FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225349723> ?p ?o ?g. }

• W4225349723 endingPage "5744" @default.
• W4225349723 startingPage "5733" @default.
• W4225349723 abstract "Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin-CD34+CD38-), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. SIGNIFICANCE: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells." @default.
• W4225349723 created "2022-05-05" @default.
• W4225349723 creator A5001428904 @default.
• W4225349723 creator A5005502949 @default.
• W4225349723 creator A5005838619 @default.
• W4225349723 creator A5006061477 @default.
• W4225349723 creator A5008987022 @default.
• W4225349723 creator A5009803654 @default.
• W4225349723 creator A5011443121 @default.
• W4225349723 creator A5011888770 @default.
• W4225349723 creator A5013277256 @default.
• W4225349723 creator A5022158812 @default.
• W4225349723 creator A5026009554 @default.
• W4225349723 creator A5029296072 @default.
• W4225349723 creator A5033032488 @default.
• W4225349723 creator A5038189076 @default.
• W4225349723 creator A5040725620 @default.
• W4225349723 creator A5041097509 @default.
• W4225349723 creator A5043757560 @default.
• W4225349723 creator A5046790715 @default.
• W4225349723 creator A5048624339 @default.
• W4225349723 creator A5051159339 @default.
• W4225349723 creator A5057007717 @default.
• W4225349723 creator A5062247953 @default.
• W4225349723 creator A5065158992 @default.
• W4225349723 creator A5067442100 @default.
• W4225349723 creator A5071240532 @default.
• W4225349723 creator A5073812413 @default.
• W4225349723 creator A5074033554 @default.
• W4225349723 creator A5083355763 @default.
• W4225349723 creator A5084798379 @default.
• W4225349723 creator A5085546344 @default.
• W4225349723 creator A5086430791 @default.
• W4225349723 creator A5086792779 @default.
• W4225349723 date "2021-09-30" @default.
• W4225349723 modified "2023-10-10" @default.
• W4225349723 title "MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia" @default.
• W4225349723 cites W1691578538 @default.
• W4225349723 cites W1696775091 @default.
• W4225349723 cites W1836407057 @default.
• W4225349723 cites W1980401099 @default.
• W4225349723 cites W1980904297 @default.
• W4225349723 cites W1981258651 @default.
• W4225349723 cites W1983641075 @default.
• W4225349723 cites W1984301575 @default.
• W4225349723 cites W1985197354 @default.
• W4225349723 cites W1992424565 @default.
• W4225349723 cites W2004142027 @default.
• W4225349723 cites W2009886857 @default.
• W4225349723 cites W2040392840 @default.
• W4225349723 cites W2042077985 @default.
• W4225349723 cites W2062069198 @default.
• W4225349723 cites W2066980817 @default.
• W4225349723 cites W2068452253 @default.
• W4225349723 cites W2090982381 @default.
• W4225349723 cites W2094035951 @default.
• W4225349723 cites W2115517051 @default.
• W4225349723 cites W2175970000 @default.
• W4225349723 cites W2281603397 @default.
• W4225349723 cites W2321911014 @default.
• W4225349723 cites W2404941902 @default.
• W4225349723 cites W2409723809 @default.
• W4225349723 cites W2461427403 @default.
• W4225349723 cites W2482744592 @default.
• W4225349723 cites W2552471681 @default.
• W4225349723 cites W2553658634 @default.
• W4225349723 cites W2559537906 @default.
• W4225349723 cites W2610081389 @default.
• W4225349723 cites W2612974116 @default.
• W4225349723 cites W2737915130 @default.
• W4225349723 cites W2795342601 @default.
• W4225349723 cites W2883488800 @default.
• W4225349723 cites W2915183228 @default.
• W4225349723 cites W2955594941 @default.
• W4225349723 cites W2960155897 @default.
• W4225349723 cites W2969237687 @default.
• W4225349723 cites W2990405666 @default.
• W4225349723 cites W2991199300 @default.
• W4225349723 cites W2999324060 @default.
• W4225349723 cites W3010017539 @default.
• W4225349723 cites W3016506948 @default.
• W4225349723 cites W3029741569 @default.
• W4225349723 cites W3147625776 @default.
• W4225349723 cites W4312790597 @default.
• W4225349723 cites W765687508 @default.
• W4225349723 doi "https://doi.org/10.1158/0008-5472.can-21-0061" @default.
• W4225349723 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34593524" @default.
• W4225349723 hasPublicationYear "2021" @default.
• W4225349723 type Work @default.
• W4225349723 citedByCount "8" @default.
• W4225349723 countsByYear W42253497232021 @default.
• W4225349723 countsByYear W42253497232022 @default.
• W4225349723 countsByYear W42253497232023 @default.
• W4225349723 crossrefType "journal-article" @default.
• W4225349723 hasAuthorship W4225349723A5001428904 @default.
• W4225349723 hasAuthorship W4225349723A5005502949 @default.
• W4225349723 hasAuthorship W4225349723A5005838619 @default.
• W4225349723 hasAuthorship W4225349723A5006061477 @default.

• next