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| | N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide Basic information |
| | N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide Chemical Properties |
| storage temp. | Store at -20°C | | solubility | Water:50.0(Max Conc. mg/mL);97.39(Max Conc. mM) | | form | Solid | | color | White to off-white |
| | N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide Usage And Synthesis |
| Uses | PIM447 dihydrochloride (LGH447 dihydrochloride) is a potent, orally available, and selective pan-PIM kinase inhibitor, with Ki values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 dihydrochloride displays dual antimyeloma and bone-protective effects. PIM447 dihydrochloride induces apoptosis[1][2]. | | in vivo | PIM447 (oral gavage; 100 mg/kg; 5 times/week) clearly controlls tumor progression and the serum levels of hIgλ secreted by RPMI-8226-luc cells in mouse model of bone marrow-disseminated human multiple myeloma[1]. | Animal Model: | RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ-/-(NSG) mice[1] | | Dosage: | 100 mg/kg | | Administration: | oral gavage; 100 mg/kg; 5 times/week | | Result: | Was well tolerated, as the body weight of mice did not decrease by more than 10%.
Increased bone volume density and trabecular number and reduced trabecular separation relative to vehicle group. |
| | IC 50 | PIM1; PIM2; PIM3 | | References | [1] Paíno T et al. The novel pan-PIM kinase inhibitor, PIM447, displays dual anti-myeloma and bone protective effects, and potently synergizes with current standards of care. Clin Cancer Res. 2016 Jul 20. DOI:10.1158/1078-0432.CCR-16-0230
[2] Burger MT et al. Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.
J Med Chem. 2015 Nov 12;58(21):8373-86. DOI:10.1021/acs.jmedchem.5b01275
[3] Peters TL et al. Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447.
Oncotarget. 2016 Aug 20 DOI:10.18632/oncotarget.11457 |
| | N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide Preparation Products And Raw materials |
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