Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein
Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79...
Gespeichert in:
| Veröffentlicht in: | Molecules (Basel, Switzerland) Switzerland), 2021-08, Vol.26 (17), p.5300 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 17 |
| container_start_page | 5300 |
| container_title | Molecules (Basel, Switzerland) |
| container_volume | 26 |
| creator | Bon, Corentin Si, Yang Pernak, Melanie Barbachowska, Magdalena Levi-Acobas, Eva Cadet Daniel, Veronique Jallet, Corinne Ruzic, Dusan Djokovic, Nemanja Djikić, Teodora Nikolic, Katarina Halby, Ludovic Arimondo, Paola B |
| description | Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect. |
| doi_str_mv | 10.3390/molecules26175300 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_fd33e24dcc5344ff89fd40d4ff9a2be1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_fd33e24dcc5344ff89fd40d4ff9a2be1</doaj_id><sourcerecordid>2571436975</sourcerecordid><originalsourceid>FETCH-LOGICAL-c531t-a00290e2c6a62355aaed3502aa2f6cdddcc33eee11948121baff996ce3fe5bd43</originalsourceid><addsrcrecordid>eNplkk1vEzEQhlcIREvgB3BBlrhwCfhrN_EFKYSPRlpUJMLZmtjjxGGzDrY3Uv49TlOqtpw88rzzzIfeqnrN6HshFP2wCx2aocPEGzapBaVPqksmOR0LKtXTe_FF9SKlLaWcSVY_ry6ErCmdCHFZbX4e-7zB5BOB3pJPPnRh7Q10ZGayP_h8JMERIPNjDilD9oYs-o1f-RziKfO9bSNpcfiNOw9kCXGN2fdrUpjk8_WSteRHDBl9_7J65qBL-Or2HVW_vn5Zzq_G7fW3xXzWjk0tWB5DGVJR5KaBhou6BkArasoBuGuMtdYYIRCRMSWnjLMVOKdUY1A4rFdWilG1OHNtgK3eR7-DeNQBvL75CHGtIZY1OtTOFhSXBVkLKZ2bKmcltSVSwFfICuvjmbUfVju0BvscoXsAfZjp_Uavw0FPpZCMqgIYnwGbR2VXs1bvIWUcoqZFy6aT5nBq-O62YQx_BkxZ73wy2HXQYxiS5vWEKc6UOqHfPpJuwxD7ctoblRSNKpYYVeysMjGkFNHdTcGoPnlI_-ehUvPm_tZ3Ff9MI_4CCi3FwQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2571436975</pqid></control><display><type>article</type><title>Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Bon, Corentin ; Si, Yang ; Pernak, Melanie ; Barbachowska, Magdalena ; Levi-Acobas, Eva ; Cadet Daniel, Veronique ; Jallet, Corinne ; Ruzic, Dusan ; Djokovic, Nemanja ; Djikić, Teodora ; Nikolic, Katarina ; Halby, Ludovic ; Arimondo, Paola B</creator><creatorcontrib>Bon, Corentin ; Si, Yang ; Pernak, Melanie ; Barbachowska, Magdalena ; Levi-Acobas, Eva ; Cadet Daniel, Veronique ; Jallet, Corinne ; Ruzic, Dusan ; Djokovic, Nemanja ; Djikić, Teodora ; Nikolic, Katarina ; Halby, Ludovic ; Arimondo, Paola B</creatorcontrib><description>Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules26175300</identifier><identifier>PMID: 34500733</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenosine ; Alcohol ; Biological activity ; bisubstrates ; Cancer ; Carbon ; Cell proliferation ; Clinical trials ; Crystal structure ; Cytostatic Agents - therapeutic use ; DOT1L ; Enzymatic activity ; Epigenetics ; Gene expression ; histone methylation ; Histone methyltransferase ; Histone-Lysine N-Methyltransferase - metabolism ; Histones ; Histones - metabolism ; HMT inhibitors ; Humans ; Leukemia ; Leukemia - drug therapy ; Leukemia - metabolism ; Life Sciences ; Lysine ; Metabolism ; Methylation ; Methylation - drug effects ; MLL rearranged leukemia ; Molecular Structure ; Proteins ; rational drug design</subject><ispartof>Molecules (Basel, Switzerland), 2021-08, Vol.26 (17), p.5300</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-a00290e2c6a62355aaed3502aa2f6cdddcc33eee11948121baff996ce3fe5bd43</citedby><cites>FETCH-LOGICAL-c531t-a00290e2c6a62355aaed3502aa2f6cdddcc33eee11948121baff996ce3fe5bd43</cites><orcidid>0000-0002-0546-8265 ; 0000-0002-6198-239X ; 0000-0002-6577-7465 ; 0000-0001-5175-4396 ; 0000-0001-9972-3492 ; 0000-0002-4590-6522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434109/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434109/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34500733$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-03411876$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bon, Corentin</creatorcontrib><creatorcontrib>Si, Yang</creatorcontrib><creatorcontrib>Pernak, Melanie</creatorcontrib><creatorcontrib>Barbachowska, Magdalena</creatorcontrib><creatorcontrib>Levi-Acobas, Eva</creatorcontrib><creatorcontrib>Cadet Daniel, Veronique</creatorcontrib><creatorcontrib>Jallet, Corinne</creatorcontrib><creatorcontrib>Ruzic, Dusan</creatorcontrib><creatorcontrib>Djokovic, Nemanja</creatorcontrib><creatorcontrib>Djikić, Teodora</creatorcontrib><creatorcontrib>Nikolic, Katarina</creatorcontrib><creatorcontrib>Halby, Ludovic</creatorcontrib><creatorcontrib>Arimondo, Paola B</creatorcontrib><title>Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.</description><subject>Adenosine</subject><subject>Alcohol</subject><subject>Biological activity</subject><subject>bisubstrates</subject><subject>Cancer</subject><subject>Carbon</subject><subject>Cell proliferation</subject><subject>Clinical trials</subject><subject>Crystal structure</subject><subject>Cytostatic Agents - therapeutic use</subject><subject>DOT1L</subject><subject>Enzymatic activity</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>histone methylation</subject><subject>Histone methyltransferase</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Histones</subject><subject>Histones - metabolism</subject><subject>HMT inhibitors</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia - drug therapy</subject><subject>Leukemia - metabolism</subject><subject>Life Sciences</subject><subject>Lysine</subject><subject>Metabolism</subject><subject>Methylation</subject><subject>Methylation - drug effects</subject><subject>MLL rearranged leukemia</subject><subject>Molecular Structure</subject><subject>Proteins</subject><subject>rational drug design</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNplkk1vEzEQhlcIREvgB3BBlrhwCfhrN_EFKYSPRlpUJMLZmtjjxGGzDrY3Uv49TlOqtpw88rzzzIfeqnrN6HshFP2wCx2aocPEGzapBaVPqksmOR0LKtXTe_FF9SKlLaWcSVY_ry6ErCmdCHFZbX4e-7zB5BOB3pJPPnRh7Q10ZGayP_h8JMERIPNjDilD9oYs-o1f-RziKfO9bSNpcfiNOw9kCXGN2fdrUpjk8_WSteRHDBl9_7J65qBL-Or2HVW_vn5Zzq_G7fW3xXzWjk0tWB5DGVJR5KaBhou6BkArasoBuGuMtdYYIRCRMSWnjLMVOKdUY1A4rFdWilG1OHNtgK3eR7-DeNQBvL75CHGtIZY1OtTOFhSXBVkLKZ2bKmcltSVSwFfICuvjmbUfVju0BvscoXsAfZjp_Uavw0FPpZCMqgIYnwGbR2VXs1bvIWUcoqZFy6aT5nBq-O62YQx_BkxZ73wy2HXQYxiS5vWEKc6UOqHfPpJuwxD7ctoblRSNKpYYVeysMjGkFNHdTcGoPnlI_-ehUvPm_tZ3Ff9MI_4CCi3FwQ</recordid><startdate>20210831</startdate><enddate>20210831</enddate><creator>Bon, Corentin</creator><creator>Si, Yang</creator><creator>Pernak, Melanie</creator><creator>Barbachowska, Magdalena</creator><creator>Levi-Acobas, Eva</creator><creator>Cadet Daniel, Veronique</creator><creator>Jallet, Corinne</creator><creator>Ruzic, Dusan</creator><creator>Djokovic, Nemanja</creator><creator>Djikić, Teodora</creator><creator>Nikolic, Katarina</creator><creator>Halby, Ludovic</creator><creator>Arimondo, Paola B</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0546-8265</orcidid><orcidid>https://orcid.org/0000-0002-6198-239X</orcidid><orcidid>https://orcid.org/0000-0002-6577-7465</orcidid><orcidid>https://orcid.org/0000-0001-5175-4396</orcidid><orcidid>https://orcid.org/0000-0001-9972-3492</orcidid><orcidid>https://orcid.org/0000-0002-4590-6522</orcidid></search><sort><creationdate>20210831</creationdate><title>Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein</title><author>Bon, Corentin ; Si, Yang ; Pernak, Melanie ; Barbachowska, Magdalena ; Levi-Acobas, Eva ; Cadet Daniel, Veronique ; Jallet, Corinne ; Ruzic, Dusan ; Djokovic, Nemanja ; Djikić, Teodora ; Nikolic, Katarina ; Halby, Ludovic ; Arimondo, Paola B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c531t-a00290e2c6a62355aaed3502aa2f6cdddcc33eee11948121baff996ce3fe5bd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine</topic><topic>Alcohol</topic><topic>Biological activity</topic><topic>bisubstrates</topic><topic>Cancer</topic><topic>Carbon</topic><topic>Cell proliferation</topic><topic>Clinical trials</topic><topic>Crystal structure</topic><topic>Cytostatic Agents - therapeutic use</topic><topic>DOT1L</topic><topic>Enzymatic activity</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>histone methylation</topic><topic>Histone methyltransferase</topic><topic>Histone-Lysine N-Methyltransferase - metabolism</topic><topic>Histones</topic><topic>Histones - metabolism</topic><topic>HMT inhibitors</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia - drug therapy</topic><topic>Leukemia - metabolism</topic><topic>Life Sciences</topic><topic>Lysine</topic><topic>Metabolism</topic><topic>Methylation</topic><topic>Methylation - drug effects</topic><topic>MLL rearranged leukemia</topic><topic>Molecular Structure</topic><topic>Proteins</topic><topic>rational drug design</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bon, Corentin</creatorcontrib><creatorcontrib>Si, Yang</creatorcontrib><creatorcontrib>Pernak, Melanie</creatorcontrib><creatorcontrib>Barbachowska, Magdalena</creatorcontrib><creatorcontrib>Levi-Acobas, Eva</creatorcontrib><creatorcontrib>Cadet Daniel, Veronique</creatorcontrib><creatorcontrib>Jallet, Corinne</creatorcontrib><creatorcontrib>Ruzic, Dusan</creatorcontrib><creatorcontrib>Djokovic, Nemanja</creatorcontrib><creatorcontrib>Djikić, Teodora</creatorcontrib><creatorcontrib>Nikolic, Katarina</creatorcontrib><creatorcontrib>Halby, Ludovic</creatorcontrib><creatorcontrib>Arimondo, Paola B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bon, Corentin</au><au>Si, Yang</au><au>Pernak, Melanie</au><au>Barbachowska, Magdalena</au><au>Levi-Acobas, Eva</au><au>Cadet Daniel, Veronique</au><au>Jallet, Corinne</au><au>Ruzic, Dusan</au><au>Djokovic, Nemanja</au><au>Djikić, Teodora</au><au>Nikolic, Katarina</au><au>Halby, Ludovic</au><au>Arimondo, Paola B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2021-08-31</date><risdate>2021</risdate><volume>26</volume><issue>17</issue><spage>5300</spage><pages>5300-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34500733</pmid><doi>10.3390/molecules26175300</doi><orcidid>https://orcid.org/0000-0002-0546-8265</orcidid><orcidid>https://orcid.org/0000-0002-6198-239X</orcidid><orcidid>https://orcid.org/0000-0002-6577-7465</orcidid><orcidid>https://orcid.org/0000-0001-5175-4396</orcidid><orcidid>https://orcid.org/0000-0001-9972-3492</orcidid><orcidid>https://orcid.org/0000-0002-4590-6522</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1420-3049 |
| ispartof | Molecules (Basel, Switzerland), 2021-08, Vol.26 (17), p.5300 |
| issn | 1420-3049 1420-3049 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_fd33e24dcc5344ff89fd40d4ff9a2be1 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenosine Alcohol Biological activity bisubstrates Cancer Carbon Cell proliferation Clinical trials Crystal structure Cytostatic Agents - therapeutic use DOT1L Enzymatic activity Epigenetics Gene expression histone methylation Histone methyltransferase Histone-Lysine N-Methyltransferase - metabolism Histones Histones - metabolism HMT inhibitors Humans Leukemia Leukemia - drug therapy Leukemia - metabolism Life Sciences Lysine Metabolism Methylation Methylation - drug effects MLL rearranged leukemia Molecular Structure Proteins rational drug design |
| title | Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T07%3A11%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis%20and%20Biological%20Activity%20of%20a%20Cytostatic%20Inhibitor%20of%20MLLr%20Leukemia%20Targeting%20the%20DOT1L%20Protein&rft.jtitle=Molecules%20(Basel,%20Switzerland)&rft.au=Bon,%20Corentin&rft.date=2021-08-31&rft.volume=26&rft.issue=17&rft.spage=5300&rft.pages=5300-&rft.issn=1420-3049&rft.eissn=1420-3049&rft_id=info:doi/10.3390/molecules26175300&rft_dat=%3Cproquest_doaj_%3E2571436975%3C/proquest_doaj_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2571436975&rft_id=info:pmid/34500733&rft_doaj_id=oai_doaj_org_article_fd33e24dcc5344ff89fd40d4ff9a2be1&rfr_iscdi=true |