Adavosertib

Adavosertib : Inhibitor, ATP competitive of WEE1

Structure

Information

Protein target names: WEE1

Mechanism of action: Inhibitor, ATP competitive

Recommended in-cell concentration:
30-100 nM or 300 nM (alone)

Reviewer recommended in-cell concentration: 300-1000 nM

In Vitro Validations

Uniprot ID: P30291
Target Class: Protein kinase
Target SubClass: Ser/Thr Protein Kinase
Potency: IC50
Potency Value: 5.2 nM
Potency Assay: Radioactive in vitro Kinase assay
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: no
Target aliases:
Wee1-like protein kinase, WEE1, WEE1_HUMAN, WEE1hu ...

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 10 Dec 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

MK-1775 (Adavosertib) is a potent inhibitor of Wee1 and Wee2, with off target biochemical and cellular activity on a number of other kinases, including polo-like kinase-1 (PLK1).

(last updated: 14 Dec 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

Adavosertib unarguably displays both potent WEE1 kinase affinity and a strong phenotype when in combination with common chemotherapies in vivo. However there are studies since published (10.1021/acschembio.7b00147, 10.1021/acs.jmedchem.7b00996) that demonstrate that this molecule has potent binding affinity for both WEE2 and PLK1. PLK1 is directly upstream of WEE1, acts as a negative regulator of active WEE1 amongst a myriad of other signalling roles and it’s inhibition by adavosertib likely plays a role (in addition to WEE1 inhibition) in this molecule’s cellular effects. Therefore, whilst this compound shows good broad selectivity across the kinome, it does have some specific liabilities that undermine its use as a chemical probe for furthering the understanding and consequences of WEE1 perturbation alone or even WEE kinases more broadly.

(last updated: 21 Dec 2020 )