Готові списки джерел за темами / KP1019

Добірка наукової літератури з теми "KP1019"

Автор: Grafiati
Опубліковано: 10 грудня 2022
Оновлено: 20 лютого 2023

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Статті в журналах з теми "KP1019"

1

Alessio, Enzo, and Luigi Messori. "NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry." Molecules 24, no. 10 (May 24, 2019): 1995. http://dx.doi.org/10.3390/molecules24101995.

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NAMI-A ((ImH)[trans-RuCl4(dmso-S)(Im)], Im = imidazole) and KP1019/1339 (KP1019 = (IndH)[trans-RuCl4(Ind)2], Ind = indazole; KP1339 = Na[trans-RuCl4(Ind)2]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates. This has led to a considerable amount of studies on their respective chemico-biological features and to the eventual admission of both to clinical trials. The encouraging pharmacological performances qualified KP1019 mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers, whereas the non-cytotoxic NAMI-A has gained the reputation of being a very effective antimetastatic drug. A critical and strictly comparative analysis of the studies conducted so far on NAMI-A and KP1019 allows us to define the state of the art of these experimental ruthenium drugs in terms of the respective pharmacological profiles and potential clinical applications, and to gain some insight into the inherent molecular mechanisms. Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium complexes form an exemplary and unique case in the field of medicinal inorganic chemistry.
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2

Heffeter, Petra, Katharina Böck, Bihter Atil, Mir Ali Reza Hoda, Wilfried Körner, Caroline Bartel, Ute Jungwirth, et al. "Intracellular protein binding patterns of the anticancer ruthenium drugs KP1019 and KP1339." JBIC Journal of Biological Inorganic Chemistry 15, no. 5 (March 11, 2010): 737–48. http://dx.doi.org/10.1007/s00775-010-0642-1.

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3

Stultz, Laura K., Alexandra Hunsucker, Sydney Middleton, Evan Grovenstein, Jacob O’Leary, Eliot Blatt, Mary Miller, James Mobley, and Pamela K. Hanson. "Proteomic analysis of the S. cerevisiae response to the anticancer ruthenium complex KP1019." Metallomics 12, no. 6 (2020): 876–90. http://dx.doi.org/10.1039/d0mt00008f.

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4

Bergamo, A., A. Masi, M. A. Jakupec, B. K. Keppler, and G. Sava. "Inhibitory Effects of the Ruthenium Complex KP1019 in Models of Mammary Cancer Cell Migration and Invasion." Metal-Based Drugs 2009 (September 17, 2009): 1–9. http://dx.doi.org/10.1155/2009/681270.

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The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects. The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development. These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.
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5

Kuhn, P. S., V. Pichler, A. Roller, M. Hejl, M. A. Jakupec, W. Kandioller, and B. K. Keppler. "Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential." Dalton Transactions 44, no. 2 (2015): 659–68. http://dx.doi.org/10.1039/c4dt01645a.

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NKP-1339 and KP1019 derivatives were synthesized under mild reaction settings in high yields. The characterization and influence of the N-alkyl substitution on the aqueous stability, redox potentials, in vitro cytotoxicity and cellular accumulation are discussed.
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6

Cirri, Damiano, Tiziano Marzo, Iogann Tolbatov, Alessandro Marrone, Francesco Saladini, Ilaria Vicenti, Filippo Dragoni, Adele Boccuto, and Luigi Messori. "In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study." Biomolecules 11, no. 12 (December 10, 2021): 1858. http://dx.doi.org/10.3390/biom11121858.

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Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl3), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl3, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.
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7

Levina, Aviva, Anthony R. M. Chetcuti, and Peter A. Lay. "Controversial Role of Transferrin in the Transport of Ruthenium Anticancer Drugs." Biomolecules 12, no. 9 (September 18, 2022): 1319. http://dx.doi.org/10.3390/biom12091319.

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Ruthenium complexes are at the forefront of developments in metal-based anticancer drugs, but many questions remain open regarding their reactivity in biological media, including the role of transferrin (Tf) in their transport and cellular uptake. A well-known anticancer drug, KP1019 ((IndH)[RuIIICl4(Ind)2], where Ind = indazole) and a reference complex, [RuIII(nta)2]3− (nta = nitrilotriacetato(3−)) interacted differently with human apoTf, monoFeTf, or Fe2Tf. These reactions were studied by biolayer interferometry (BLI) measurements of Ru–Fe–Tf binding to recombinant human transferrin receptor 1 (TfR1) in conjunction with UV-vis spectroscopy and particle size analysis. Cellular Ru uptake in human hepatoma (HepG2) cells was measured under the conditions of the BLI assays. The mode of Tf binding and cellular Ru uptake were critically dependent on the nature of Ru complex, availability of Fe(III) binding sites of Tf, and the presence of proteins that competed for metal binding, particularly serum albumin. Cellular uptake of KP1019 was not Tf-mediated and occurred mostly by passive diffusion, which may also be suitable for treatments of inoperable cancers by intratumoral injections. High cellular Ru uptake from a combination of [RuIII(nta)2]3− and Fe2Tf in the absence of significant Ru–Tf binding was likely to be due to trapping of Ru(III) species into the endosome during TfR1-mediated endocytosis of Fe2Tf.
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8

Juszczak, Michał, Magdalena Kluska, Daniel Wysokiński, and Katarzyna Woźniak. "Anti-cancer properties of ruthenium compounds: NAMI-A and KP1019." Postępy Higieny i Medycyny Doświadczalnej 74 (February 19, 2020): 12–19. http://dx.doi.org/10.5604/01.3001.0013.8549.

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Cancer research is among the key challenges in current medicine and biology. Many decades of investigations have brought measurable benefits in both areas with regard to expanding the knowledge of the molecular mechanism of cancer and developing treatment strategies. Despite that cancers are still among diseases with the highest mortality rate, and cancer treatment is often unsuccessful and connected with severe side effects. The development of therapeutic strategies in both targeting the primary tumor origin and preventing metastasis is largely based on testing newly synthesized chemical agents, including a group of metal-containing complexes. It seems that ruthenium-containing complexes are of high potential in cancer therapy, and our work presents the current data about the application of ruthenium-based complexes − NAMI-A and KP1019 in cancer therapy.
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9

Gransbury, Gemma K., Peter Kappen, Chris J. Glover, James N. Hughes, Aviva Levina, Peter A. Lay, Ian F. Musgrave, and Hugh H. Harris. "Comparison of KP1019 and NAMI-A in tumour-mimetic environments." Metallomics 8, no. 8 (2016): 762–73. http://dx.doi.org/10.1039/c6mt00145a.

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10

Heffeter, P., M. A. Jakupec, M. Pongratz, P. Chiba, M. Micksche, W. Körner, M. Hauses, B. Marian, B. K. Keppler, and W. Berger. "630 Molecular mechanisms of resistance against the ruthenium compound KP1019." European Journal of Cancer Supplements 2, no. 8 (September 2004): 190–91. http://dx.doi.org/10.1016/s1359-6349(04)80638-4.

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Дисертації з теми "KP1019"

1

O'Riley, Hannah Adele. "Mechanisms of the Anti-Metastatic and Cytotoxic Properties of Ruthenium Anti-Cancer Drugs." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/13881.

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Despite significant advances in the treatment of primary tumours through radiotherapy, surgery and chemotherapy; treatment and prevention of metastasis remains problematic. The benefits that traditional Pt chemotherapies have had on patient outcomes have been hampered by drug resistance and severe patient side-effects. These disadvantages have spurred fresh research into other metal-based pharmaceuticals and Ru complexes have been identified as promising drugs for cancer therapy. In this work, the mechanism of action of NAMI-A, KP1019 and other Ru complexes were investigated. A series of RuII complexes containing neutral face-capping sulfur macrocycle ligands, 1,4,7-trithiacyclononane ([9]aneS3), and 1,4,7,10-tetrathiacyclododecane ([12]aneS4) were synthesized, characterized and investigated to determine the significance of the kinetically driven activity of Ru drugs. As these Ru complexes ([RuCl2([9]aneS3)(S-dmso)], [RuBr2([9]aneS3)(S-dmso)], and [RuCl([12]aneS4)(S-dmso)]Cl) have structural similarities, relationships between the kinetic rates of halido ligand substitution (determined by UV-vis spectroscopy) and in vitro activity were established. The ligand 1,4,7-trimethyltriazacyclononane (Me3tacn), is a neutral face capped ligand investigated in this work. The reactivity and biological activity of the RuII/III trimer complex [Ru3Br6(Me3tacn)2]Br was studied. Previous studies have shown that Ru complexes such as NAMI-A and KP1019 behave as pro-drugs, and that their interaction with blood serum proteins is essential to their activity. Structural properties of the adducts of Ru with various serum proteins were revealed with the use X-ray absorption spectroscopy. The nature of Ru interaction with serum proteins was investigated with gel electrophoresis X-ray fluorescence mapping. This work provided insight into the nature of the reactions that occur when Ru pro-drugs are administered intravenously, and the results of these interactions on anti-cancer activity.
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2

Thomé, Isis Pires. "Síntese, caracterização e avaliação da atividade citotóxica de Indazolium trans[tetrachlorobis (1H-indazole) ruthenate (III)] (KP1019) em células de carcinoma mamário." reponame:Repositório Institucional da UnB, 2016. http://repositorio.unb.br/handle/10482/21255.

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Dissertação (mestrado)–Universidade de Brasília, Universidade UnB de Planaltina, Programa de Pós-Graduação em Ciência de Materiais, 2016.
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O câncer é uma doença muito agressiva que atinge milhões de pessoas no mundo. Entre os vários tipos de câncer, o carcinoma mamário é o segundo mais frequente no mundo e o que mais acomete as mulheres. A quimioterapia é uma abordagem terapêutica bastante empregada, especialmente no caso de doença metastática. Contudo, este tipo de tratamento apresenta limitações como falta de especificidade às células tumorais e ocorrência de quimioresistência. Por isso, faz-se necessário o desenvolvimento de tratamentos mais eficazes contra esta doença. Com o objetivo de melhorar a eficácia da quimioterapia para aumentar a expectativa de vida dos pacientes, várias propostas têm sido sugeridas. Os complexos metálicos vêm se mostrando agentes antitumorais promissores. Dentre eles, os complexos de Rutênio (Ru), como o KP1019, têm se destacado, pois apresentam (1) capacidade em se ligar à biomoléculas como transferrina; (2) considerável labilidade química; (3) atuação em células que desenvolveram resistência à cisplatina e (4) capacidade em participar de reações de oxirredução permitindo a existência dos mais importantes estados de oxidação em meio biológico. No presente trabalho, foi realizada a síntese do KP1019 e sua caracterização por ressonância magnética nuclear (RMN). Além disso, avaliou-se o efeito citotóxico deste complexo em células murinas de carcinoma mamário (4T1) e normais de fibroblastos (NIH-3T3). A citotoxicidade do KP1019 foi avaliada por testes de viabilidade celular por meio do método colorimétrico de MTT. As células foram tratadas com doses que variaram de 1,25 a 200 μM de KP1019 e cisplatina por períodos de 24, 48 e 72 horas. O KP1019 foi sintetizado e depois caracterizado por RMN e avaliado quanto à sua toxicidade. Após 24 h de tratamento, KP1019 induziu citotoxicidade semelhante à cisplatina em ambas as linhagens celulares. Além disso, notou-se que as linhagens 4T1 e NIH-3T3 tiveram a mesma sensibilidade ao tratamento com KP1019. No período de 48 horas, o KP1019 induziu diferente citotoxicidade nas duas linhagens, sendo que este não apresentou citotoxicidade para 4T1, enquanto que a cisplatina foi mais citotóxica para esta linhagem (doses acima de 12,5 μM). Em contrapartida, o KP1019 foi mais citotóxico para NIH-3T3 em doses a partir de 25 μM. Já no período de 72 horas, ambos os complexos foram similarmente citotóxicos em ambas as linhagens celulares a partir das doses 12,5 μM. Além disso, o efeito citotóxico de KP1019 e cisplatina foram diferentes na linhagem 4T1 (doses 1,25 e 2,5 μM). Ademais, a morfologia das células 4T1 foi analisada em microscópio óptico após tratamento por 24 horas com 20 μM de KP1019 ou cisplatina (IC50) e observou-se várias alterações relacionadas à citotoxicidade como arredondamento das células e aumento na quantidade de vesículas citoplasmáticas. Dessa forma, sugere-se que o efeito citotóxico de KP1019 foi dependente da dose, linhagem celular e tempo avaliados e, esta citotoxicidade está associada a alterações morfológicas provenientes de processo de morte celular, o que reforça o excelente potencial de KP1019 para uso na quimioterapia do câncer de mama. ________________________________________________________________________________________________ ABSTRACT
Cancer is a very aggressive disease that affects millions of people worldwide. Among the various types of cancer, breast cancer is the second most frequent in the world and that most affects women. Chemotherapy is fairly a therapeutic approach employed, particularly for metastatic disease. However, this treatment has limitations such as lack of specificity for tumor cells and occurrence of chemoresistance. Therefore, it is necessary to develop more effective treatments for this disease. In order to improve the effectiveness of chemotherapy to increase the life expectancy of patients, various proposals have been suggested. The metal complexes have shown to be promising antitumor agents. Among them, the complexes of ruthenium (Ru) as the KP1019, have been highlighted as present (1) the ability to bind to biomolecules such as transferrin; (2) substantial chemical lability; (3) operating in cells that have developed resistance to cisplatin and (4) the ability to participate in redox reactions allowing the existence of the most important oxidation states in biological medium. In the present work, the synthesis of KP1019 and its characterization by nuclear magnetic resonance imaging was performed (NMR). In addition, it evaluated the cytotoxic effect of this complex on murine mammary carcinoma cells (4T1) and normal fibroblasts (NIH-3T3). The cytotoxicity of KP1019 was evaluated by cell viability tests using the MTT colorimetric method. Cells were treated with doses ranging from 1.25 to 200 mM of KP1019 and cisplatin for periods of 24, 48 and 72 hours. The KP1019 was synthesized and then characterized by NMR and evaluated for their toxicity. After 24 h of treatment, KP1019 induced cytotoxicity similar to cisplatin in both cell lines. Furthermore, it was observed that the 4T1 and NIH-3T3 lines showed the same sensitivity to treatment with KP1019. Within 48 hours, the KP1019 induced cytotoxicity in two different strains, and this showed no cytotoxicity for 4T1, while cisplatin was more cytotoxic to this strain (over 12.5 uM doses). In contrast, KP1019 was more cytotoxic to NIH-3T3 at doses from 25 uM. In the 72-hour period, both complexes were cytotoxic similar in both cell lines from 12.5 uM doses. Additionally, the cytotoxic effect of cisplatin were KP1019 and different in lineage 4T1 (doses 1.25 and 2.5 uM). Furthermore, the morphology of 4T1 cells was examined under an optical microscope after treatment for 24 hours with 20 uM of KP1019 or cisplatin (IC50) and observed several changes related to cytotoxicity and rounding of the cells and increasing the amount of cytoplasmic vesicles. Thus, it is suggested that the cytotoxic effect of KP1019 was dose-dependent cell line and evaluated time and this cytotoxicity is associated with morphologic changes from cell death process, which enhances the excellent potential KP1019 for use in cancer chemotherapy breast cancer.
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Wedding, Jason Lee. "Application of Synchrotron-Based Spectroscopic Techniques XAS and XFM Towards Probing the Cellular Metallome." Thesis, 2019. http://hdl.handle.net/2440/120496.

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The use of synchrotron-based experimental techniques has gained increasing recognition, as they are powerful tools to explore the cellular metallome. Metallomics, which encompasses all aspects of biological systems, especially the cell, involved in metal speciation and metabolism; and probes the spatial metal ion distributions within differing cell types, organelles and regulating proteins. As such, the precise imaging of metal ion and intracellular organelle distribution within the wider context of cellular regulation pathways and biological function is essential. Biological systems are inherently complex, with the metal of interest being contained within an intricate biological matrix. Synchrotron-based techniques have benefits that laboratory-based fluorescence experiments do not; reduced required sample preparation, direct metal distribution imaging, and the ability to characterise the chemical nature of the intracellular metal pool. This thesis describes the use of two synchrotron-based techniques; X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM), to investigate the effects of biometal-based agents on the intracellular metallome. Firstly, the intracellular fate of a luminescent rhenium(I) tricarbonyl tetrazolato complex probe within 22Rv1 human prostate epithelial carcinoma cells was explored. It was demonstrated that the cellular distribution of the luminescent imaging agent could be determined by monitoring the luminescence from the compound using optical microscopy and then correlated with the cellular distributions of rhenium and iodine contained in the species within the same samples as measured using microprobe XFM. A combination of XAS and XFM was employed to investigate the neuroprotective action purported for diphenyl diselenide. This was achieved by treating SH-SY5Y human neurocarcinoma epithelial cells with more water soluble diphenyl diselenide analogues; bis(2-aminodiphenyl)diselenide and bis(2-nitrodiphenyl)diselenide. These two studies showcased that the advantageous, simultaneous collection of metallome and mode of action information can provide a pathway to exploring neurological diseases and disorders, the production of better therapeutic agents, and could be used diagnostically in medicine. Finally, the anticancer action of NKP-1339, a KP1019 analogue, within A549 human lung adenocarcinoma epithelial cells was investigated. Initially a co-localisation of NKP-1339, or its ruthenium-containing metabolites, with intracellular iron and copper was observed. Subsequent attempts to visualise a mitochondrial compartmentalisation of the NKP-1339 or its ruthenium-based metabolites utilising a combination of optical and synchrotron-based fluorescence microscopy were unsuccessful. The studies into the Re-I probe and diphenyl diselenide analogues showcased the power of synchrotron-based spectroscopic techniques yielding mode-of-action information as well as visualising the effects of the biometal-containing agents on the intracellular metallome. The study into NKP-1339, while largely unsuccessful, did provide similar information related to the perturbation of the intracellular metallome while not yielding mode-of-action information.
Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2019
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Книги з теми "KP1019"

1

Directory of European Agricultural Organizations/Kp109. Unipub, 1985.

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2

Directory of European Agricultural Organizations/Kp109. Unipub, 1985.

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3

Improving Venture Capital Opportunities in Europe/Kp108. Kogan Page Ltd, 1985.

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4

Lovasz, J. Incentives for Industrial Research, Development and Innovation/Kp107. Kogan Page Ltd, 1986.

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5

Micad '85: Proceedings of the 4th European Conference on Cad/Cam and Computer Graphics/Kp105. Unipub, 1985.

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Частини книг з теми "KP1019"

1

"5. THE DECEPTIVELY SIMILAR RUTHENIUM(III) DRUG CANDIDATES KP1019 AND NAMI-A HAVE DIFFERENT ACTIONS. WHAT DID WE LEARN IN THE PAST 30 YEARS?" In Metallo-Drugs: Development and Action of Anticancer Agents, 141–70. De Gruyter, 2018. http://dx.doi.org/10.1515/9783110470734-005.

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Тези доповідей конференцій з теми "KP1019"

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Lukianova, Anna A., Peter V. Evseev, Mikhail M. Shneider, Ekaterina A. Gornostal, Yulia Mikhaylova, Andrey Shelenkov, and Konstantin A. Miroshnikov. "Pre-Treatment With Polysaccharide Depolymerase Enhances the Infective Performance of Klebsiella Phage KP1079." In 2022 Ural-Siberian Conference on Computational Technologies in Cognitive Science, Genomics and Biomedicine (CSGB). IEEE, 2022. http://dx.doi.org/10.1109/csgb56354.2022.9865515.

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2

Alte, Beatrix, Christine Pirker, Thomas Mohr, Kushtrim Kryeziu, Bernhard K. Keppler, Petra Heffeter, and Walter Berger. "Abstract 2573: Investigation of factors involved in the hypersensitivity to KP1339-treatment." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2573.

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3

Baier, Dina Salome, Beatrix Schoenhacker-Alte, Christine Pirker, Bernhard Englinger, Thomas Mohr, Samuel Meier-Menches, Clemens Roehrl, et al. "Abstract 1839: Lipid metabolism as target and modulator of KP1339 anticancer activity." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-1839.

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Heffeter, Petra, Bihter Atil, Ute Jungwirth, Wilfried Koerner, Michael Micksche, Bernhard K. Keppler, and Walter Berger. "Abstract C103:In vitroandin vivoanticancer activity of the new ruthenium compound KP1339 against human liver cancer models." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-c103.

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Heffeter, Petra, Bihter Atil, Kushtrim Kryeziu, Ute Jungwirth, Elisabeth Gal, Bernhard K. Keppler, and Walter Berger. "Abstract 3541: Combination of the ruthenium compound KP1339 with the tyrosine kinase inhibitor sorafenib: A promising approach for the treatment of human hepatoma." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3541.

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Звіти організацій з теми "KP1019"

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Smith, S. L., L. P. Roy, A. G. Lewkowicz, and J. Chartrand. Ground thermal data collection along the Alaska Highway corridor (KP1559-1895), Yukon, summer 2016. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2017. http://dx.doi.org/10.4095/306304.

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Smith, S. L., M. Ednie, and J. Chartrand. Ground thermal data collection along the Alaska Highway corridor (KP1559-1895), Yukon, summer 2015. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2016. http://dx.doi.org/10.4095/298769.

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