ZIMLOVISERTIB

ZIMLOVISERTIB : Inhibitor of IRAK4

Structure

SERP Rating

In Cells

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In Model Organisms

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Information

IRAK4

Inhibitor

up to 100 nM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9NWZ3

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 0.2 ± 0.1 nM

Potency Assay: DELFIA assay using activated full-length IRAK4 protein in the presence of 600 μM ATP (i.e., ATP Km) and assessing phosphorylation of a peptide substrate

PDB ID for probe-target interaction (3D structure): 5UIU

Target aliases:

Interleukin-1 receptor-associated kinase 4, IRAK4, ...

DOI Reference: 10.1021/acs.jmedchem.7b00231

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): The kinome selectivity profile of ZIMLOVISERTIB was assessed in a panel of 278 kinases (Invitrogen) at 200 nM inhibitor concentration using the ATP Km for each kinase. Approximately 100% inhibition was observed for IRAK4, while greater than 70% inhibition was observed for the following kinases, in order of potency: IRAK1, MNK2, LRRK2, CLK4, and CK1γ1. ZIMLOVISERTIB was evaluated in a wide ligand profile screen (CEREP) at 10 μM. ZIMLOVISERTIB demonstrated activity against VEGFR2 (KDR) kinase (activity defined by a response greater than 50% of a maximal response). A follow-up concentration-response curve was generated, and the VEGFR2 IC50 value was determined to be 5330 nM.

Potency assay, off target (cells): KiNativ kinome screen (ActivX) in THP1 cell lysates at concentrations of 10, 50, 200, 1000, and 5000 nM to assess kinase selectivity under more physiological conditions. Of the approximately 270 unique kinases profiled, only these kinases other than IRAK4 displayed greater than 50% inhibition at 200 nM: CK1γ2, IRAK3/M, PIPK2C, and CK1δ/ε. ZIMLOVISERTIB was assessed in a whole-cell functional VEGF2R assay (PAE-KDR cell line). No activity was observed at concentrations up to and including 30 μM.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

In Model Organisms

SERP+ Comments:

ZIMLOVISERTIB showed promising in vivo results in monkeys, dogs and rats.

(last updated: 22 Mar 2023 )