FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia
Acute Myeloid Leukaemia (AML) is a blood cancer, which affects the red blood cells in the bone marrow. Of the possible proteins that are affected in AML, fms-like tyrosine kinase 3 (FLT3) has long been recognized as a potential therapeutic target as it affects the other signaling pathways and leads...
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| Veröffentlicht in: | Bioinformation 2019, Vol.15 (2), p.104-115 |
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| creator | Gokhale, Padmini Chauhan, Aashish Pratap Singh Arora, Anushka Khandekar, Natasha Nayarisseri, Anuraj Singh, Sanjeev Kumar |
| description | Acute Myeloid Leukaemia (AML) is a blood cancer, which affects the red blood cells in the bone marrow. Of the possible proteins that are affected in AML, fms-like tyrosine kinase 3 (FLT3) has long been recognized as a potential therapeutic target as it affects the other signaling pathways and leads to a cascade of events. First-generation inhibitors sorafenib and midostaurin, as well as secondgeneration agents such as quizartinib and crenolanib are known. It is of interest to identify new compounds against FLT3 with improved activity using molecular docking and virtual screening. Molecular docking of existing inhibitors selected a top scoring bestestablished candidate Quizartinib having PubChem CID: 24889392. Similarity searching resulted in compound XGIQBUNWFCCMASUHFFFAOYSA-NPubChemCID: 44598530 which shows higher affinity scores. A comparative study of both the compounds using a drug-drug comparison, ADMET studies, boiled egg plot and pharmacophore parameters and properties confirmed the result and predicted the ligand to be an efficient inhibitor of FLT3. |
| doi_str_mv | 10.6026/97320630015104 |
| format | Article |
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Of the possible proteins that are affected in AML, fms-like tyrosine kinase 3 (FLT3) has long been recognized as a potential therapeutic target as it affects the other signaling pathways and leads to a cascade of events. First-generation inhibitors sorafenib and midostaurin, as well as secondgeneration agents such as quizartinib and crenolanib are known. It is of interest to identify new compounds against FLT3 with improved activity using molecular docking and virtual screening. Molecular docking of existing inhibitors selected a top scoring bestestablished candidate Quizartinib having PubChem CID: 24889392. Similarity searching resulted in compound XGIQBUNWFCCMASUHFFFAOYSA-NPubChemCID: 44598530 which shows higher affinity scores. A comparative study of both the compounds using a drug-drug comparison, ADMET studies, boiled egg plot and pharmacophore parameters and properties confirmed the result and predicted the ligand to be an efficient inhibitor of FLT3.</description><identifier>ISSN: 0973-2063</identifier><identifier>ISSN: 0973-8894</identifier><identifier>EISSN: 0973-2063</identifier><identifier>DOI: 10.6026/97320630015104</identifier><identifier>PMID: 31435156</identifier><language>eng</language><publisher>Singapore: Biomedical Informatics</publisher><subject>Acute myeloid leukemia ; Bone cancer ; Bone marrow ; Cancer ; Comparative studies ; Erythrocytes ; Flt3 protein ; Inhibitors ; Kinases ; Leukemia ; Molecular docking ; Myeloid leukemia ; Pharmacology ; Protein-tyrosine kinase ; Proteins ; Screening ; Therapeutic applications ; Tyrosine</subject><ispartof>Bioinformation, 2019, Vol.15 (2), p.104-115</ispartof><rights>Copyright Biomedical Informatics 2019</rights><rights>2019 Biomedical Informatics 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c348t-3f5cb2d1c59229b521404c683178b7e4826323f937e6396cb15f83eaa763778a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677903/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677903/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31435156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gokhale, Padmini</creatorcontrib><creatorcontrib>Chauhan, Aashish Pratap Singh</creatorcontrib><creatorcontrib>Arora, Anushka</creatorcontrib><creatorcontrib>Khandekar, Natasha</creatorcontrib><creatorcontrib>Nayarisseri, Anuraj</creatorcontrib><creatorcontrib>Singh, Sanjeev Kumar</creatorcontrib><creatorcontrib>In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, India</creatorcontrib><title>FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia</title><title>Bioinformation</title><addtitle>Bioinformation</addtitle><description>Acute Myeloid Leukaemia (AML) is a blood cancer, which affects the red blood cells in the bone marrow. 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A comparative study of both the compounds using a drug-drug comparison, ADMET studies, boiled egg plot and pharmacophore parameters and properties confirmed the result and predicted the ligand to be an efficient inhibitor of FLT3.</description><subject>Acute myeloid leukemia</subject><subject>Bone cancer</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Comparative studies</subject><subject>Erythrocytes</subject><subject>Flt3 protein</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Molecular docking</subject><subject>Myeloid leukemia</subject><subject>Pharmacology</subject><subject>Protein-tyrosine kinase</subject><subject>Proteins</subject><subject>Screening</subject><subject>Therapeutic applications</subject><subject>Tyrosine</subject><issn>0973-2063</issn><issn>0973-8894</issn><issn>0973-2063</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkUtLxDAURoMovrcupeDGzWiS2ybNRpDBFwy40XVM09sxmjaaNIL_3g4-UFcJJ-d-5PIRcsDoiaBcnCoJnAqglFWMlmtkm05ktkLrv-5bZCelJ0pLJmW1SbaAlVCxSmyTh8vFHRRueHSNG0MsWkxuORQ5uWFZ9MGjzd5MONjnFWlMwrZ4c3HMxhfJRsRhxbtp1Ng8YtG_ow-uLTzmZ-yd2SMbnfEJ97_OXXJ_eXE3v54tbq9u5ueLmYWyHmfQVbbhLbOV4lw1FWclLa2ogcm6kVjWXACHToFEAUrYhlVdDWiMFCBlbWCXnH3mvuSmx9biMEbj9Ut0vYnvOhin_74M7lEvw5sWQkpFYQo4_gqI4TVjGnXvkkXvzYAhJ80BhKoFZWJSj_6pTyHHYVpPc84oKKmYmqyTT8vGkFLE7uczjOpVefpvedPA4e8VfvTvtuADNseUFg</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Gokhale, Padmini</creator><creator>Chauhan, Aashish Pratap Singh</creator><creator>Arora, Anushka</creator><creator>Khandekar, Natasha</creator><creator>Nayarisseri, Anuraj</creator><creator>Singh, Sanjeev Kumar</creator><general>Biomedical Informatics</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>2019</creationdate><title>FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia</title><author>Gokhale, Padmini ; 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Of the possible proteins that are affected in AML, fms-like tyrosine kinase 3 (FLT3) has long been recognized as a potential therapeutic target as it affects the other signaling pathways and leads to a cascade of events. First-generation inhibitors sorafenib and midostaurin, as well as secondgeneration agents such as quizartinib and crenolanib are known. It is of interest to identify new compounds against FLT3 with improved activity using molecular docking and virtual screening. Molecular docking of existing inhibitors selected a top scoring bestestablished candidate Quizartinib having PubChem CID: 24889392. Similarity searching resulted in compound XGIQBUNWFCCMASUHFFFAOYSA-NPubChemCID: 44598530 which shows higher affinity scores. 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| subjects | Acute myeloid leukemia Bone cancer Bone marrow Cancer Comparative studies Erythrocytes Flt3 protein Inhibitors Kinases Leukemia Molecular docking Myeloid leukemia Pharmacology Protein-tyrosine kinase Proteins Screening Therapeutic applications Tyrosine |
| title | FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia |
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