- Rational Design, Optimization, and Biological Evaluation of Novel MEK4 Inhibitors against Pancreatic Adenocarcinoma
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Growth, division, and development of healthy cells relies on efficient response to environmental survival cues. The conserved mitogen-activated protein kinase (MAPK) family of pathways interface extracellular stimuli to intracellular processes for this purpose. Within these pathways, the MEK family has been identified as a target of interest due to its clinical relevance. Particularly, MEK4 has drawn recent attention for its indications in pancreatic and prostate cancers. Here, we report two potent MEK4 inhibitors demonstrating significant reduction of phospho-JNK and antiproliferative properties against pancreatic cancer cell lines. Furthermore, molecular inhibition of MEK4 pathway activates the MEK1/2 pathway, with the combination of MEK1/2 and MEK4 inhibitors demonstrating synergistic effects against pancreatic cancer cells. Our inhibitors provided insight into the crosstalk between MAPK pathways and new tools for elucidating the roles of MEK4 in disease states, findings which will pave the way for better understanding of the MAPK pathways and development of additional probes.
- Kwong, Ada J.,Munshi, Hidayatullah G.,Oelschlager, Hannah E.,Pham, Thao N. D.,Scheidt, Karl A.
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supporting information
p. 1559 - 1567
(2021/10/04)
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- FLUORINE-SUBSTITUTED INDAZOLE COMPOUNDS AND USES THEREOF
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Fluorine-substituted indazole compounds, pharmaceutical compositions containing these compounds and uses thereof. The compounds and pharmaceutical compositions can be used as soluble guanylate cyclase simulators.
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Paragraph 00316
(2018/11/10)
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- Α 7 as intranuclear hydroxynicotinic acetylcholine receptor quinuclidines compd.
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PROBLEM TO BE SOLVED: To provide ligands for the nicotinic α-7 receptor used for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.SOLUTION: The disclosure provides compounds of the specified formula I, including their salts, and compositions and methods using the compounds.
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Paragraph 0264; 0265
(2018/10/03)
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- Compounds as syk kinase inhibitors
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The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by inhibition of Syk kinase.
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Paragraph 0300; 0301
(2013/03/26)
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- QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic 7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.
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Page/Page column 133
(2011/05/11)
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- Two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles
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A general two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles involving a palladium-catalyzed arylation of benzophenone hydrazone followed by an acidic deprotection/cyclization sequence is described. This procedure offers a general and efficient alternative to the typical S NAr reaction of hydrazine with o-fluorobenzonitriles.
- Lefebvre, Valerie,Cailly, Thomas,Fabis, Frederic,Rault, Sylvain
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supporting information; experimental part
p. 2730 - 2732
(2010/07/08)
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- PYRIMIDOPYRIMIDOINDAZOLE DERIVATIVE
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The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a):; R1 means a -(C=O)aOb(C1-C6)alkyl group, a -(C=O)aOb(C2-C6)alkenyl group, a -(C=O)aOb(C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R2 and R3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a -(C=O)aOb(C1-C6)alkyl group or a group of -(C=O)aN(R1e)R2e; R4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.
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Page/Page column 89
(2010/09/17)
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- QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.
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Page/Page column 82-83
(2009/10/31)
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- INDAZOLE DERIVATIVES
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The invention is concerned with novel indazole derivatives of formula (I) wherein R1, R2, R3, R4, R5, R6, X and Y are as defined in the description and in the claims, as well as physiologic
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Page/Page column 16
(2008/06/13)
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