Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of MYC transcription and activity. However,...
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| Veröffentlicht in: | Leukemia 2017-08, Vol.31 (8), p.1760-1769 |
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| creator | Siu, K T Ramachandran, J Yee, A J Eda, H Santo, L Panaroni, C Mertz, J A Sims III, R J Cooper, M R Raje, N |
| description | Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of
MYC
transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G
1
cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the
in vivo
efficacy of CPI-0610 in a MM xenograft mouse model. Our study found
IKZF1
and
IRF4
to be among the primary targets of CPI-0610, along with
MYC
. Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show
in vitro
synergism, in part due to concomitant suppression of
IKZF1
,
IRF4
and
MYC
, providing a rationale for clinical testing of this drug combination in MM patients. |
| doi_str_mv | 10.1038/leu.2016.355 |
| format | Article |
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MYC
transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G
1
cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the
in vivo
efficacy of CPI-0610 in a MM xenograft mouse model. Our study found
IKZF1
and
IRF4
to be among the primary targets of CPI-0610, along with
MYC
. Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show
in vitro
synergism, in part due to concomitant suppression of
IKZF1
,
IRF4
and
MYC
, providing a rationale for clinical testing of this drug combination in MM patients.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2016.355</identifier><identifier>PMID: 27890933</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 38/39 ; 38/77 ; 38/89 ; 45/22 ; 631/67/1059/153 ; 631/67/1990/804 ; 631/92/436/108 ; 64/60 ; 692/308/2778 ; 692/700/565/1436/1437 ; 96/106 ; 96/109 ; Animals ; Anticancer properties ; Antimitotic agents ; Antineoplastic agents ; Antitumor activity ; Apoptosis ; Benzazepines - pharmacology ; Binding proteins ; Biocompatibility ; Biotechnology ; Bone marrow ; Cancer Research ; Caspase ; Cell cycle ; Cell proliferation ; Cell survival ; Critical Care Medicine ; Cytokines ; Cytotoxicity ; Degradation ; Drug therapy ; Drug therapy, Combination ; Drugs ; G1 Phase Cell Cycle Checkpoints ; Genetic aspects ; Health aspects ; Hematology ; Humans ; Ikaros protein ; Ikaros Transcription Factor - analysis ; Ikaros Transcription Factor - genetics ; Immunomodulation ; In vitro methods and tests ; In vivo methods and tests ; Inhibition ; Inhibitors ; Intensive ; Interferon regulatory factor 4 ; Interferon Regulatory Factors - analysis ; Interferon Regulatory Factors - genetics ; Internal Medicine ; Isoxazoles - pharmacology ; Medicine ; Medicine & Public Health ; Mice ; Multiple myeloma ; Multiple Myeloma - drug therapy ; Multiple Myeloma - pathology ; Myc protein ; Nuclear Proteins - antagonists & inhibitors ; Oncology ; original-article ; Patients ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Proteins ; Proto-Oncogene Proteins c-myc - analysis ; Proto-Oncogene Proteins c-myc - genetics ; Rodents ; Stromal cells ; Synergism ; Terminal protein ; Testing ; Toxicity ; Transcription ; Transcription Factors - antagonists & inhibitors ; Tumors ; Xenografts ; Xenotransplantation</subject><ispartof>Leukemia, 2017-08, Vol.31 (8), p.1760-1769</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature. 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2017</rights><rights>Macmillan Publishers Limited, part of Springer Nature. 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-fc88f427b6730f4d894faff5d6e53d99d0ebe73bb228ee80bd50630c37e1d1073</citedby><cites>FETCH-LOGICAL-c549t-fc88f427b6730f4d894faff5d6e53d99d0ebe73bb228ee80bd50630c37e1d1073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2016.355$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2016.355$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27890933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siu, K T</creatorcontrib><creatorcontrib>Ramachandran, J</creatorcontrib><creatorcontrib>Yee, A J</creatorcontrib><creatorcontrib>Eda, H</creatorcontrib><creatorcontrib>Santo, L</creatorcontrib><creatorcontrib>Panaroni, C</creatorcontrib><creatorcontrib>Mertz, J A</creatorcontrib><creatorcontrib>Sims III, R J</creatorcontrib><creatorcontrib>Cooper, M R</creatorcontrib><creatorcontrib>Raje, N</creatorcontrib><title>Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of
MYC
transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G
1
cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the
in vivo
efficacy of CPI-0610 in a MM xenograft mouse model. Our study found
IKZF1
and
IRF4
to be among the primary targets of CPI-0610, along with
MYC
. Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show
in vitro
synergism, in part due to concomitant suppression of
IKZF1
,
IRF4
and
MYC
, providing a rationale for clinical testing of this drug combination in MM patients.</description><subject>13/2</subject><subject>13/31</subject><subject>38/39</subject><subject>38/77</subject><subject>38/89</subject><subject>45/22</subject><subject>631/67/1059/153</subject><subject>631/67/1990/804</subject><subject>631/92/436/108</subject><subject>64/60</subject><subject>692/308/2778</subject><subject>692/700/565/1436/1437</subject><subject>96/106</subject><subject>96/109</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Benzazepines - pharmacology</subject><subject>Binding proteins</subject><subject>Biocompatibility</subject><subject>Biotechnology</subject><subject>Bone marrow</subject><subject>Cancer Research</subject><subject>Caspase</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Cell survival</subject><subject>Critical Care Medicine</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Degradation</subject><subject>Drug therapy</subject><subject>Drug therapy, Combination</subject><subject>Drugs</subject><subject>G1 Phase Cell Cycle Checkpoints</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Humans</subject><subject>Ikaros protein</subject><subject>Ikaros Transcription Factor - analysis</subject><subject>Ikaros Transcription Factor - genetics</subject><subject>Immunomodulation</subject><subject>In vitro methods and tests</subject><subject>In vivo methods and tests</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Intensive</subject><subject>Interferon regulatory factor 4</subject><subject>Interferon Regulatory Factors - analysis</subject><subject>Interferon Regulatory Factors - genetics</subject><subject>Internal Medicine</subject><subject>Isoxazoles - pharmacology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - pathology</subject><subject>Myc protein</subject><subject>Nuclear Proteins - antagonists & inhibitors</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patients</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-myc - analysis</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Rodents</subject><subject>Stromal cells</subject><subject>Synergism</subject><subject>Terminal protein</subject><subject>Testing</subject><subject>Toxicity</subject><subject>Transcription</subject><subject>Transcription Factors - antagonists & inhibitors</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kl1rFDEUhgdR7Fq981oGBPGis-Zj8jGXZWm1ULAXeh0ymTPdlGSyJpni_gd_tBm3aitFQsgh5znvyQlvVb3GaI0RlR8czGuCMF9Txp5UK9wK3jDG8NNqhaQUDe9Ie1S9SOkGoSXJn1dHRMgOdZSuqh9XEYyzkzXa1dpke2vzvg5jvbm6aBDH6KTW9RRuwdXJa-caHxyY2UHdx-DDELy2U62noYbvOeomQ_R2Klq7GDKUlJ22trc5xBLVeQvLjnr3q4efXba7ouX34IrSy-rZqF2CV3fncfX1_OzL5lNz-fnjxeb0sjGs7XIzGinHloieC4rGdpBdO-pxZAMHRoeuGxD0IGjfEyIBJOoHhjhFhgrAA0aCHlfvD7rlkd9mSFl5mww4pycIc1JYti1lpEWyoG__QW_CHMuASRGOGaOEcfE_CneEYSmEYH-pa-1A2WkM5cfM0lqdctkRySVbOq4focoawFsTJhhtuX9Q8O5ewRa0y9sU3JxtmNJD8OQAmhhSijCqXbRex73CSC1eUsVLavGSKl4q-Ju7oebew_AH_m2eAjQHIJXUdA3x3tSPCf4EuMPRyA</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Siu, K T</creator><creator>Ramachandran, J</creator><creator>Yee, A J</creator><creator>Eda, H</creator><creator>Santo, L</creator><creator>Panaroni, C</creator><creator>Mertz, J A</creator><creator>Sims III, R J</creator><creator>Cooper, M R</creator><creator>Raje, N</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma</title><author>Siu, K T ; Ramachandran, J ; Yee, A J ; Eda, H ; Santo, L ; Panaroni, C ; Mertz, J A ; Sims III, R J ; Cooper, M R ; Raje, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-fc88f427b6730f4d894faff5d6e53d99d0ebe73bb228ee80bd50630c37e1d1073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/2</topic><topic>13/31</topic><topic>38/39</topic><topic>38/77</topic><topic>38/89</topic><topic>45/22</topic><topic>631/67/1059/153</topic><topic>631/67/1990/804</topic><topic>631/92/436/108</topic><topic>64/60</topic><topic>692/308/2778</topic><topic>692/700/565/1436/1437</topic><topic>96/106</topic><topic>96/109</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Benzazepines - pharmacology</topic><topic>Binding proteins</topic><topic>Biocompatibility</topic><topic>Biotechnology</topic><topic>Bone marrow</topic><topic>Cancer Research</topic><topic>Caspase</topic><topic>Cell cycle</topic><topic>Cell proliferation</topic><topic>Cell survival</topic><topic>Critical Care Medicine</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Degradation</topic><topic>Drug therapy</topic><topic>Drug therapy, Combination</topic><topic>Drugs</topic><topic>G1 Phase Cell Cycle Checkpoints</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Ikaros protein</topic><topic>Ikaros Transcription Factor - analysis</topic><topic>Ikaros Transcription Factor - genetics</topic><topic>Immunomodulation</topic><topic>In vitro methods and tests</topic><topic>In vivo methods and tests</topic><topic>Inhibition</topic><topic>Inhibitors</topic><topic>Intensive</topic><topic>Interferon regulatory factor 4</topic><topic>Interferon Regulatory Factors - analysis</topic><topic>Interferon Regulatory Factors - genetics</topic><topic>Internal Medicine</topic><topic>Isoxazoles - pharmacology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - pathology</topic><topic>Myc protein</topic><topic>Nuclear Proteins - antagonists & inhibitors</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patients</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-myc - analysis</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Rodents</topic><topic>Stromal cells</topic><topic>Synergism</topic><topic>Terminal protein</topic><topic>Testing</topic><topic>Toxicity</topic><topic>Transcription</topic><topic>Transcription Factors - antagonists & inhibitors</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siu, K T</creatorcontrib><creatorcontrib>Ramachandran, J</creatorcontrib><creatorcontrib>Yee, A J</creatorcontrib><creatorcontrib>Eda, H</creatorcontrib><creatorcontrib>Santo, L</creatorcontrib><creatorcontrib>Panaroni, C</creatorcontrib><creatorcontrib>Mertz, J A</creatorcontrib><creatorcontrib>Sims III, R J</creatorcontrib><creatorcontrib>Cooper, M R</creatorcontrib><creatorcontrib>Raje, N</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siu, K T</au><au>Ramachandran, J</au><au>Yee, A J</au><au>Eda, H</au><au>Santo, L</au><au>Panaroni, C</au><au>Mertz, J A</au><au>Sims III, R J</au><au>Cooper, M R</au><au>Raje, N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>31</volume><issue>8</issue><spage>1760</spage><epage>1769</epage><pages>1760-1769</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of
MYC
transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G
1
cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the
in vivo
efficacy of CPI-0610 in a MM xenograft mouse model. Our study found
IKZF1
and
IRF4
to be among the primary targets of CPI-0610, along with
MYC
. Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show
in vitro
synergism, in part due to concomitant suppression of
IKZF1
,
IRF4
and
MYC
, providing a rationale for clinical testing of this drug combination in MM patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27890933</pmid><doi>10.1038/leu.2016.355</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2017-08, Vol.31 (8), p.1760-1769 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1844352408 |
| source | MEDLINE; Nature; SpringerLink Journals - AutoHoldings |
| subjects | 13/2 13/31 38/39 38/77 38/89 45/22 631/67/1059/153 631/67/1990/804 631/92/436/108 64/60 692/308/2778 692/700/565/1436/1437 96/106 96/109 Animals Anticancer properties Antimitotic agents Antineoplastic agents Antitumor activity Apoptosis Benzazepines - pharmacology Binding proteins Biocompatibility Biotechnology Bone marrow Cancer Research Caspase Cell cycle Cell proliferation Cell survival Critical Care Medicine Cytokines Cytotoxicity Degradation Drug therapy Drug therapy, Combination Drugs G1 Phase Cell Cycle Checkpoints Genetic aspects Health aspects Hematology Humans Ikaros protein Ikaros Transcription Factor - analysis Ikaros Transcription Factor - genetics Immunomodulation In vitro methods and tests In vivo methods and tests Inhibition Inhibitors Intensive Interferon regulatory factor 4 Interferon Regulatory Factors - analysis Interferon Regulatory Factors - genetics Internal Medicine Isoxazoles - pharmacology Medicine Medicine & Public Health Mice Multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - pathology Myc protein Nuclear Proteins - antagonists & inhibitors Oncology original-article Patients Protein-Serine-Threonine Kinases - antagonists & inhibitors Proteins Proto-Oncogene Proteins c-myc - analysis Proto-Oncogene Proteins c-myc - genetics Rodents Stromal cells Synergism Terminal protein Testing Toxicity Transcription Transcription Factors - antagonists & inhibitors Tumors Xenografts Xenotransplantation |
| title | Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T12%3A05%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preclinical%20activity%20of%20CPI-0610,%20a%20novel%20small-molecule%20bromodomain%20and%20extra-terminal%20protein%20inhibitor%20in%20the%20therapy%20of%20multiple%20myeloma&rft.jtitle=Leukemia&rft.au=Siu,%20K%20T&rft.date=2017-08-01&rft.volume=31&rft.issue=8&rft.spage=1760&rft.epage=1769&rft.pages=1760-1769&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2016.355&rft_dat=%3Cgale_proqu%3EA689286858%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1925187775&rft_id=info:pmid/27890933&rft_galeid=A689286858&rfr_iscdi=true |