ABT-869 (Linifanib) is an aminobenzopyrazole-based, orally available, ATP-competitive receptor tyrosine kinase inhibitor with IC50 potency against KDR, FLT1, CSF-1R, FLT3, and PDGFRb of 4 nM, 3 nM, 3 nM, 4 nM, and 66 nM, respectively. It is highly selective (> 1uM) against unrelated tyrosine kinases and serine/threonine kinases. [1] In cellular assays, ABT-689 exhibited potency against ligand-induced PDGFRbeat, KIT, and CSF-1R phosphorylation, with IC50s of 2, 31, and 10 nM, respectively.In vivo, ABT-869 is orally effective in a wide range of human xenograft models, including MV4-11, HT1080, H526, DLD-1, A431, MX-1, MDA-231, MDA-435LM, and glioma 9L. [2] ABT-869 displays antiproliferative and apoptotic effects on cancer cells dependent on mutant kinases, such as FLT3. Consequently, ABT-869 is in clinical studies for the treatment of acute myeloid leukemia (AML). [3, 4] ABT-689 has been shown to induce apoptosis through an AKT and GSK-3beta-dependent pathway, thus suggesting that combination therapies with GSK-3beta inhibitors may be a promising approach to AML treatment. [3]
Technical information:
| Chemical Formula: | C21H18FN5O | |
| CAS #: | 796967-16-3 | |
| Molecular Weight: | 375.41 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | 1-(4-(3-amino-1H-indazol-4-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | ABT-869, ABT 869, ABT869, AL-39324, AL39324, Linifanib |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Albert et al., Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer Ther. 2006, 5, 995-1006. Pubmed ID:16648571 |
| 2. | Zhou et al., ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. J. Hematol. Oncol. 2009, 2, 33-45. Pubmed ID:19642998 |
| 3. | Hernandez-Davies et al., The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces apoptosis through an Akt and glycogen synthase kinase 3?-dependent pathway. Mol. Cancer Ther. 2011, 10, 949-959. Pubmed ID:21471285 |
| 4. | Shankar et al., ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia. Blood, 2007, 109, 3400-3408. Pubmed ID:19642998 |
Other Information:
Product Specification (pdf) MSDS (pdf) Certificate of Analysis is available upon request.
