LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Zurück zur letzten Suche Suchhistorie
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Amrutha Nisthul, A"
  2. AU="Fischer, K." AU="Fischer, K."
  3. AU="Pushap Raj"
  4. AU="Martin-Vila, Alicia"
  5. AU="Houska, Jiri"
  6. AU="Uwer, Lionel"
  7. AU="Yoo, Heejin"

Suchergebnis

Treffer 1 - 4 von insgesamt 4

Suchoptionen

  1. Artikel ; Online: Virtual screening-based identification of novel fatty acid synthase inhibitor and evaluation of its antiproliferative activity in breast cancer cells.

    Amrutha Nisthul, A / Archana, P R / Anto, Ruby John / Sadasivan, C

    Journal of molecular graphics & modelling

    2021  Band 105, Seite(n) 107903

    Abstract: Cancer cells activate de novo lipogenesis by overexpressing the lipogenic enzymes ACLY, ACC and FASN to support rapid cell division. FASN, previously known as oncogenic antigen-519 (OA-519) catalyzes seven sequential reactions to synthesize palmitic acid ...

    Abstract Cancer cells activate de novo lipogenesis by overexpressing the lipogenic enzymes ACLY, ACC and FASN to support rapid cell division. FASN, previously known as oncogenic antigen-519 (OA-519) catalyzes seven sequential reactions to synthesize palmitic acid (C16) from substrates acetyl CoA, and malonyl CoA. The dependence of cancer cells on FASN-derived lipids and the differential expression of FASN in cancer cells compared to their normal counterparts make it an attractive metabolic drug target in cancer therapy. In the present study, an attempt has been made to identify potent FASN inhibitors from Asinex-Synergy compound database using structure-based virtual screening. The serial docking protocols of increasing precisions identified LEG-17649942, with glide score -10.34 kcal/mol as a promising compound which can directly interact with active site residues H293 and H331. LEG-17649942 possesses drug-like pharmacokinetic properties as predicted by Qikprop. LEG-17649942 exhibited cytotoxicity in breast cancer cell lines SK-BR-3, MCF-7 and MDA-MB-231 with maximum activity against MDA-MB-231 cells with IC50 of 50 μM. The study put forward LEG-17649942 as a novel drug-lead compound against triple negative breast cancer with an exquisite binding pattern to FASN-KS domain.
    Mesh-Begriff(e) Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Fatty Acid Synthases/antagonists & inhibitors ; Female ; Humans
    Chemische Substanzen Fatty Acid Synthases (EC 2.3.1.85)
    Sprache Englisch
    Erscheinungsdatum 2021-03-20
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1396450-1
    ISSN 1873-4243 ; 1093-3263
    ISSN (online) 1873-4243
    ISSN 1093-3263
    DOI 10.1016/j.jmgm.2021.107903
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 3491: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  2. Artikel ; Online: Pyridine derivatives as anticancer lead compounds with Fatty Acid Synthase as the target: An in silico-guided in vitro study.

    Amrutha, Nisthul A / Archana, P Retnakumari / Mohan, Shankar G / Anto, Ruby John / Sadasivan, C

    Journal of cellular biochemistry

    2019  Band 120, Heft 10, Seite(n) 16643–16657

    Abstract: For the past few decades, structure-based drug discovery (SBDD) has become an inevitable technique in the drug development process for screening hit compounds against therapeutic targets. Here, we have successfully used the SBDD approach viz. virtual ... ...

    Abstract For the past few decades, structure-based drug discovery (SBDD) has become an inevitable technique in the drug development process for screening hit compounds against therapeutic targets. Here, we have successfully used the SBDD approach viz. virtual high-throughput screening to identify potential inhibitors against the Ketoacyl synthase (KS) domain of Fatty acid synthase (FASN). Overexpression of FASN, and subsequent enhancement of de novo lipogenesis is a key survival strategy of cancer cells. Hence, targeting lipid metabolism using FASN inhibitors has been considered as a promising method to induce metabolic stress, thereby posing a survival disadvantage to cancer cells. In the present study, we have successfully identified eight FASN inhibitors from Asinex Elite database by implementing in silico tools. Five of the hit compounds share a common ring structure, which enables characteristic binding interactions with FASN-KS. Among them, in vitro validation showed that SFA 22637550 possesses significant FASN inhibitory activity and antiproliferative effect in human cancer cells of various origins. The maximum sensitivity was exhibited towards HepG2 hepatocellular carcinoma cells (IC50 = 28 µM). The mode of cell death was found to be apoptosis with a significant increase in SubG0 population without affecting any other phases of the cell cycle. The current study puts forward an excellent core structure for the development of potent FASN inhibitors for successfully targeting cancer cell metabolism, thereby causing selective cell death.
    Mesh-Begriff(e) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Cycle/drug effects ; Computer Simulation ; Drug Screening Assays, Antitumor ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Fatty Acid Synthase, Type I/antagonists & inhibitors ; Fatty Acid Synthase, Type I/chemistry ; Fatty Acid Synthase, Type I/metabolism ; Hep G2 Cells ; Humans ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/metabolism ; Pyridines/chemistry ; Pyridines/pharmacology
    Chemische Substanzen Antineoplastic Agents ; Enzyme Inhibitors ; Neoplasm Proteins ; Pyridines ; FASN protein, human (EC 2.3.1.85) ; Fatty Acid Synthase, Type I (EC 2.3.1.85)
    Sprache Englisch
    Erscheinungsdatum 2019-05-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 392402-6
    ISSN 1097-4644 ; 0730-2312
    ISSN (online) 1097-4644
    ISSN 0730-2312
    DOI 10.1002/jcb.28923
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 1114: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  3. Artikel: Pharmacological attenuation of melanoma by tryptanthrin pertains to the suppression of MITF-M through MEK/ERK signaling axis

    Shabna, Anwar / Antony, Jayesh / Vijayakurup, Vinod / Saikia, Minakshi / Liju, Vijayasteltar B. / Retnakumari, Archana P. / Amrutha, Nisthul A. / Alex, Vijai V. / Swetha, Mundanattu / Aiswarya, Sreekumar U. / Jannet, Somaraj / Unni, Uma Subramanian / Sundaram, Sankar / Sherin, Daisy R. / Anto, Nikhil Ponnoor / Bava, Smitha V. / Chittalakkottu, Sadasivan / Ran, Sophia / Anto, Ruby John

    Cellular and molecular life sciences. 2022 Sept., v. 79, no. 9

    2022  

    Abstract: Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize BRAFⱽ⁶⁰⁰ᴱ, as a focal point for targeted therapy. However, therapy resistance developed in melanoma patients against the conventional anti- ... ...

    Abstract Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize BRAFⱽ⁶⁰⁰ᴱ, as a focal point for targeted therapy. However, therapy resistance developed in melanoma patients against the conventional anti-melanoma drugs hinders the ultimate benefits of targeted therapies. A major mechanism by which melanoma cells attain therapy resistance is via the activation of microphthalmia-associated transcription factor-M (MITF-M), the key transcription factor and oncogene aiding the survival of melanoma cells. We demonstrate that tryptanthrin (Tpn), an indole quinazoline alkaloid, which we isolated and characterized from Wrightia tinctoria, exhibits remarkable anti-tumor activity towards human melanoma through the down-regulation of MITF-M. Microarray analysis of Tpn-treated melanoma cells followed by a STRING protein association network analysis revealed that differential expression of genes in melanoma converges at MITF-M. Furthermore, in vitro and in vivo studies conducted using melanoma cells with differential MITF-M expression status, endogenously or ectopically, demonstrated that the anti-melanoma activity of Tpn is decisively contingent on its efficacy in down-regulating MITF-M expression. Tpn potentiates the degradation of MITF-M via the modulation of MEK1/2-ERK1/2-MITF-M signaling cascades. Murine models demonstrate the efficacy of Tpn in attenuating the migration and metastasis of melanoma cells, while remaining pharmacologically safe. In addition, Tpn suppresses the expression of mutated BRAFⱽ⁶⁰⁰ᴱ and inhibits Casein Kinase 2α, a pro-survival enzyme that regulates ERK1/2 homeostasis in many tumor types, including melanoma. Together, we point to a promising anti-melanoma drug in Tpn, by virtue of its attributes to impede melanoma invasion and metastasis by attenuating MITF-M.
    Schlagwörter Wrightia tinctoria ; alkaloids ; antineoplastic activity ; drugs ; gene expression regulation ; homeostasis ; humans ; indoles ; melanoma ; metastasis ; mice ; microarray technology ; non-specific serine/threonine protein kinase ; oncogenes ; therapeutics ; transcription factors
    Sprache Englisch
    Erscheinungsverlauf 2022-09
    Umfang p. 478.
    Erscheinungsort Springer International Publishing
    Dokumenttyp Artikel
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04476-y
    Datenquelle NAL Katalog (AGRICOLA)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Bonn

    Z 4' 47/14: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  4. Artikel ; Online: Pharmacological attenuation of melanoma by tryptanthrin pertains to the suppression of MITF-M through MEK/ERK signaling axis.

    Shabna, Anwar / Antony, Jayesh / Vijayakurup, Vinod / Saikia, Minakshi / Liju, Vijayasteltar B / Retnakumari, Archana P / Amrutha, Nisthul A / Alex, Vijai V / Swetha, Mundanattu / Aiswarya, Sreekumar U / Jannet, Somaraj / Unni, Uma Subramanian / Sundaram, Sankar / Sherin, Daisy R / Anto, Nikhil Ponnoor / Bava, Smitha V / Chittalakkottu, Sadasivan / Ran, Sophia / Anto, Ruby John

    Cellular and molecular life sciences : CMLS

    2022  Band 79, Heft 9, Seite(n) 478

    Abstract: Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize ... ...

    Abstract Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize BRAF
    Mesh-Begriff(e) Animals ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; Melanoma/genetics ; Mice ; Microphthalmia-Associated Transcription Factor/genetics ; Microphthalmia-Associated Transcription Factor/metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/metabolism ; Quinazolines
    Chemische Substanzen MITF protein, human ; Microphthalmia-Associated Transcription Factor ; Quinazolines ; tryptanthrine (13220-57-0) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
    Sprache Englisch
    Erscheinungsdatum 2022-08-10
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04476-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 195: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

Zum Seitenanfang