AZD2014

ATP-competitive inhibitor of MTOR

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

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Information

MTOR

ATP-competitive inhibitor

10 nM - 2 uM

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Probe Availability:

In Vitro Validations

Uniprot ID: P42345

Target Class: Kinase

Target SubClass: Atypical

Potency: IC50

Potency Value: 2.8 nM

Potency Assay: Inhibition of mTOR kinase was evaluated in a high-throughput assay using α screen capture complex technology (Perkin-Elmer) with a recombinant truncated FLAG-tagged mTOR (amino acids 1362–2549, expressed in HEK293 cells).

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Serine/threonine-protein kinase mTOR, RAPT1, RAFT1 ...

DOI Reference: 10.1158/1535-7163.MCT-15-0365

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): The activity of the lipid kinases, class I PI3Ks α, β, γ, δ was measured with the lipid PIP2 as substrate. AZD2014 was inactive against 200 additional kinases at 10 uM. AZD2014 is >1,000-fold selective for mTOR kinases over PI3K kinases (Ambit assay). In panels of 220 and 393 kinases, WNK2 was the only off-target hit with >50% inhibition and 10 uM, and minimal off-target binding was detected at 1 uM (Dudee and Millipore assays).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 27 May 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Selectivity over 200 typical protein kinases and PI3Ks is >1000X. However, selectivity over atypical lipid-like protein kinases (e.g., ATM, ATR, DNA-PK) does not appear to have been disclosed, and this leaves outstanding selectivity concerns. In terms of the probe's use in cell-based assays, AZD8055 - a close analog - may be preferred, with potencies 5-10X greater than AZD2014. WYE-125132 may also be a preferable cell-based probe, with apparent superior cell-based potency over AZD2014, and reported >5000X selectivity over PI3Ks and some representative atypical protein kinases (ATR, hSMG1). With high bioavailability and low clearance in mice, AZD2014 is appropriate for human tumor xenograft models in mice; however, potency against murine mTor does not appear to have been disclosed. Suitability of the probe for use in a pure mouse model is unclear.

(last updated: 1 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 5 Jan 2017 )