Multiple tyrosine kinase inhibitor

Jonas JC, Plant TD, Gilon P, Detimary P, Nenquin M and Henquin JC. 1995. Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. Br J Pharmacol 114(4) 872-880. 

Rosen L, Hannah A, Rosen P, et al. Phase I dose-escalating trial of oral SU006668, a novel multiple receptor tyrosine kinase inhibitor in patients with selected advanced malignancies. Proc Am Soc Clin Oncol 2000 19 182 (abst). 

Shah NP, Nieoll JM, Nagar B et al. Multiple BCR-ABL kinase domain mutations eonfer polyelonal resistanee to the tyrosine kinase inhibitor imatinib (ST1571) in ehronie phase and blast erisis ehronie myeloid leukemia. Cancer Ce//2002 2 117-125. 

Protein kinases can be classified according to the amino acid residue that is phosphorylated in the cellular process. Consequently, there are tyrosine-specific kinases and serine/threonine kinases. Tyrosine kinases are a family of tightly regulated enzymes, and the aberrant activation of various members of this family is one of the hallmarks of cancer. Tyrosine phosphorylation has been linked to multiple cell growth and differentiation pathways. Imatinib mesylate (1) is a tyrosine kinase inhibitor (TKI). An important characteristic of imatinib mesylate (1) is that it is an ATP-competitive inhibitor. It binds at the ATP binding site and blocks ATP binding thereby inhibiting kinase activities. 

Semaxanib (SU-5416) was discovered in Sugen (owned by Pharmacia at the time, now Pfizer) as the lead compound in a series of small-molecule inhibitors of the multiple tyrosine kinase receptor for the potential treatment of cancer. In February 2002, Pharmacia made the decision to discontinue the drug based on interim results from phase III trials involving colorectal cancer patients. 

In 2008, Fagnou [124] achieved multiple C-H arylations of 1,3-azoles such as thiazoles and imidazoles by converting them into the corresponding azole N-oxides. Subsequently, they accomplished the synthesis of Tie2 tyrosine kinase inhibitor 87... 

Systobc dysfunction and heart failure are some of the most common cardiovascular side effects of tyrosine kinase inhibitors. This may occur because the pathways that are involved in the survival of cancer cells also appear to be involved in the survival of some normal cells (Chen et al. 2011). The tyrosine kinase inhibitors include molecules that target mie or a few tyrosine kinases to those that target multiple tyrosine kinases. Although targeting multiple kinases may add efficacy, this also increases the likelihood for inducing toxicities. The toxicities that are observed appear to be on-target, i.e., directly related to the type of tyrosine kinase that is inhibited. 

HV, healthy volunteers M, males F, females XO, crossover SD, single dose MD, multiple dose T, therapeutic dose ST, supratherapeutic dose P, placebo M, moxifloxacin, single oral dose of 400 mg nested XO, nested crossover comparison for moxifloxacin lacebo within a parallel group study T + keto, therapeutic dose concomitant with ketoconazole. TKI, tyrosine kinase inhibitor, Cl, confidence interval LB, lower bound. Negative upper bound of Cl < 10 ms for doses studied... 

N -(3-bromophenyl)-7-(substitutedbenzyl)-7H-pyrrolo[2,3-of pyrimidine-2,4-diamines as novel potent multiple receptor tyrosine kinase inhibitors... 

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