FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2805664394> ?p ?o ?g. }

• W2805664394 endingPage "26369" @default.
• W2805664394 startingPage "26353" @default.
• W2805664394 abstract "// Joachim R. Göthert 1 , Roze Imsak 1 , Michael Möllmann 1 , Stefanie Kesper 1 , Maria Göbel 1 , Ulrich Dührsen 1 , Arne Scholz 2 , Ulrich Lücking 2 , Matthias Baumann 3 , Anke Unger 3 , Carsten Schultz-Fademrecht 3 , Bert Klebl 3 , Jan Eickhoff 3 , Axel Choidas 3 and Jan Dürig 1 1 Department of Hematology, West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany 2 Bayer AG, Pharmaceuticals, Drug Discovery, Berlin, Germany 3 Lead Discovery Center GmbH (LDC), Dortmund, Germany Correspondence to: Joachim R. Göthert, email: joachim.goethert@uk-essen.de Keywords: chronic lymphocytic leukemia; cyclin-dependent kinase 9; MEC-1 cell line; TCL1 transgenic mice; NSG mice Received: August 16, 2017      Accepted: April 07, 2018      Published: May 29, 2018 ABSTRACT Onset of progression even during therapy with novel drugs remains an issue in chronic lymphocytic leukemia (CLL). Thus, there is ongoing demand for novel agents. Approaches targeting cyclin-dependent kinases (CDK) have reached the clinical trial stage. CDK9 mediating RNA transcriptional elongation is the evolving pivotal CLL CDK inhibitor target. However, more CDK9 selective compounds are desirable. Here, we describe the CDK9 inhibitor LDC526 displaying a low nanomolar biochemical activity against CDK9 and an at least 50-fold selectivity against other CDKs. After demonstrating in vitro MEC-1 cell line and primary human CLL cell cytotoxicity we evaluated the LDC526 in vivo effect on human CLL cells transplanted into NOD/scid/γc null (NSG) mice. LDC526 administration (75 mg/kg) for 5 days resulted in a 77% reduction of human CLL cells in NSG spleens compared to carrier control treatment. Next, we longitudinally studied the LDC526 impact on circulating CLL cells in the TCL1 transgenic mouse model. LDC526 (50 mg/kg) administration for two days led to a 16-fold reduction of blood CLL cell numbers. Remarkably, residual CLL cells exhibited significantly increased intracellular BCL-2 levels. However, the LDC526 cytotoxic effect was not restricted to CLL cells as also declining numbers of normal B and T lymphocytes were observed in LDC526 treated TCL1 mice. Taken together, our in vivo data provide a strong rational for continued LDC526 development in CLL therapy and argue for the combination with BCL-2 inhibitors." @default.
• W2805664394 created "2018-06-13" @default.
• W2805664394 creator A5002804657 @default.
• W2805664394 creator A5005029408 @default.
• W2805664394 creator A5009093201 @default.
• W2805664394 creator A5024223640 @default.
• W2805664394 creator A5030057178 @default.
• W2805664394 creator A5044963199 @default.
• W2805664394 creator A5046537550 @default.
• W2805664394 creator A5052263137 @default.
• W2805664394 creator A5074571641 @default.
• W2805664394 creator A5077558723 @default.
• W2805664394 creator A5083112108 @default.
• W2805664394 creator A5085255418 @default.
• W2805664394 creator A5086564468 @default.
• W2805664394 creator A5089320427 @default.
• W2805664394 creator A5090413812 @default.
• W2805664394 date "2018-05-29" @default.
• W2805664394 modified "2023-09-25" @default.
• W2805664394 title "Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia" @default.
• W2805664394 cites W1510649334 @default.
• W2805664394 cites W1537838684 @default.
• W2805664394 cites W1549691519 @default.
• W2805664394 cites W1611726375 @default.
• W2805664394 cites W1976767301 @default.
• W2805664394 cites W1981113072 @default.
• W2805664394 cites W1981472067 @default.
• W2805664394 cites W1983384475 @default.
• W2805664394 cites W1984072004 @default.
• W2805664394 cites W1984999956 @default.
• W2805664394 cites W1987880662 @default.
• W2805664394 cites W2006528910 @default.
• W2805664394 cites W2006950258 @default.
• W2805664394 cites W2007930689 @default.
• W2805664394 cites W2009593167 @default.
• W2805664394 cites W2017898416 @default.
• W2805664394 cites W2018466312 @default.
• W2805664394 cites W2028703351 @default.
• W2805664394 cites W2037198742 @default.
• W2805664394 cites W2040117983 @default.
• W2805664394 cites W2045378539 @default.
• W2805664394 cites W2047115666 @default.
• W2805664394 cites W2049090395 @default.
• W2805664394 cites W2055091448 @default.
• W2805664394 cites W2066107979 @default.
• W2805664394 cites W2066404900 @default.
• W2805664394 cites W2069326426 @default.
• W2805664394 cites W2079721992 @default.
• W2805664394 cites W2080797004 @default.
• W2805664394 cites W2081379689 @default.
• W2805664394 cites W2083470652 @default.
• W2805664394 cites W2088260828 @default.
• W2805664394 cites W2093538016 @default.
• W2805664394 cites W2103580937 @default.
• W2805664394 cites W2121396722 @default.
• W2805664394 cites W2123045903 @default.
• W2805664394 cites W2132276725 @default.
• W2805664394 cites W2138586972 @default.
• W2805664394 cites W2140642045 @default.
• W2805664394 cites W2150439521 @default.
• W2805664394 cites W2156261378 @default.
• W2805664394 cites W2158108546 @default.
• W2805664394 cites W2161817637 @default.
• W2805664394 cites W2167292349 @default.
• W2805664394 cites W2171651374 @default.
• W2805664394 cites W2172242534 @default.
• W2805664394 cites W2176912713 @default.
• W2805664394 cites W2291659253 @default.
• W2805664394 cites W2295348655 @default.
• W2805664394 cites W2301131921 @default.
• W2805664394 cites W2336830482 @default.
• W2805664394 cites W2490617194 @default.
• W2805664394 cites W2515842163 @default.
• W2805664394 cites W2521204548 @default.
• W2805664394 cites W2558640761 @default.
• W2805664394 cites W2559419065 @default.
• W2805664394 cites W2580602149 @default.
• W2805664394 cites W2587371140 @default.
• W2805664394 cites W2588126420 @default.
• W2805664394 cites W2705287825 @default.
• W2805664394 cites W4232115491 @default.
• W2805664394 cites W4250894669 @default.
• W2805664394 doi "https://doi.org/10.18632/oncotarget.25293" @default.
• W2805664394 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5995184" @default.
• W2805664394 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29899864" @default.
• W2805664394 hasPublicationYear "2018" @default.
• W2805664394 type Work @default.
• W2805664394 sameAs 2805664394 @default.
• W2805664394 citedByCount "5" @default.
• W2805664394 countsByYear W28056643942020 @default.
• W2805664394 countsByYear W28056643942021 @default.
• W2805664394 crossrefType "journal-article" @default.
• W2805664394 hasAuthorship W2805664394A5002804657 @default.
• W2805664394 hasAuthorship W2805664394A5005029408 @default.
• W2805664394 hasAuthorship W2805664394A5009093201 @default.
• W2805664394 hasAuthorship W2805664394A5024223640 @default.
• W2805664394 hasAuthorship W2805664394A5030057178 @default.
• W2805664394 hasAuthorship W2805664394A5044963199 @default.

• next