E-viri
Recenzirano
Odprti dostop
-
Krivtsov, Andrei V.; Evans, Kathryn; Gadrey, Jayant Y.; Eschle, Benjamin K.; Hatton, Charlie; Uckelmann, Hannah J.; Ross, Kenneth N.; Perner, Florian; Olsen, Sarah N.; Pritchard, Tara; McDermott, Lisa; Jones, Connor D.; Jing, Duohui; Braytee, Ali; Chacon, Diego; Earley, Eric; McKeever, Brian M.; Claremon, David; Gifford, Andrew J.; Lee, Heather J.; Teicher, Beverly A.; Pimanda, John E.; Beck, Dominik; Perry, Jennifer A.; Smith, Malcolm A.; McGeehan, Gerard M.; Lock, Richard B.; Armstrong, Scott A.
Cancer cell, 12/2019, Letnik: 36, Številka: 6Journal Article
Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective, and orally bioavailable small-molecule inhibitor VTP50469. Cell lines carrying MLL rearrangements were selectively responsive to VTP50469. VTP50469 displaced Menin from protein complexes and inhibited chromatin occupancy of MLL at select genes. Loss of MLL binding led to changes in gene expression, differentiation, and apoptosis. Patient-derived xenograft (PDX) models derived from patients with either MLL-r acute myeloid leukemia or MLL-r acute lymphoblastic leukemia (ALL) showed dramatic reductions of leukemia burden when treated with VTP50469. Multiple mice engrafted with MLL-r ALL remained disease free for more than 1 year after treatment. These data support rapid translation of this approach to clinical trials. Display omitted •A selective, orally bioavailable Menin-MLL inhibitor, VTP50469, is developed•Displacement of Menin from chromatin leads to loss of MLL from specific loci•Treatment with VTP50469 leads to suppression of a subset of MLL fusion target genes•Treatment with VTP50469 improves survival in PDX models of MLL-r ALL Krivtsov et al. develop a selective and orally bioavailable small-molecule inhibitor targeting the Menin-MLL interaction, which suppresses a subset of MLL fusion target genes and significantly improves survival in PDX models of MLL-rearranged leukemia.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.