MK-1775 LAPIS kinase inhibitor est de Wee1 (IC50 = 5.2 nM).1 phosphorylationem Cdc2 in tryosine-15 . inhibere ostensum est, quae G2 DNA damnum checkpoint.1 In p53 deficientibus tumoribus qui unice confidunt in G2 LAPIS super DNA damnum abrogat., MK-1775, respectu DNA damno chemotherapeutic agentium, nuntiavit apoptosin in vitro inducere et potentiare inhibitionis tumoris in vivo.
MK-1775 curatio ad inhibitionem Wee1 kinasis deductam et phosphorylationem inhibendi substrati Cdc2 reductam.. MK-1775, cum dosed cum gemcitabine, LAPIS comprehensio ad promovendum ingressum mitoticum et faciliorem tumorem cellae mortis abrogavit, comparatus ad imperium et gemcitabinum tumores tractatos.. MK-1775 Monotherapia tumorem regressuum non induxit. tamen, Coniunctio gemcitabinarum cum MK-1775 productae activitatis anti-tumoris robusti et insigniter aucta responsionis tumoris regressionis (4.01 complicare) comparari curatio gemcitabina in tumoribus deficientibus p53. Tumor rursus incrementum curvarum post periodum curationis medicamento machinatae innuunt effectum therapiae combinationis longiorem esse quam gemcitabinum.. Nulla agentium regressuum tumorem in p53-ferae generis xenografts produxit.
MK-1775 vetat Wee1 kinase in ATP-competitive modo. Comparari Wee1, MK-1775 repraesentationes 2- Ad III-ovili minoris potentia contra Ita cum IC50 of * 14 nM, 10-complicare minori potentia contra septem alias kinases cum >80% inhibitionis ad 1 μM, et >100-complicare selectivity in hominum Myt 1, alterum kinase quod cyclin-dependens kinase vetat 1 (CDC2) per phosphorylation ad alterius loci (Thr14).
Abrogando DNA damnum LAPIS per obsidionem Wee1 activitatem in Widr cellulis p53 mutatum afferentem, curatio MK-1775 vetat phosphorylationem basalem CDC2 ad Tyr15 (CD2Y15) cum EC50 of * 49 nM, et supprimit gemcitabine-, carboplatin- vel cisplatin effecerunt phosphorylation CDC2 et cycli cellulae comprehensionis in modo dosi-dependens, cum EC50 of * 82 nM and * 81 nM, 180 nM and * 163 nM, tum 159 nM and * 160 nM, respectively. MK-1775 curatio sola at 30-100 nM nullum effectum antiproliferivum significant in cellulis Widr et H1299, at MK-1775 300 nM, satis inhibere Wee1 by >80%, modice sed significant effectus antiprolifeative ostendit per 34.1% in WiDr cellulis ac 28.4% H1299 in cellulis.
