Ceritinib

Protein target name:

ALK

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

MedChemExpress

TOCRIS

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

RTK

HUGO ID:

HGNC:427

Entrez gene ID:

238

UNIPROT ID:

Q9UM73

Target alias:

Anaplastic lymphoma receptor tyrosine kinase, CD246, NBLST3

Probe Details

Chemical Probes Portal ID:

CPP1205

Probe alias:

LDK378, 4MK, cpd 15, NVP-LDK378-NX

PubChem CID:

57379345

ChEMBL ID:

CHEMBL2403108

SMILES string:

CC(C)OC1=CC(C2CCNCC2)=C(C)C=C1NC3=NC=C(Cl)C(NC4=CC=CC=C4S(=O)(C(C)C)=O)=N3

InChi Key:

VERWOWGGCGHDQE-UHFFFAOYSA-N

Orthogonal probe:

CH5424802TL13-112Brigatinib

Physico-chemical properties

NMR:

1H NMR (400 MHz, DMSO-d6 + trace D2O) δ 8.32 (s, 1H), 8.27 (d, 1H), 7.88 (d, 1H), 7.67 (dd, 1H), 7.45 (dd, 1H), 7.42 (s, 1H), 6.79 (s, 1H), 4.56–4.48 (m, 1H), 3.49–3.32 (m, 3H), 3.10–2.91 (m, 3H), 2.09 (s, 3H), 1.89–1.77 (m, 4H), 1.22 (d, 6H), 1.13 (d, 6H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

0.2 nM

Potency assay:

Enzymatic Inhibition assay (LabChip mobility-shift assay)

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

4MKC

Structure-activity relationship:

yes

Off target activity

Potency (off target):

IC50

Off target protein and potency:

FLT3 60 nM, FGFR2 260 nM, RET 400 nM, FGFR3 430 nM

Potency assay (off target):

Enzymatic Inhibition assay (LabChip mobility-shift assay)

Probe Selectivity in Vitro:

Enzymatic Kinase Profile in uM: ABL 1.25, FGFR4 0.95, LYN 0.84, AKT >10, FLT3 0.06, cMET 3.17, GSK3β >10, MKNK2 2.24, Aurora 0.66, IGF-1R 0.008, PAK2 >10, BTK 3.36, InsR 0.007, PDGFRα 1.14, CDK2 3.97, JAK1 3.73, RET 0.4, CDK4 4.72, JAK2 0.61, ROCK2 1.27, EGFR 0.9, JAK3 7.92, SYK 3.05, FGFR2 0.26, cKit 1.28, STK22D 0.023, FGFR3 0.43, LCK 0.56, ZAP70 9.7

In cell validation

On target activity in cells

Potency in cells:

IC50

26 nM (BA/F3), 22.8 nM (Karpas-299)

Potency assay (cells):

Cell Proliferation Assay (Bright-Glo luciferase assay)

Off target activity in cells

Potency assay, off target (cells):

Cell Proliferation Assay (Bright-Glo luciferase assay)

Probe Selectivity in Cell:

Cellular Kinase Profile in Ba/F3 Cells (IC50, uM): Tel-ALK 40.7 ± 5.3, Tel-JAK2, 2160 ± 320, Tel-RET, 2304 ± 459, EML4-ALK 2.2 ± 0.5, Tel-KDR, 4210 ± 170, Tel-Ros 141.8 ± 22.7, Tel-FGFR3 >10000, Tel-ckit 2855 ± 215, Tel-Src 1694 ± 276, Tel-FGR 1947 ± 433, Tel-Lck 672 ± 264, Tel-TRKA 2727 ± 222 Tel-FLT3 3143 ± 933, Tel-LYN 2306 ± 552, Tel-TRKB 1829 ± 80, Tel-IGF-1R 410 ± 10, Tel-Met 1339 ± 74, Tel-WT 3250 ± 710

In vivo validation

Organism:

Mouse, Rat, Dog, Monkey

Route of delivery:

OralIntravenous

Plasma half life:

6.2 (M), 9.1 (R), 21 (D), 26 (M) h (IV) 26.6 36.8 9.2 12.8

Systemic clearance:

26.6 (M), 36.8 (R), 9.2 (D), 12.8 (M) mL/min/Kg

Cmax:

1.7 IV 0.7 PO (M), 0.77 IV 0.26 PO (R), 2.3 IV 1.9 PO (D), 2.5 IV 1.7 PO (M) uM

Tmax:

0.03 IV 7.0 PO (M), 0.03 IV 7.0 PO (R),0.03 IV 8.0 PO (D), 13 PO (M) h

Primary Reference

Reference (doi):

10.1021/jm400402q

Reference (PMID):

23742252

Ceritinib

Probe Availability

Probe Information

Target Details

Anaplastic lymphoma receptor tyrosine kinase, CD246, NBLST3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Ceritinib

Probe Availability

Probe Information

Target Details

Anaplastic lymphoma receptor tyrosine kinase, CD246, NBLST3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?