2-MT 63

Inhibitor of TEK

Structure

Information

Protein target names: TEK

Mechanism of action: Inhibitor

In Vitro Validations

Uniprot ID: Q02763
Target Class: Protein kinase
Target SubClass: TK
Potency: IC50
Potency Value: 30 nM
Potency Assay: Homogenous time-resolved fluorescence assays detecting enzyme activity using peptide substrates.
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes, see J Med Chem paper.
Target aliases:
Angiopoietin-1 receptor, VMCM1, VMCM, TIE2, TEK, T ...

In Cell Validations

In Vivo Data

Reagent authentication certificate: PDF image

I have extra information to add

SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

2-MT 63 represents a novel inhibitor of the TIE2 receptor. There are multiple kinase inhibitors that have validated activity versus the TIE2 receptor including the advanced clinical agents, Sitravatinib, Glesatinib and Rebastinib. This agent is a useful tool given its unique polypharmacological profile (Rebastinib, for instance, also inhibits VEGFR2, BCR-ABL, LYN and ABL1 kinases while 2-MT 63 does not.) There is a lack of data from cell culture experiments involving this agent in the original publication. It was also shown to inhibit TIE2 autophosphorylation in vivo. However, this outcome was limited - with activity occurring at a high dose (100 mg/kg) and only transiently (positive at 3 hours but the effect was lost by 8 hours).

(last updated: 17 Mar 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

2-MT 63 is a novel TIE-2 kinase inhibitor that demonstrates unique and improved kinase selectivity compared to other inhibitors known to interact with TIE-2. The developmental focus centered on in vivo assessment, and therefore, substantial work in cells has not yet been demonstrated, though the providers adequately bridge enzymatic inhibition with demonstrated potency in a cellular autophosphorylation assay, which translates to in vivo inhibition of TIE-2 autophosphorylation. In vivo efficacy was observed by oral administration in rats at a high dose (100 mg/kg) for a short duration of 3 h. Nevertheless, 2-MT 63 represents one of the best probes one could use to further study the role of TIE-2 in angiogenesis in a selective manner.

(last updated: 29 Mar 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

2-MT 63 has a good kinase selectivity profile in enzyme assays with >30-fold selectivity (typically much greater) against the tested kinases. Importantly, the profile includes selectivity against other targets of relevance for angiogenesis (KDR, PDGFR, EPHB4). Cellular selectiivity data are not published, but the probe does have a comparable level of cellular activity (IC50=62 nM for cellular inhibition of TIE-2 phosphorylation) to enzyme inhibition (IC50=30 nM). In-vivo activity from an oral dose in mouse, albeit at a high dose of 100 mg/kg, is achieved, with inhibition of ANG-1-stimulated TIE-2 phosphorylation observed at 3 h. A time course of in-vivo activity in mouse is not presented but given the short in-vivo half life in rat (t1/2=1.6 h) a short duration of activity would not be surprising. It should be noted that the pharmacokinetic (PK) profile in mouse has not been reported (only PK data for rat are reported), despite the in-vivo PD model being in mouse.

(last updated: 15 May 2017 )