TIVOZANIB

TIVOZANIB : Inhibitor of VEGFR1-3

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe TIVOZANIB is in the process of SERP review.

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Information

FLT1
KDR
FLT4

Inhibitor

up to 1 uM
Reviewer recommended concentration: 10 nM and no more than 50 nM.

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P17948

Target Class: Kinase

Target SubClass: Tyrosine kinase

Potency: IC50

Potency Value: 30.6 nM

Potency Assay: activity based assay

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

Target aliases:

Vascular endothelial growth factor receptor 1, VEG ...

DOI Reference: 10.1158/0008-5472.CAN-05-4290

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): Activity-based assay at 1 µM ATP (ProQinase). KRN951 also inhibited c-Kit and PDGFR-β phosphorylation with IC50 values ∼10-fold higher than for VEGFR-2 and EphB2, PDGFR-α, PDGFR-β, c-Kit, and Tie2 tyrosine kinases (IC50 = 24, 40, 49, 78, and 78 nmol/L, respectively). The KRN951 activity level against the phosphorylation of FGFR-1, Flt3, c-Met EGFR, and IGF-IR was considerably lower

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Tivozanib is a clinically approved VEGF kinase inhibitor with established efficacy and suitable safety in renal cell carcinoma. I has therefore been extensively profiled in vivo across multiple species and many cancer cell models, providing a rich source of guidance for appropriate dosing strategies and regimens. Nevertheless, as a chemical probe used to deconvolute pathway biology, its use is limited by a lack of selectivity against other tyrosine kinases. At 1uM >90% inhibition of >25 other tyrosine kinases has been reported (doi.org/10.1007/s00280-023-04534-7).

(last updated: 21 Aug 2023 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Cellular IC50s are cited as being sub-nanomolar to single-digit-nanomolar. Given that cited biochemical selectivity over other RTK targets is only 10-100-fold, cellular concentrations should be kept as low as possible to maintain likelihood of on-target mechanism, 1 uM is too high.

(last updated: 15 Feb 2024 )