incb-018424 and Hematologic-Neoplasms

incb-018424 has been researched along with Hematologic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for incb-018424 and Hematologic-Neoplasms

Article	Year
Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies. Journal of medicinal chemistry, 2019, 04-25, Volume: 62, Issue:8 Concurrent inhibition of Janus kinase (JAK) and histone deacetylase (HDAC) could potentially improve the efficacy of the HDAC inhibitors in the treatment of cancers and resolve the problem of HDAC inhibitor resistance in some tumors. Here, a novel series of pyrimidin-2-amino-pyrazol hydroxamate derivatives as JAK and HDAC dual inhibitors was designed, synthesized, and evaluated, among which 8m possessed potent and balanced activities against both JAK2 and HDAC6 with half-maximal inhibitory concentration at the nanomolar level. 8m exhibited improved antiproliferative and proapoptotic activities over SAHA and ruxolitinib in several hematological cell lines. Remarkably, 8m exhibited more potent antiproliferation effect than the combination of SAHA and ruxolitinib in HEL cells bearing JAK2 Topics: Animals; Binding Sites; Catalytic Domain; Drug Evaluation, Preclinical; Half-Life; Hematologic Neoplasms; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Janus Kinases; Male; Mice; Mice, Nude; Molecular Docking Simulation; Nitriles; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Xenograft Model Antitumor Assays	2019
Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines. Journal of medicinal chemistry, 2016, Sep-22, Volume: 59, Issue:18 Blockage of more than one oncoprotein or pathway is now a standard approach in modern cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM potent against HDACs 2 and 10, submicromolar potent against HDACs 1, 8, and 11, and >50-fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule. Topics: Antineoplastic Agents; Apoptosis; Bridged-Ring Compounds; Cell Line, Tumor; Cell Proliferation; Hematologic Neoplasms; Histone Deacetylase Inhibitors; Humans; Janus Kinase 2; Models, Molecular; Protein Kinase Inhibitors; Pyrimidines; Signal Transduction	2016

Article

Year

Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies.

Journal of medicinal chemistry, 2019, 04-25, Volume: 62, Issue:8

Concurrent inhibition of Janus kinase (JAK) and histone deacetylase (HDAC) could potentially improve the efficacy of the HDAC inhibitors in the treatment of cancers and resolve the problem of HDAC inhibitor resistance in some tumors. Here, a novel series of pyrimidin-2-amino-pyrazol hydroxamate derivatives as JAK and HDAC dual inhibitors was designed, synthesized, and evaluated, among which 8m possessed potent and balanced activities against both JAK2 and HDAC6 with half-maximal inhibitory concentration at the nanomolar level. 8m exhibited improved antiproliferative and proapoptotic activities over SAHA and ruxolitinib in several hematological cell lines. Remarkably, 8m exhibited more potent antiproliferation effect than the combination of SAHA and ruxolitinib in HEL cells bearing JAK2

Topics: Animals; Binding Sites; Catalytic Domain; Drug Evaluation, Preclinical; Half-Life; Hematologic Neoplasms; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Janus Kinases; Male; Mice; Mice, Nude; Molecular Docking Simulation; Nitriles; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Xenograft Model Antitumor Assays

2019

Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines.

Journal of medicinal chemistry, 2016, Sep-22, Volume: 59, Issue:18

Blockage of more than one oncoprotein or pathway is now a standard approach in modern cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM potent against HDACs 2 and 10, submicromolar potent against HDACs 1, 8, and 11, and >50-fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.

Topics: Antineoplastic Agents; Apoptosis; Bridged-Ring Compounds; Cell Line, Tumor; Cell Proliferation; Hematologic Neoplasms; Histone Deacetylase Inhibitors; Humans; Janus Kinase 2; Models, Molecular; Protein Kinase Inhibitors; Pyrimidines; Signal Transduction

2016