Rociletinib

Protein target name:

EGFR

Mechanism of action:

Covalent InhibitorMutant Specific

Recommended Concentration for use in cells:

100 - 1000 nM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

RTK

HUGO ID:

HGNC:3236

Entrez gene ID:

1956

UNIPROT ID:

P00533

Target alias:

ERBB, ERBB1, HER1, NISBD2, PIG61, mENA

Probe Details

Chemical Probes Portal ID:

CPP1224

Probe alias:

CO-1686; AVL-301; CNX-419; 8JC

PubChem CID:

57335384

ChEMBL ID:

CHEMBL3545308

SMILES string:

CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC(=CC=C4)NC(=O)C=C)C(F)(F)F)OC

InChi Key:

HUFOZJXAKZVRNJ-UHFFFAOYSA-N

Orthogonal probe:

WZ4002

Physico-chemical properties

NMR:

1H-NMR (DMSO-d6, 400 MHz) δ 10.2 (S, 1 H), 8.2 (br, 1 H), 8.30 (S, 1 H), 7.73 (br, 1 H), 7.52 (d, J = 7.8 Hz, 1 H), 7.45 (d, J = 7.8 Hz, 1 H), 7.26 (J = 8.2 Hz, 1 H), 7.14 (be, 1 H), 6.60 (S, 1 H), 6.42 (dd, J = 11.4, 16.9 3 Hz, 1 H), 6.24 (d, J = 16.9 Hz, 1 H), 5.75 (d, J = 11.4 Hz, 1 H), 3.76 (S, 3 H), 3.04 (br, 4 H), 2.04 (S, 3 H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

21.5 nM L858R/T790M, 303.3 nM WT

Potency assay:

Continuous Omnia® Read Assay

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

5XDL, 5XDK

Off target activity

Probe Selectivity in Vitro:

Rociletinib selectivity was tested against 434 kinases in duplicate at a concentration of 0.1μM and ATP concentration of 10μM. Rociletinib inhibited 13 kinases greater than 50% with FTL3 inhibition at 94%, although IC50-apparent was only 223 nM (vs 0.5 EGFR L858R/T790M)

In cell validation

On target activity in cells

Potency in cells:

IC50

62-187 nM

Potency assay (cells):

Immunoblotting pEGFR and total EGFR, Cell proliferation assays

In vivo validation

Organism:

Mouse

Dose:

3-100 mg/Kg

Route of delivery:

Oral

Plasma half life:

2.6 h

Primary Reference

Reference (doi):

10.1158/2159-8290.CD-13-0314 10.1158/1535-7163.MCT-13-0966

Reference (PMID):

24065731 24723450

Rociletinib

Probe Availability

Probe Information

Target Details

ERBB, ERBB1, HER1, NISBD2, PIG61, mENA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Rociletinib

Probe Availability

Probe Information

Target Details

ERBB, ERBB1, HER1, NISBD2, PIG61, mENA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?