CasNo.955365-80-7,Adavosertib (MK-1775),(955365-80-7) Suppliers

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Purity: >97%

Keywords

Adavosertib (MK-1775) AZD1775 955365-80-7

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Biological Activity

Description

Adavosertib (MK-1775, AZD1775) is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.

Features

The first reported Wee1 inhibitor.

Targets

Wee1 [1]
(Cell-free assay)

5.2 nM

In vitro

MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells. [1]

Cell Data

Cell Lines	Assay Type	Activity Description	PMID
ASPC-1	Growth Inhibition Assay	IC50=13.2 ± 1.1 μM	25458954
BxPC-3	Growth Inhibition Assay	IC50=0.8 ± 0.03 μM	25458954
CFPAC-1	Growth Inhibition Assay	IC50=3.3 ± 0.2 μM	25458954

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-Cdk1(Y15) / Cdk1; p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345); PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15); WEE1;	25609063 25458954 27616351
Immunofluorescence	tubulin / p-HH3(S10); γH2AX; Cleaved caspase-3 / pH3;	30755439 25609063 27616351
Growth inhibition assay	Cell viability; IC50;	25458954 25084614

In vivo

MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models is also moderate. [1]