Brivanib

Protein target name:

KDR

Mechanism of action:

Inhibitor, ATP competitive

Recommended Concentration for use in cells:

up to 10 uM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:6307

Entrez gene ID:

3791

UNIPROT ID:

P35968

Target alias:

CD309, FLK1, VEGFR, VEGFR2

Probe Details

Chemical Probes Portal ID:

CPP1203

Probe alias:

BMS-540215, cpd 12

PubChem CID:

11234052

ChEMBL ID:

CHEMBL377300

SMILES string:

FC1=C(OC2=NC=NN3C2=C(C(OC[C@H](O)C)=C3)C)C=CC4=C1C=C(C)N4

InChi Key:

WCWUXEGQKLTGDX-LLVKDONJSA-N

Orthogonal probe:

Cabozantinib

Physico-chemical properties

NMR:

1H NMR (500 MHz, CDCl3) δ 7.84 (s, 1H), 7.41 (s, 1H), 7.11 (d, 1H, J = 11 Hz), 7.02 (t, 1H, J = 8.8 Hz), 6.39 (s, 1H), 4.20-4.30 (m, 1H), 3.8-4.00 (m, 2H), 2.51 (s, 3H), 2.45 (s, 3H), 1.31 (d, 3H, J = 8.2 Hz).

13C NMR (125 MHz, DMSO-d6) δ 8.36, 13.3, 20.0, 64.5, 76.36, 95.1, 100.0, 105.75, 106.66, 110.17, 115.47, 117.66, 117.8, 129.83, 136.34, 137.64, 144.13, 144.6, 146.53, 148.15, 160.71.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50,Ki

26 nM IC50,25 nM Ki

Potency assay:

Kinase Assay using [γ-33P]-ATP

Structure-activity relationship:

yes

Off target activity

Potency (off target):

IC50

Off target protein and potency:

FLK1 89 nM, FGFR1 148 nM

Probe Selectivity in Vitro:

Kinase Selectivity IC50 (nM): VEGFR-1 380, FGFR-1 148, PDGFR-β >6000, EGFR >1900, LCK >2500, PKCα >25000, JAK-3 >50000

In cell validation

On target activity in cells

Potency in cells:

IC50

40 nM (V), 276 nM (F)

Potency assay (cells):

Inhibition of cell Proliferation (VEGF (V) or FGF (F) stimulated)

In vivo validation

Organism:

Mouse, Rat

Dose:

10, 60, 90 Mg/Kg

Route of delivery:

OralIntravenous

Plasma half life:

2.7 (IV), 3.6 (PO) h

Systemic clearance:

9.3 (IV) mL/min/kg

Fraction of probe bound to plasma protein:

88 % (PO)

Cmax:

6.4 uM (R)

Primary Reference

Reference (doi):

10.1021/jm051106d 10.1007/s00280-009-1002-0

Reference (PMID):

16570908 19396600

Brivanib

Probe Availability

Probe Information

Target Details

CD309, FLK1, VEGFR, VEGFR2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Brivanib

Probe Availability

Probe Information

Target Details

CD309, FLK1, VEGFR, VEGFR2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?