1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. PDGFR
    VEGFR
    Autophagy
    FLT3

Linifanib (Synonyms: ABT-869; AL-39324)

Cat. No.: HY-50751 Purity: 99.80%
Data Sheet SDS Handling Instructions

Linifanib (ABT-869) is a multi-targeted inhibitor of VEGF and PDGFR receptor family with IC50s of 3, 4, 66, 4 nM for KDR, Flt-1, PDGFRβ and FLT3.

For research use only. We do not sell to patients.
Linifanib Chemical Structure

Linifanib Chemical Structure

CAS No. : 796967-16-3

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $66 In-stock
5 mg $60 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $440 In-stock
200 mg $740 In-stock
500 mg $1400 In-stock
1 g   Get quote  
5 g   Get quote  

* Please select Quantity before adding items.

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Linifanib (ABT-869) is a multi-targeted inhibitor of VEGF and PDGFR receptor family with IC50s of 3, 4, 66, 4 nM for KDR, Flt-1, PDGFRβ and FLT3.

IC50 & Target

IC50: 3 nM (KDR), 4 nM (Flt-1), 66 nM (PDGFRβ), 4 nM (FLT3)[1]

In Vitro

Linifanib exhibits IC50 values that range from 4 nM (KDR) to 190 nM (FLT4) for members of the VEGF and PDGF receptor families. Linifanib is also active against TIE2 and, to a lesser extent, RET, but is much less active (IC50>10 μM) against other nonrelated tyrosine kinases, such as steroid receptor coactivator and epidermal growth factor receptor. Phosphorylation of KDR induced by VEGF is inhibited by Linifanib with an IC50 of 4 nM in 3T3 murine fibroblasts engineered to express human KDR. A similar potency for inhibition of receptor autophosphorylation is seen with Linifanib when HUAECs are used as the target cell. Linifanib inhibits VEGF-stimulated phosphorylation of KDR completely at 10 nM and by 70% at 3 nM (IC50=2 nM)[1].

In Vivo

Linifanib is effective orally in the mechanism-based murine models of VEGF-induced uterine edema (ED50=0.5 mg/kg) and corneal angiogenesis (>50% inhibition, 15 mg/kg). ABT-869 exhibits efficacy in human fibrosarcoma and breast, colon, and small cell lung carcinoma xenograft models (ED50=1.5-5 mg/kg, twice daily) and is also effective (>50% inhibition) in orthotopic breast and glioma models. Reduction in tumor size and tumor regression is observed in epidermoid carcinoma and leukemia xenograft models, respectively[1].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.6638 mL 13.3191 mL 26.6383 mL
5 mM 0.5328 mL 2.6638 mL 5.3277 mL
10 mM 0.2664 mL 1.3319 mL 2.6638 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

For tyrosine kinase assays, a biotinylated peptide substrate containing a single tyrosine is used with 1 mM ATP, an Eu-cryptate-labeled anti-phosphotyrosine antibody (PT66), and Strepavidin-APC in a homogeneous timeresolved fluorescence assay. Serine/threonine kinases are assayed using 5 μM ATP, [33P]ATP, and a biotinylated peptide substrate with peptide capture and incorporation of 33P determined using a SA-Flashplate. Linifanib is assayed at multiple concentrations prepared by serial dilution of a DMSO stock solution of the compound. The concentration resulting in 50% inhibition of activity is calculated using nonlinear regression analysis of the concentration response data[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

HUAEC are plated into 96-well plates at 2,500 per well and incubated with serum-free medium for 24 hours. Linifanib and VEGF(final, 10 ng/mL) are added and incubated for 72 hours in serum-free medium. For carcinoma cell lines, 2,500 per well are plated overnight in full growth medium. Linifanib is added to the cells in full growth medium and incubated for 72 hours. For leukemia cells, generally 50,000 per well are plated in full growth medium, drug added, and incubated for 72 hours. The effects on proliferation are determined by addition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37jC in a CO2 incubator, and analysis in a fluorescence plate reader[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mouse: Tumor-bearing animals are divided into groups (n=10), and administration of vehicle (2% ethanol, 5% Tween 80, 20% PEG400, 73% saline) or inhibitor (Linifanib) at the indicted dose is initiated. Tumor growth in the flank is assessed by measuring tumor size with calipers and calculating size. Tumor volume for the orthotopic glioma model is determined using magnetic resonance imaging[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

375.4

Formula

C₂₁H₁₈FN₅O

CAS No.

796967-16-3

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO ≥72mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.80%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Linifanib
Cat. No.:
HY-50751
Quantity: