journal={Drugs in R\&D},
  pages={111 - 122}
  • Published 2010
  • Medicine
  • Drugs in R&D
Linifanib (A 741439; A-741439; A741439; ABT-869; ABT869; RG3635) is an orally active multi-targeted receptor tyrosine kinase inhibitor for the treatment of various cancers. It was being developed by Roche but development has now reverted to Abbott. The compound is designed to inhibit vascular endothelial growth factor and platelet-derived growth factor receptors. It is in phase III development for liver cancer and phase II development for non-small cell lung cancer, breast cancer, and… Expand
4 Citations
VEGF and FGF-2: Promising targets for the treatment of respiratory disorders.
VEGF and FGF-2 are the strongest activators of angiogenesis which stimulate migration and proliferation of endothelial cells in existing vessels to generate and stabilize new blood vessels and their role as anti-angiogenetic agents in lung disorders is highlighted. Expand
Feature selection strategies for drug sensitivity prediction
Based on GDSC drug data, it is found that feature selection driven by prior knowledge tends to yield better results for drugs targeting specific genes and pathways, while models with the genome-wide features perform better for drugs affecting general mechanisms such as metabolism and DNA replication. Expand
Feature selection strategies for drug sensitivity prediction
Standard, data-driven feature selection approaches to feature selection driven by prior knowledge of drug targets, target pathways, and gene expression signatures are compared, finding small feature sets selected using prior knowledge are more predictive for drugs targeting specific genes and pathways, while models with wider feature sets perform better for drugs affecting general cellular mechanisms. Expand


Abstract B14: The broad spectrum antitumor efficacy and tolerability of the RTK inhibitor, linifanib (ABT‐869) alone and in combination with various cytotoxic therapies
The ability of linifanib to inhibit tumor growth in known hypervascular/angiogenic tumors suggests on‐mechanism activity as well as demonstrating the ability to be used as combination treatment regimen without excessive impact on tolerability is of great interest to increase clinical efficacy and positively impact patient outcomes. Expand
Linifanib phase II trial in patients with advanced hepatocellular carcinoma (HCC).
Linifanib, a novel potent and selective inhibitor of the VEGF and PDGF platelet-derived growth factor families of RTKs, is designed to inhibit angiogenesis, tumor growth, and metastasis. Expand
Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor
In tumor growth studies, ABT-869 exhibits efficacy in human fibrosarcoma and breast, colon, and small cell lung carcinoma xenograft models and is also effective in orthotopic breast and glioma models. Expand
Extended linifanib therapy in patients with advanced solid tumors in a phase I trial.
Linifanib (ABT-869) is an orally bioavailable, potent, selective VEGF and PDGF RTK inhibitor that was observed in a phase I trial of patients with advanced solid tumors including PR in non-small cell lung cancer and colorectal cancer and prolonged SD in many pts (JCO 2009;27:4718-26). Expand
Abstract A105: Phase 2 trials of linifanib (ABT‐869) in advanced hepatocellular, renal cell and non‐small cell lung cancer: Associations of response by CT or DCE‐MRI with patient outcome
CT tumor volume reduction and CT response were associated with improved OS and PFS, and greater baseline Ktrans was associated withImproved OS but not PFS. Expand
Abstract B53: Assessment of the effect of food on the oral bioavailability and assessment of diurnal variation in the pharmacokinetics of linifanib
Preliminary results show that linifanib exposures may be influenced by food and time of dosing. Expand
Identification of Core Gene Signature Associated with Synergism Between ABT-869, a FLT3 Inhibitor and SAHA, a HDAC Inhibitor in AML with FLT3-ITD Mutation.
Cell proliferation and apoptosis assays revealed that combining ABT-869 with SAHA led to synergistic killing of AML cells with FLT3 mutations in conventional cell culture and human stromal cell coculture models. Expand
ABT-869 a novel multi-targeted receptor tyrosine kinase inhibitor: characterization of FLT3 phosphorylation in a model of acute myelogenous leukemia
In vivo ABT-869 demonstrated pronounced regression of established MV-4-11 xenograft tumors and inhibition of FLT3 phosphorylation in the MV- 4-11 tumors grown in the flank of SCID mice, providing some insight into the mechanism of action of ABT -869 that could be transferred to the clinical setting as a biomarker of ABTs activity. Expand
The Multi-Targeted Receptor Tyrosine Kinase Inhibitor, ABT-869, Induces Apoptosis of AML Cells Both In Vitro and In Vivo.
The results suggest that ABT-869 is not toxic to normal bone marrow progenitor cells at concentrations that are effective against AML cells, and provide rationale for the prevention of relapse in AML patients. Expand
Phase II trial of linifanib in patients with advanced renal cell cancer (RCC) after sunitinib failure.
This study investigated the efficacy and safety of linifanib in patients with RCC following sunitinib failure, and overall response rate (ORR) by central imaging. Expand