CAS: 1037624-75-1; (S)-1-(6,7-Dihydro-5H-Benzo[6,7]Cyclohepta[1,2-C]Pyridazin-3-yl)-N3-(7-(Pyrrolidin-1-yl)-6,7,8,9-Tetrahydro-5H-Benzo[7]Annulen-2-yl)-1H-1,2,4-Triazole-3,5-Diamine

上下游产品

phenyl (S)-N'-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)carbamimidate 3-hydrazino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine α,α'-dibromo-o-xylene cycloheptene-2,4-dicarboxylatedimethyl 1,2,4,5-tetrahydro-3-oxobenz°Cycloheptene-2,4-dicarboxylate

📜4,5,6,7-Tetrahydrobenzo[6,7]Cyclohepta[1,2-C]Pyridazin-3-One置于肼,三氯氧磷体系中,用 异丙醇 用作溶剂,化学反应生成1-(6,7-二氢-5H-苯并[6,7]环庚烷并[1,2-C]哒嗪-3-基)-N3-[(7S)-6,7,8,9-四氢-7-(1-吡咯烷基)-5H-苯并环庚烯-2-基]-1H-1,2,4-三唑-3,5-二胺
参考文献:Bemcentinib. Tyrosine-Protein Kinase Receptor Ufo (Axl) Inhibitor,Treatment Of Cancer
标题:Bemcentinib. Tyrosine-Protein Kinase Receptor Ufo (Axl) Inhibitor,Treatment Of Cancer
摘要:Increased Expression Of Axl Has Been Reported In Various Cancers Including Colon,Esophageal,Thyroid,Breast,Lung,Liver And Astrocytoma-Glioblastoma. Cancer Resistance To Tyrosine Kinase Inhibitors And Other Chemotherapeutics Has Been Correlated With Aberrant Expression Of Axl. These Findings Support The Development Of Axl Inhibitors In Combination With Targeted Agents To Tackle Acquired Resistance And High Axl Levels. Bemcentinib (Bgb-324,R-428) Is An Oral,Potent And Selective Small-Molecule Inhibitor Of Axl Kinase In Vitro With Ic50 Values In The Low Nanomolar Range. In Preclinical Studies,Bemcentinib Demonstrated Efficacy Across Multiple Cancer Models. It Has Also Shown A Favorable Safety Profile In Clinical Studies In Cancer Patients,And Encouraging Activity In Acute Myeloid Leukemia (Aml) And Non-Small Cell Lung Cancer (Nsclc). Currently,There Are Phase Ii Studies With Bemcentinib Ongoing In Advanced Nsclc,Triple-Negative Breast Cancer,Aml And Myelodysplastic Syndromes,And Metastatic Melanoma. Orphan Drug Designation Was Granted By The U.S. Food And Drug Administration For The Treatment Of Aml.
Doi:10.1358/dof.2018.043.09.2808543

专利信息

专利号:US-2021072244-A1
优先权日:2018-01-04
标 题:Methods and compositions for treating melanoma resistant
发明人：BERTOLOTTO CORINE; OHANNA MICKAËL; BALLOTTI ROBERT
权利人:INST NAT SANTE RECH MED; UNIV COTE D'AZUR
摘要:The present invention relates to a method for treating a subject suffering from melanoma resistant by administering to said subject an inhibitor of NAMPT. Using a global metabolic profiling, inventors have showed that in addition to glycolysis, the BRAF inhibitor, PLX4032, promoted a complex metabolic rewiring of melanoma cells, including protein catabolism and fatty acid synthesis. Importantly, they observed that PLX4032 reduced the levels of nicotinamide adenine dinucleotide (NAD+), an important redox co-factor in numerous metabolic processes, including glycolysis, tricarboxylic acid cycle (TCA) cycle, glutamate metabolism and fatty acid betaoxidation. Pharmacological or genetic inhibition of NAMPT impaired melanoma cell growth, whereas the overexpression of NAMPT dampened the antiproliferative effect of PLX4032. In vivo, the inhibition of NAMPT also prevented the xenograft development of PLX4032-sensitive and -resistant melanoma cells, identifying NAMPT as a potential target for BRAFi-resistant melanomas.

专利号:WO-2024231384-A1
优先权日:2023-05-10
标题:Compositions for treating senescence related disease
发明人：PENDE MARIO; FUMAGALLI STEFANO
权利人:INST NAT SANTE RECH MED; CENTRE NAT RECH SCIENT; UNIV PARIS CITE
摘要:Inventors have identified glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) metabolism as potent regulators of the senescent program at the nexus of TAG and PL metabolism. They show that Glycerol kinase (GK) and Phosphate Cytidylyltransferase 2 Ethanolamine (Pcyt2) activities, which catalyse regulatory steps in TAG and PL synthesis impact G3P and PEtn levels in a homeostatic fashion controlling the senescence program. Finally, they provide evidence that pharmacological inhibitors of GK activity act senomorphic, thus suggesting a novel therapeutic target for interventions in age-related diseases and cancer. The present invention relates to a method for treating senescence related disease in a subject in need thereof comprising administering said subject with a therapeutically effective amount of a modulator of Glycerol kinase (GK), Glycerol 3 phosphate phosphatase (G3PP), Ethanolamine-Phosphate Phospho-Lyase (ETNPPL) and/or Phosphate Cytidylyltransferase 2 (PCYT2).