ABT-869 (Linifanib) is an ATP-competitive, multi-targeted RTK inhibitor that is completely effective against all members of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families. ABT-869 (Linifanib) showed potent antiproliferative and apoptotic properties in vitro and in animal cancer xenograft models. The kinase inhibition profile of ABT-869 is evident in cellular assays of RTK phosphorylation (IC₅₀ values of 2, 4 and 7 nM for PDGFRβ, KDR and CSF-1R, respectively) and VEGF-stimulated proliferation (0.2 nM IC₅₀ for human endothelial cells). ABT-869 is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.
 |
Source | Oral Oncol (2013). Figure 4. ABT-869 |
| Method | Analysis of apoptosis | |
| Cell Lines | SCC-22A and B cells | |
| Concentrations | 20 μM | |
| Incubation Time | 12 h | |
| Results | ABT-869 treatment increased the apoptotic population by 4.61 and 3.11-fold and by 9.15 and 5.33-fold increase in combination in SCC-22A and B cells, as compared to untreated and radiation alone groups respectively |
 |
Source | Oral Oncol (2013). Figure 3. ABT-869 |
| Method | Cell cycle analysis | |
| Cell Lines | SCC-22A and B cells | |
| Concentrations | 20 μM | |
| Incubation Time | 12 h | |
| Results | Compared to control group, we observed significant accumulation in G2/M phase in SCC-22A (42.2% versus 23.4% in control) and in SCC-22B cells (24.6% versus 17% in control), after ABT-869 treatment, indicating that a higher number of cells were blocked in a more radiosensitive phase of the cell cycle. |
| Cell Experiment | |
|---|---|
| Cell lines | HUAEC cells |
| Preparation method | Cell Proliferation. HUAEC were plated into 96-well plates at 2,500 per well and incubated with serum-free medium for 24 hours. Drug and VEGF (final, 10 ng/mL) were added and incubated for 72 hours in serum-free medium. For carcinoma cell lines, 2,500 per well were plated overnight in full growth medium. Drug was added to the cells in full growth medium and incubated for 72 hours. For leukemia cells, generally 50,000 per well were plated in full growth medium, drug added, and incubated for 72 hours. The effects on proliferation were determined by addition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37°C in a CO2 incubator, and analysis in a fluorescence plate reader (544 nm, excitation: 590 nm, emission). For VEGF-stimulated growth, percent inhibition of proliferation was determined using the difference between VEGF-stimulated cells and unstimulated cells as the control, and IC50 values were determined by nonlinear regression analysis of the concentration response data. |
| Concentrations | 0~1µM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | HT1080 (A), H526 (B), and MX-1 (C) human tumor cells xenograft models |
| Formulation | 2% ethanol, 5% Tween 80, 20% PEG400, 73% saline |
| Dosages | 1.5, 5 or 15mg/kg bid |
| Administration | orally |
| Molecular Weight | 375.41 |
| Formula | C21H18FN5O |
| CAS Number | 796967-16-3 |
| Solubility (25°C) | DMSO ≥70 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related VEGFR/PDGFR Products |
|---|
| Isolinderalactone
Isolinderalactone suppresses human glioblastoma growth and angiogenic activity through the inhibition of VEGFR2 activation in endothelial cells. Isolinderalactone suppressed the expression of B-cell lymphoma 2 (BCL-2), as well as of survivin and X-linked inhibitor of apoptosis protein (XIAP). |
| Oglufanide
Oglufanide (H-Glu-Trp-OH) is a dipeptide immunomodulator isolated from calf thymus. |
| KLTWQELYQLKYKGI
KLTWQELYQLKYKGI (QK) is a VEGF mimicking peptide, binds to the VEGF receptors and competes with VEGF. |
| Protein LMWP
Protein LMWP is a cell-penetrating peptide with vascular endothelial growth factor (VEGF) inhibitory activity. |
| CBO-P11
CBO-P11 specifically binds to receptor of VEGFR-2 and is used as targeting ligand for tumor angiogenesis. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
