Repurposing clinically approved drugs as Wee1 checkpoint kinase inhibitors: an <i>in silico</i> investigation integrating molecular docking, ensemble QSAR modelling and molecular dynamics simulation

Olawale, Femi; Ogunyemi, Oludare M.; Folorunso, Ibukun Mary

doi:10.1080/08927022.2022.2101673

Cited by 1 publication

(4 citation statements)

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“…144 Olawale et al performed in silico studies using FDA-approved drugs and proposed Dasatinib and Cangrelor as potential repurposed WEE1i. 145 PF03814735 ( 6) is an Aurora kinase inhibitor in clinical trials. It showed nanomolar WEE1 inhibition (IC 50 = 78.7 nM).…”

Section: Synthesis Of Pyrazolopyrimidine Analoguesmentioning

confidence: 99%

“…Yang et al were the first to identify the rhodium(III) complex 9 , which induces mitotic catastrophe via induced DNA damage, as a potent single agent WEE1i in TP53 mutant (MDA-MB-231) cells . Olawale et al performed in silico studies using FDA-approved drugs and proposed Dasatinib and Cangrelor as potential repurposed WEE1i …”

Section: Small Molecule Inhibitors Of Wee1 Kinasementioning

confidence: 99%

“…He proposed using either shorter or longer linkers but not intermediate ones. The proposed degraders MA055 (143) and MA071 (145) have indeed shown increased selectivity but no apparent change in apoptosis or antiproliferative effects compared to AZD1775. 156 Similar results were obtained by Zhu et al in in vitro studies of 144, a PROTAC degrader constructed using AZD1775 and CRBN E3 ligase recruiter and in vivo studies using MV-4−11 cells showed good WEE1 degradation in the target site after 3 h treatment.…”

Section: Degraders Of Wee1 Kinasementioning

confidence: 99%

“… 144 Olawale et al performed in silico studies using FDA-approved drugs and proposed Dasatinib and Cangrelor as potential repurposed WEE1i. 145 …”

Section: Small Molecule Inhibitors Of Wee1 Kinasementioning

confidence: 99%

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Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders

et al. 2023

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WEE1 is a checkpoint kinase critical for mitotic events, especially in cell maturation and DNA repair. Most cancer cells' progression and survival are linked with elevated levels of WEE1 kinase. Thus, WEE1 kinase has become a new promising druggable target. A few classes of WEE1 inhibitors are designed by rationale or structure-based techniques and optimization approaches to identify selective acting anticancer agents. The discovery of the WEE1 inhibitor AZD1775 further emphasized WEE1 as a promising anticancer target. Therefore, the current review provides a comprehensive data on medicinal chemistry, synthetic approaches, optimization methods, and the interaction profile of WEE1 kinase inhibitors. In addition, WEE1 PROTAC degraders and their synthetic procedures, including a list of noncoding RNAs necessary for regulation of WEE1, are also highlighted. From the standpoint of medicinal chemistry, the contents of this compilation serve as an exemplar for the further design, synthesis, and optimization of promising WEE1-targeted anticancer agents.

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Section: Synthesis Of Pyrazolopyrimidine Analoguesmentioning

confidence: 99%

Section: Small Molecule Inhibitors Of Wee1 Kinasementioning

confidence: 99%