Matches in SemOpenAlex for { <https://semopenalex.org/work/W4226269696> ?p ?o ?g. }
- W4226269696 endingPage "2328" @default.
- W4226269696 startingPage "2317" @default.
- W4226269696 abstract "The protein arginine methyltransferase 5 (PRMT5) methylates a variety of proteins involved in splicing, multiple signal transduction pathways, epigenetic control of gene expression, and mechanisms leading to protein expression required for cellular proliferation. Dysregulation of PRMT5 is associated with clinical features of several cancers, including lymphomas, lung cancer, and breast cancer. Here, we describe the characterization of JNJ-64619178, a novel, selective, and potent PRMT5 inhibitor, currently in clinical trials for patients with advanced solid tumors, non-Hodgkin's lymphoma, and lower-risk myelodysplastic syndrome. JNJ-64619178 demonstrated a prolonged inhibition of PRMT5 and potent antiproliferative activity in subsets of cancer cell lines derived from various histologies, including lung, breast, pancreatic, and hematological malignancies. In primary acute myelogenous leukemia samples, the presence of splicing factor mutations correlated with a higher ex vivo sensitivity to JNJ-64619178. Furthermore, the potent and unique mechanism of inhibition of JNJ-64619178, combined with highly optimized pharmacological properties, led to efficient tumor growth inhibition and regression in several xenograft models in vivo, with once-daily or intermittent oral-dosing schedules. An increase in splicing burden was observed upon JNJ-64619178 treatment. Overall, these observations support the continued clinical evaluation of JNJ-64619178 in patients with aberrant PRMT5 activity-driven tumors." @default.
- W4226269696 created "2022-05-05" @default.
- W4226269696 creator A5000261087 @default.
- W4226269696 creator A5000475648 @default.
- W4226269696 creator A5000928333 @default.
- W4226269696 creator A5001032583 @default.
- W4226269696 creator A5003237265 @default.
- W4226269696 creator A5005553209 @default.
- W4226269696 creator A5005659795 @default.
- W4226269696 creator A5006068513 @default.
- W4226269696 creator A5008270091 @default.
- W4226269696 creator A5009013904 @default.
- W4226269696 creator A5015073949 @default.
- W4226269696 creator A5015576679 @default.
- W4226269696 creator A5019565101 @default.
- W4226269696 creator A5021564306 @default.
- W4226269696 creator A5021620461 @default.
- W4226269696 creator A5022151581 @default.
- W4226269696 creator A5022261026 @default.
- W4226269696 creator A5023701680 @default.
- W4226269696 creator A5026129104 @default.
- W4226269696 creator A5028156716 @default.
- W4226269696 creator A5030082945 @default.
- W4226269696 creator A5032408543 @default.
- W4226269696 creator A5039662809 @default.
- W4226269696 creator A5043253847 @default.
- W4226269696 creator A5047840816 @default.
- W4226269696 creator A5048152285 @default.
- W4226269696 creator A5052840616 @default.
- W4226269696 creator A5056472309 @default.
- W4226269696 creator A5056921013 @default.
- W4226269696 creator A5056983974 @default.
- W4226269696 creator A5059325122 @default.
- W4226269696 creator A5061125875 @default.
- W4226269696 creator A5064569147 @default.
- W4226269696 creator A5064747201 @default.
- W4226269696 creator A5076755054 @default.
- W4226269696 creator A5079652359 @default.
- W4226269696 creator A5079889024 @default.
- W4226269696 creator A5086137134 @default.
- W4226269696 creator A5089611613 @default.
- W4226269696 date "2021-09-28" @default.
- W4226269696 modified "2023-10-05" @default.
- W4226269696 title "Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity" @default.
- W4226269696 cites W1966509827 @default.
- W4226269696 cites W1967668937 @default.
- W4226269696 cites W2026542427 @default.
- W4226269696 cites W2033295584 @default.
- W4226269696 cites W2044474286 @default.
- W4226269696 cites W2071576183 @default.
- W4226269696 cites W2081604575 @default.
- W4226269696 cites W2082262146 @default.
- W4226269696 cites W2108853871 @default.
- W4226269696 cites W2120192934 @default.
- W4226269696 cites W2125049252 @default.
- W4226269696 cites W2126496132 @default.
- W4226269696 cites W2131321938 @default.
- W4226269696 cites W2132341258 @default.
- W4226269696 cites W2179442157 @default.
- W4226269696 cites W2183089903 @default.
- W4226269696 cites W2183418069 @default.
- W4226269696 cites W2263928505 @default.
- W4226269696 cites W2321587450 @default.
- W4226269696 cites W2330712912 @default.
- W4226269696 cites W2346030347 @default.
- W4226269696 cites W241169641 @default.
- W4226269696 cites W2468475414 @default.
- W4226269696 cites W2481207274 @default.
- W4226269696 cites W2515668871 @default.
- W4226269696 cites W2570732803 @default.
- W4226269696 cites W2591059370 @default.
- W4226269696 cites W2732772919 @default.
- W4226269696 cites W2758475630 @default.
- W4226269696 cites W2795877840 @default.
- W4226269696 cites W2800877169 @default.
- W4226269696 cites W2890885925 @default.
- W4226269696 cites W2901534288 @default.
- W4226269696 cites W2901706397 @default.
- W4226269696 cites W2908855808 @default.
- W4226269696 cites W2922748901 @default.
- W4226269696 cites W2947535546 @default.
- W4226269696 cites W2949815414 @default.
- W4226269696 cites W2964739845 @default.
- W4226269696 cites W2965551559 @default.
- W4226269696 cites W2979332595 @default.
- W4226269696 cites W2980561200 @default.
- W4226269696 cites W3005836543 @default.
- W4226269696 cites W3044762253 @default.
- W4226269696 cites W3048193465 @default.
- W4226269696 cites W3089571682 @default.
- W4226269696 cites W3136769376 @default.
- W4226269696 cites W3139197589 @default.
- W4226269696 cites W3175104012 @default.
- W4226269696 cites W4246440824 @default.
- W4226269696 doi "https://doi.org/10.1158/1535-7163.mct-21-0367" @default.
- W4226269696 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34583982" @default.
- W4226269696 hasPublicationYear "2021" @default.
- W4226269696 type Work @default.