2019
DOI: 10.1158/1535-7163.mct-18-0529
|View full text |Cite
|
Sign up to set email alerts
|

Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Abstract: Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/ C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by … Show more

Help me understand this report
View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

1
23
0

Year Published

2020
2020
2023
2023

Publication Types

Select...
8
1

Relationship

0
9

Authors

Journals

citations
Cited by 38 publications
(30 citation statements)
references
References 48 publications
1
23
0
Order By: Relevance
“…AKIs in preclinical studies In recent years, several small molecules that selectively target AURKA have been identified with anticancer activity in preclinical studies including LY3295668 [86], BPR1K0609S1 [81,82], LDD970 [83], MK-8745 [84,85], AKI603 [80] and CYC3 [79]. The detailed information is shown in Table 3.…”
Section: Specific Akismentioning
confidence: 99%
“…AKIs in preclinical studies In recent years, several small molecules that selectively target AURKA have been identified with anticancer activity in preclinical studies including LY3295668 [86], BPR1K0609S1 [81,82], LDD970 [83], MK-8745 [84,85], AKI603 [80] and CYC3 [79]. The detailed information is shown in Table 3.…”
Section: Specific Akismentioning
confidence: 99%
“…Indeed, all the Aurora-A inhibitors that have entered clinical trials act as ATP-competitors in the active site pocket, which is highly conserved among human kinases. Despite great efficacy (MLN8237 [ 80 ]), increased selectivity (LY3295668 [ 81 ]) and elevated potency (MK-5108 has an IC 50 of 0.064 nM [ 82 ]), the ATP-competitive inhibitors are well known for exhibiting high promiscuity [ 83 85 ]. To date, they have not met expectations raised in cellular studies.…”
Section: Targeting Aurora-a Kinase-independent Functions: a New Therapeutic Challengementioning
confidence: 99%
“…Marked N-myc loss was observed with 24 hours of CD532 treatment in vitro , and CD532 treatment of a NBL xenograft confirmed N-myc loss [30] . Recently LY3295668, another AURKA inhibitor (AURKAi), showed similar phenotypic effects to Alisertib in preclinical cancer models and now is being assessed in children with relapsed/refractory NBL [NCT04106219] [31] . Its specific effects on MYCN have not yet been reported, but together these data suggest that clinically relevant AURKAi can have a N-myc-destabilizing effect.…”
Section: Introductionmentioning
confidence: 99%