..No patients responded. At this dosage and schedule, there is no role for menogarol in the treatment of advanced pancreatic adenocarcinoma. ..
  32. Kamiyama H, Rauenzahn S, Shim J, Karikari C, Feldmann G, Hua L, et al. Personalized chemotherapy profiling using cancer cell lines from selectable mice. Clin Cancer Res. 2013;19:1139-46 pubmed publisher
    ..Xenografts of this carcinoma were selectively responsive to both drugs. Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. ..
  33. George J, Ghate S, Matson S, Besterman J. Inhibition of DNA helicase II unwinding and ATPase activities by DNA-interacting ligands. Kinetics and specificity. J Biol Chem. 1992;267:10683-9 pubmed
    ..However, DNA intercalators, such as mitoxantrone and nogalamycin, which position functionalities in the major groove upon binding duplex DNA, were potent inhibitors of helicase ..
  34. Aaron C, Sorg R, Zimmer D. The mouse bone marrow micronucleus test: evaluation of 21 drug candidates. Mutat Res. 1989;223:129-40 pubmed
    ..The remaining 17 compounds were classified as negative in the assay. In general the results of the micronucleus test agreed with the results of other genetic toxicology assays on this group of compounds. ..
  35. Badiner G, Moy B, Smith K, Tarpley W, Groppi V, Bhuyan B. P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype. Br J Cancer. 1990;62:378-84 pubmed
    ..Therefore, we conclude that glutathione is not likely to be involved in menogaril resistance to P388/MEN cells. ..
  36. Torkkell S, Ylihonko K, Hakala J, Skurnik M, Mantsala P. Characterization of Streptomyces nogalater genes encoding enzymes involved in glycosylation steps in nogalamycin biosynthesis. Mol Gen Genet. 1997;256:203-9 pubmed
    The sno gene cluster in Streptomyces nogalater ATCC 27451 contains the nogalamycin biosynthesis genes. A set of plasmid constructions carrying fragments of the sno cluster that lie downstream of snoD were used to complement the S...
  37. Suh D, Oh Y, Ahn B, Hur M, Kim H, Lee M, et al. Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence. Exp Mol Med. 2002;34:326-31 pubmed
    ..DNA cleavage occurred at about 1% by the increments of 1 micromM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process. ..
  38. Ohe Y, Nakagawa K, Fujiwara Y, Sasaki Y, Minato K, Bungo M, et al. In vitro evaluation of the new anticancer agents KT6149, MX-2, SM5887, menogaril, and liblomycin using cisplatin- or adriamycin-resistant human cancer cell lines. Cancer Res. 1989;49:4098-102 pubmed
    ..However, K562/ADM was 2.4-fold more sensitive to CDDP than its parental cell line, K562 (P less than 0.001). These results suggested that the mechanism of CDDP resistance is different from that of multidrug resistance. ..
  39. Searle M, Lane A. 31P NMR investigation of the backbone conformation and dynamics of the hexamer duplex d(5'-GCATGC)2 in its complex with the antibiotic nogalamycin. FEBS Lett. 1992;297:292-6 pubmed
    ..shift correlation experiments confirm that the two down-field shifted 31P resonances in the spectrum of the (nogalamycin)2-d(GCATGC)2 complex correspond to the phosphodiesters CpA and TpG at the intercalation sites...
  40. Robinson H, Yang D, Wang A. Structure and dynamics of the antitumor drugs nogalamycin and disnogalamycin complexed to d(CGTACG)2: comparison of crystal and solution structures. Gene. 1994;149:179-88 pubmed
    The nuclear magnetic resonance (NMR) solution structures of the 2:1 complexes of nogalamycin-d(CGTACG)2 (Ng-CGTACG) and disnogalamycin-d(CGTACG)2 (DNg-CGTACG) have been determined by a quantitative treatment of two-dimensional nuclear ..
  41. Stephens R, Goodman P, Crawford E, Spicer C, Lowe B, Ahmann F, et al. Evaluation of menogaril in renal cell carcinoma. A Southwest Oncology Group phase II study (8504). Invest New Drugs. 1990;8 Suppl 1:S69-71 pubmed
    ..No cardiac toxicity was noted. The low response rate suggests that menogaril in this dose schedule has no role in the treatment of patients with advanced metastatic renal cancer. ..
  42. Egorin M, Conley B, Forrest A, Zuhowski E, Sinibaldi V, Van Echo D. Phase I study and pharmacokinetics of menogaril (NSC 269148) in patients with hepatic dysfunction. Cancer Res. 1987;47:6104-10 pubmed
    ..On the other hand, there was no difference in the relationship between percentage decrease in neutrophils and menogaril area under the curve in these two groups of patients.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  43. Nasirudin K, Ehtesham N, Tuteja R, Sopory S, Tuteja N. The Gly-Arg-rich C-terminal domain of pea nucleolin is a DNA helicase that catalytically translocates in the 5'- to 3'-direction. Arch Biochem Biophys. 2005;434:306-15 pubmed
    ..The anti-nucleolin antibodies immunodepleted the activities of the enzyme. The DNA interacting ligands nogalamycin, daunorubicin, actinomycin C1, and ethidium bromide were inhibitory to DNA unwinding (with K(i) values of 0...
  44. Caceres Cortes J, Wang A. Binding of the antitumor drug nogalamycin to bulged DNA structures. Biochemistry. 1996;35:616-25 pubmed
    ..Binding of the anthracycline antitumor antibiotic nogalamycin (Ng) to these two heptamers stabilizes the duplex structure...
  45. Metsä Ketelä M, Palmu K, Kunnari T, Ylihonko K, Mäntsälä P. Engineering anthracycline biosynthesis toward angucyclines. Antimicrob Agents Chemother. 2003;47:1291-6 pubmed
    The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster...
  46. Ishii Y, Ikushima T. Post-treatment effects of DNA topoisomerase inhibitors on UVB- and X-ray-induced chromosomal aberration formations. Mutat Res. 2002;504:67-74 pubmed
    Post-treatments with nogalamycin, an inhibitor of DNA topoisomerase I, for last 3h of the culture (during the G2 phase) drastically enhanced the yield of ultraviolet light B (UVB)-induced exchange-type chromatid aberrations, while ..
  47. Yun S, Dardik A, Haga M, Yamashita A, Yamaguchi S, Koh Y, et al. Transcription factor Sp1 phosphorylation induced by shear stress inhibits membrane type 1-matrix metalloproteinase expression in endothelium. J Biol Chem. 2002;277:34808-14 pubmed
  48. Kunnari T, Tuikkanen J, Hautala A, Hakala J, Ylihonko K, Mantsala P. Isolation and characterization of 8-demethoxy steffimycins and generation of 2,8-demethoxy steffimycins in Streptomyces steffisburgensis by the nogalamycin biosynthesis genes. J Antibiot (Tokyo). 1997;50:496-501 pubmed
    ..The genes encoding the polyketide ketoreductase and aromatase enzymes of nogalamycin biosynthesis caused the production of 2-demethoxy steffimycins in S. steffisburgensis.
  49. Kennedy M, Donehower R, Grochow L, Ettinger D, Fetting J, Abeloff M. Phase II trial of menogaril as initial chemotherapy for metastatic breast cancer. Invest New Drugs. 1990;8:289-94 pubmed
    ..Mean survival in all patients entered was 15.8 months from date of entry. Menogaril at this dose and schedule has modest activity as first line therapy for metastatic breast cancer but also has significant marrow and local toxicity. ..
  50. Smith C, Davies G, Dodson E, Moore M. DNA-nogalamycin interactions: the crystal structure of d(TGATCA) complexed with nogalamycin. Biochemistry. 1995;34:415-25 pubmed
    The structure of the self-complementary deoxyoligonucleotide d5'(TGATCA) complexed with nogalamycin, an antitumor anthracycline, has been solved to 1.8 A resolution using X-ray crystallographic methods...
  51. Phan T, Ehtesham N, Tuteja R, Tuteja N. A novel nuclear DNA helicase with high specific activity from Pisum sativum catalytically translocates in the 3'-->5' direction. Eur J Biochem. 2003;270:1735-45 pubmed
    ..The DNA intercalating agents actinomycin C1, ethidium bromide, daunorubicin and nogalamycin inhibit the DNA unwinding activity of PDH120 with Ki values of 5.6, 5.2, 4.0 and 0.71 micro Ms, respectively...
  52. Li L, Krueger W. The biochemical pharmacology of nogalamycin and its derivatives. Pharmacol Ther. 1991;51:239-55 pubmed
    This review assimilates up-to-date information on the biochemical pharmacology of nogalamycin and selected derivatives that have shown good biological activities and/or received a relatively detailed investigation...
  53. Williams L, Gao Q. DNA-ditercalinium interactions: implications for recognition of damaged DNA. Biochemistry. 1992;31:4315-24 pubmed
    ..comparison of the three-dimensional structure of the DNA-ditercalinium complex with those of triostin A and nogalamycin (chemotherapeutic agents that act by conventional mechanisms) allows us to suggest a general model for ..
  54. Fox K. Footprinting studies on the interactions of nogalamycin, arugomycin, decilorubicin and viriplanin with DNA. Anticancer Drug Des. 1988;3:157-68 pubmed
    DNase I footprinting studies employing several DNA fragments have confirmed that nogalamycin binds preferentially to regions of DNA containing alternating purines and pyrimidines...
  55. Keller K, Zhang J, Oehlers L, Brodbelt J. Influence of initial charge state on fragmentation patterns for noncovalent drug/DNA duplex complexes. J Mass Spectrom. 2005;40:1362-71 pubmed
    ..employed, in addition to an array of known DNA-interactive ligands, including the intercalators daunomycin and nogalamycin, as well as the minor groove binding agents distamycin, netropsin, 4',6-diamidino-2-phenylindole, and Hoechst ..
  56. Ettinger D, Finkelstein D, Abeloff M, Skeel R, Stott P, Frontiera M, et al. Justification for evaluating new anticancer drugs in selected untreated patients with extensive-stage small-cell lung cancer: an Eastern Cooperative Oncology Group randomized study. J Natl Cancer Inst. 1992;84:1077-84 pubmed
    ..The data do suggest, however, that use of this study design may have no adverse effect on survival. ..
  57. Tuteja N, Phan T, Tuteja R, Ochem A, Falaschi A. Inhibition of DNA unwinding and ATPase activities of human DNA helicase II by chemotherapeutic agents. Biochem Biophys Res Commun. 1997;236:636-40 pubmed
    ..We have determined the effect of actinomycin C1, VP-16, camptothecin, ethidium bromide, ellipticine, nogalamycin, novobiocin, genistein, m-AMSA, aphidicolin and daunorubicin on the enzymatic activities of purified human DNA ..
  58. Searle M, Wakelin L. Conformation and dynamics of the deoxyribose rings of a (nogalamycin)2-d (5'-GCATGC)2 complex studied in solution by 1H-n.m.r. spectroscopy. Biochem J. 1990;269:341-6 pubmed
    The conformation and dynamics of the deoxyribose rings of a (nogalamycin)2-d(5'-GCATGC)2 complex have been determined from an analysis of 1H-1H vicinal coupling constants and sums of coupling constants (J1'-2',J1'-2",epsilon 1', ..
  59. Holdener E, ten Bokkel Huinink W, Decoster G, Ludwig C, Renard G, Pinedo H. Phase II trial of menogaril in advanced colorectal cancer. Invest New Drugs. 1988;6:227-30 pubmed
    ..Nausea/vomiting (66%) and alopecia (50%) were. of mild-moderate degree. This study suggests that menogaril at these doses and schedule had no activity in advanced colorectal cancer. ..
  60. Long H, Wieand H, Foley J, Niedringhaus R, Laurie J, Morton R, et al. Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. Invest New Drugs. 1991;9:349-51 pubmed
  61. Wierzba K, Sugimoto Y, Matsuo K, Toko T, Takeda S, Yamada Y, et al. Menogaril, an anthracycline compound with a novel mechanism of action: cellular pharmacology. Jpn J Cancer Res. 1990;81:842-9 pubmed
    ..It was found that menogaril inhibited the initial polymerization rate of tubulin, indicating a possible contribution of this process to the overall cytotoxicity of menogaril. ..
  62. Siitonen V, Claesson M, Patrikainen P, Aromaa M, Mäntsälä P, Schneider G, et al. Identification of late-stage glycosylation steps in the biosynthetic pathway of the anthracycline nogalamycin. Chembiochem. 2012;13:120-8 pubmed publisher
    b>Nogalamycin is an anthracycline antibiotic that has been shown to exhibit significant cytotoxicity...
  63. Stewart D, Aitken S, Verma S, Maroun J, Robillard L, Touchie M, et al. Phase I study of oral menogaril administered daily for 14 consecutive days. Ann Oncol. 1992;3:401-3 pubmed
    ..Phase II studies are recommended in carcinoma of the bladder. Gastrointestinal toxicity is substantially less on this schedule than with oral menogaril administered on a weekly or q4wk schedule, but thrombocytopenia may be more common. ..
  64. Beinker P, Lohkamp B, Peltonen T, Niemi J, Mäntsälä P, Schneider G. Crystal structures of SnoaL2 and AclR: two putative hydroxylases in the biosynthesis of aromatic polyketide antibiotics. J Mol Biol. 2006;359:728-40 pubmed
    SnoaL2 and AclR are homologous enzymes in the biosynthesis of the aromatic polyketides nogalamycin in Streptomyces nogalater and cinerubin in Streptomyces galilaeus, respectively...
  65. Long H, Schaid D, Schutt A, Ingle J, Loprinzi C, Edmonson J. Phase II evaluation of menogaril in women with metastatic breast cancer after failure of first-line chemotherapy. Am J Clin Oncol. 1988;11:524-7 pubmed
    ..Failure to respond to menogaril does not preclude response to subsequent treatment with doxorubicin. ..
  66. Egli M, Williams L, Frederick C, Rich A. DNA-nogalamycin interactions. Biochemistry. 1991;30:1364-72 pubmed
    The anthracycline antibiotic nogalamycin differs from the more common daunomycin-type anthracyclines by substitution on both ends of the intercalating chromophore, giving nogalamycin the approximate shape of a dumbbell...
  67. Siitonen V, Blauenburg B, Kallio P, Mäntsälä P, Metsä Ketelä M. Discovery of a two-component monooxygenase SnoaW/SnoaL2 involved in nogalamycin biosynthesis. Chem Biol. 2012;19:638-46 pubmed publisher
    b>Nogalamycin is an anthracycline polyketide antibiotic that contains two deoxysugars, at positions C-1 and C-7...
  68. Welch J, Rauscher F, Beerman T. Targeting DNA-binding drugs to sequence-specific transcription factor.DNA complexes. Differential effects of intercalating and minor groove binding drugs. J Biol Chem. 1994;269:31051-8 pubmed
    ..Their DNA recognition sites include G/C-rich, mixed, and A/T-rich sequences. The intercalators nogalamycin and hedamycin, and the G/C-specific minor groove binding drug chromomycin A3 were the most potent drugs, ..
  69. Zhang X, Patel D. Solution structure of the nogalamycin-DNA complex. Biochemistry. 1990;29:9451-66 pubmed
    The nogalamycin-d(A-G-C-A-T-G-C-T) complex (two drugs per duplex) has been generated in aqueous solution and its structure characterized by a combined application of two-dimensional NMR experiments and molecular dynamics calculations...
  70. Piehler J, Brecht A, Gauglitz G, Maul C, Grabley S, Zerlin M. Specific binding of low molecular weight ligands with direct optical detection. Biosens Bioelectron. 1997;12:531-8 pubmed
    ..The four structurally different intercalators showed significant distinction in binding kinetics and equilibrium signals. Improvement of experimental parameters is required to obtain more reliable kinetic data. ..
  71. Harper A, Brannigan J, Buck M, Hewitt L, Lewis R, Moore M, et al. Structure of d(TGCGCA)2 and a comparison to other DNA hexamers. Acta Crystallogr D Biol Crystallogr. 1998;54:1273-84 pubmed
    ..A prediction of the water structure is compared with the observed pattern in the reported structure. ..
  72. Long H, Hauge M, Therneau T, Buckner J, Frytak S, Hahn R. Phase II evaluation of menogaril in patients with advanced hypernephroma. Invest New Drugs. 1991;9:261-2 pubmed
    ..Platelet toxicity was negligible. Venous irritation and phlebitis at the infusion site was seen in 47% of patients. Menogaril as administered in this protocol is ineffective in advanced renal cell carcinoma. ..
  73. Tuteja N, Phan T, Tewari K. Purification and characterization of a DNA helicase from pea chloroplast that translocates in the 3'-to-5' direction. Eur J Biochem. 1996;238:54-63 pubmed
    ..However, it fails to act on a blunt-ended 17-bp duplex DNA. The enzyme moves unidirectionally from 3' to 5' along the bound strand. The unwinding activity is inhibited by the intercalating drugs nogalamycin and daunorubicine.
  74. Sultana A, Kallio P, Jansson A, Wang J, Niemi J, Mäntsälä P, et al. Structure of the polyketide cyclase SnoaL reveals a novel mechanism for enzymatic aldol condensation. EMBO J. 2004;23:1911-21 pubmed
    ..The crystal structure of SnoaL, involved in nogalamycin biosynthesis, with a bound product, has been determined to 1.35 A resolution...
  75. White R, Phillips D. Sequence-dependent termination of bacteriophage T7 transcription in vitro by DNA-binding drugs. Biochemistry. 1989;28:4277-83 pubmed
    ..drugs with relatively long DNA residence times (half-life greater than or equal to 300 s at 20 degrees C for nogalamycin, actinomycin, mithramycin, and echinomycin) but to a lesser extent with drugs of intermediate residence times [..
  76. Kallio P, Sultana A, Niemi J, Mäntsälä P, Schneider G. Crystal structure of the polyketide cyclase AknH with bound substrate and product analogue: implications for catalytic mechanism and product stereoselectivity. J Mol Biol. 2006;357:210-20 pubmed
    ..and mechanism to the polyketide cyclase SnoaL that catalyses the corresponding reaction in the biosynthesis of nogalamycin. Similarity is also apparent at a functional level as AknH can convert nogalonic acid methyl ester, the natural ..
  77. Pham X, Tuteja N. Potent inhibition of DNA unwinding and ATPase activities of pea DNA helicase 45 by DNA-binding agents. Biochem Biophys Res Commun. 2002;294:334-9 pubmed
    ..the effect of various DNA-binding agents, such as daunorubicin, ethidium bromide, ellipticine, cisplatin, nogalamycin, actinomycin C1, and camptothecin on the DNA unwinding and ATPase activities of the plant nuclear DNA helicase ..
  78. Banerjee T, Mukhopadhyay R. Structural effects of nogalamycin, an antibiotic antitumour agent, on DNA. Biochem Biophys Res Commun. 2008;374:264-8 pubmed publisher
    The structural changes of DNA, induced by the antitumour antibiotic nogalamycin, have been studied by atomic force microscopy (AFM)...
  79. Rafty L, Khachigian L. Sp1 phosphorylation regulates inducible expression of platelet-derived growth factor B-chain gene via atypical protein kinase C-zeta. Nucleic Acids Res. 2001;29:1027-33 pubmed
    ..The anthracycline nogalamycin has previously been reported to inhibit the capacity of Egr-1 to bind DNA in vitro...
  80. Stewart D, Eisenhauer E, Skillings J, Pritchard K, Buckman R, Vandenberg T, et al. Phase II study of oral menogaril as first line chemotherapy for advanced breast cancer: a National Cancer Institute of Canada Clinical Trials Group study. Ann Oncol. 1992;3:201-4 pubmed
    ..In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer. ..
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  82. Torkkell S, Kunnari T, Palmu K, Hakala J, Mantsala P, Ylihonko K. Identification of a cyclase gene dictating the C-9 stereochemistry of anthracyclines from Streptomyces nogalater. Antimicrob Agents Chemother. 2000;44:396-9 pubmed
    b>Nogalamycin is an anthracycline antibiotic produced by Streptomyces nogalater. Its aglycone has a unique stereochemistry (7S, 9S, 10R) compared to that of most other anthracyclines (7S, 9R, 10R)...