{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7(52)"],"submitter":["Hsu YC"],"pubmed_abstract":["The design and synthesis of a quinazoline-based, multi-kinase inhibitor for the treatment of acute myeloid leukemia (AML) and other malignancies is reported. Based on the previously reported furanopyrimidine 3, quinazoline core containing lead 4 was synthesized and found to impart dual FLT3/AURKA inhibition (IC50 = 127/5 nM), as well as improved physicochemical properties. A detailed structure-activity relationship study of the lead 4 allowed FLT3 and AURKA inhibition to be finely tuned, resulting in AURKA selective (5 and 7; 100-fold selective over FLT3), FLT3 selective (13; 30-fold selective over AURKA) and dual FLT3/AURKA selective (BPR1K871; IC50 = 19/22 nM) agents. BPR1K871 showed potent anti-proliferative activities in MOLM-13 and MV4-11 AML cells (EC50 ~ 5 nM). Moreover, kinase prof"],"journal":["Oncotarget"],"pagination":["86239-86256"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5349910"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of BPR1K871, a quinazoline based, multi-kinase inhibitor for the treatment of AML and solid tumors: Rational design, synthesis, in vitro and in vivo evaluation."],"pmcid":["PMC5349910"],"pubmed_authors":["Chen PY","Coumar MS","Wang SY","Wu MH","Chang CW","Yeh TK","Ke YY","Lin WH","Li AS","Huang CL","Kuo PC","Chen CT","Song JS","Yen KJ","Chang YI","Kuo CC","Chen CP","Hsu YC","Hsu JT","Wang WC","Hsieh HP","Chen CH","Shiao HY","Shih C","Kuo FM"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of BPR1K871, a quinazoline based, multi-kinase inhibitor for the treatment of AML and solid tumors: Rational design, synthesis, in vitro and in vivo evaluation.","description":"The design and synthesis of a quinazoline-based, multi-kinase inhibitor for the treatment of acute myeloid leukemia (AML) and other malignancies is reported. Based on the previously reported furanopyrimidine 3, quinazoline core containing lead 4 was synthesized and found to impart dual FLT3/AURKA inhibition (IC50 = 127/5 nM), as well as improved physicochemical properties. A detailed structure-activity relationship study of the lead 4 allowed FLT3 and AURKA inhibition to be finely tuned, resulting in AURKA selective (5 and 7; 100-fold selective over FLT3), FLT3 selective (13; 30-fold selective over AURKA) and dual FLT3/AURKA selective (BPR1K871; IC50 = 19/22 nM) agents. BPR1K871 showed potent anti-proliferative activities in MOLM-13 and MV4-11 AML cells (EC50 ~ 5 nM). Moreover, kinase prof","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Dec","modification":"2026-05-05T18:23:19.78Z","creation":"2019-03-27T02:38:38Z"},"accession":"S-EPMC5349910","cross_references":{"pubmed":["27863392"],"doi":["10.18632/oncotarget.13369"]}}