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Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.
TLDR
OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing. Expand
A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I
TLDR
PQIP represents a potent and selective IGF-IR kinase inhibitor that is especially efficacious in an IGF-II–driven human tumor model and correlated with the degree and duration of inhibition of tumor IGF- IR phosphorylation in vivo by this compound. Expand
Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors.
TLDR
Resistance to inhibition of MEK, mTOR, and EGFR is associated with enhanced IGF-IR-directed Akt signaling, where all affect feedback loops converging at the level of IRS-1. Expand
The RON Receptor Tyrosine Kinase Promotes Metastasis by Triggering MBD4-Dependent DNA Methylation Reprogramming
TLDR
Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome and inhibition of Ron kinase activity with a pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo. Expand
Small‐molecule inhibition and activation‐loop trans‐phosphorylation of the IGF1 receptor
The insulin‐like growth factor‐1 receptor (IGF1R) is a receptor tyrosine kinase (RTK) that has a critical role in mitogenic signalling during embryogenesis and an antiapoptotic role in the survivalExpand
The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis.
A complex of RON(M1254T) with AMP-PNP and Mg(2+) reveals a substratelike positioning of Tyr1238 as well as likely catalysis-competent placement of the AMP-PNP and Mg(2+) components and indicates aExpand
Small molecule inhibitors of the IGF-1R/IR axis for the treatment of cancer
TLDR
The clinical success for IGF-1R/IR inhibitors may ultimately be dependent upon the ability to correctly administer these agents to the right niche patient subpopulation using single agent therapy, when appropriate, or using the right combination therapy. Expand
1,3-Disubstituted-imidazo[1,5-a]pyrazines as insulin-like growth-factor-I receptor (IGF-IR) inhibitors.
A series of novel 8-amino-1,3-disubstituted-imidazo[1,5-a]pyrazines was designed and synthesized as IGF-IR inhibitors.
Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: optimization of kinase selectivity and pharmacokinetics.
TLDR
The intersection of insights from molecular modeling, computational prediction of metabolic sites, and in vitro metabolite identification studies resulted in a simple and unique solution to both kinase selectivity and pharmacokinetic optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1. Expand
A highly effective one-pot synthesis of quinolines from o-nitroarylcarbaldehydes.
TLDR
A highly effective one-pot Friedländer quinoline synthesis using inexpensive reagents has been developed and can be applied to mono- or di-substituted quinolines in high yields. Expand
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