655225-01-7Relevant academic research and scientific papers
Lipid compound and composition thereof
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Paragraph 0209-0216, (2021/07/31)
The invention relates to a lipid compound and a composition thereof, a lipid nanoparticle containing the composition, a preparation method of the composition and application of the composition in drug delivery.
METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS
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, (2022/01/04)
The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.
Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: High-throughput virtual screening, synthesis and biological validation
Xiang, Sichuan,Huang, Ding,He, Qiaolin,Li, Jie,Tam, Kin Yip,Zhang, Shao-Lin,He, Yun
, (2020/07/21)
Most cancer cells feature an altered glucose metabolism from oxidative phosphorylation to cytoplasmic glycolysis. Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing of anticancer therapeutics. Herein, we describe the first discovery of series novel dual inhibitors targeting PDKs and LDHA. We identified 6 hits from a library database containing 485465 compounds through a high-throughput virtual screening assay. Hit-to-lead optimization enabled us to discover two compounds, namely 20e and 20k, which inhibited PDKs with IC50 values of 0.8, and 1.6 μM, respectively, and inhibited LDHA with IC50 values of 0.15 and 0.7 μM, respectively. Meanwhile, the two compounds reduced A549 cell proliferation with EC50 values of 13.2, and 15.7 μM. Furthermore, 20e and 20k decreased the lactate formation, and increased oxygen consumption, suggesting the two compounds modulated the glucose metabolic pathways in cancer cells.
Double-target inhibitor targeting pyruvate dehydrogenase kinase and human lactate dehydrogenase A
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, (2020/09/30)
The invention relates to compounds represented by formulas (5) and (11) or pharmaceutically acceptable salts thereof, which can simultaneously inhibit pyruvate dehydrogenase kinase and lactate dehydrogenase, and are useful, but not limited to, in the treatment of cancer diseases, wherein R1 is independently selected from phenyl, pyrimidinyl, pyridyl, heterocyclic group, alkenyl, halogen substituted alkyl and benzhydryl, and phenyl is optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, alkyl, alkoxy, nitro and trifluoromethyl. R2 is independently selected from phenyl, pyridyl, dichloroacetyl and furyl, wherein phenyl is optionally substituted by one or more substituents independently selected from fluorine, chlorine, bromine, alkyl, alkoxy, nitro and trifluoromethyl.
C26-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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, (2019/11/21)
The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.
C40-, C28-, AND C-32-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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, (2019/11/19)
The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.
COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
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Paragraph 0367, (2016/10/27)
PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
COVALENT INHIBITORS OF KRAS G12C
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Paragraph 0575, (2014/09/30)
Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.
QUINAZOLINE DERIVATIVES WITH HSP90 INHIBITORY ACTIVITY
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Page/Page column 37; 38, (2013/05/22)
Compounds of general formula (I): or a stereoisomer, tautomer, polymorph, hydrate, solvate, or a pharmaceutically acceptable salt thereof, wherein R is as defined herein, are useful for the treatment of diseases and conditions which are mediated by excessive or inappropriate Hsp90 activity such as proliferative diseases, e.g. cancers, viral and fungal infections, neurodegenerative or inflammatory diseases or conditions. The invention also relates to the preparation of these compounds as well as to pharmaceutical compositions comprising them.
NOVEL COMPOUNDS AS CALCIUM CHANNEL BLOCKERS
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Page/Page column 98, (2010/04/27)
The present application relates to calcium channel inhibitors containing compounds of formula (I) wherein Ar1, Ar2, L1, L2, n, R1, R4, X and Y are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
