A-1210477
Modify Date: 2024-01-02 11:21:52
A-1210477 structure
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Common Name | A-1210477 | ||
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| CAS Number | 1668553-26-1 | Molecular Weight | 850.037 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | 1027.4±65.0 °C at 760 mmHg | |
| Molecular Formula | C46H55N7O7S | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 575.1±34.3 °C | |
Use of A-1210477A-1210477 is a potent and selective inhibitor of MCL-1 with a Ki of 0.45 nM. |
| Name | 7-[5-[[4-[4-[(Dimethylamino)sulfonyl]-1-piperazinyl]phenoxy]methyl]-1,3-dimethyl-1H-pyrazol-4-yl]-1-[2-(4-morpholinyl)ethyl]-3-[3-(1-naphthalenyloxy)propyl]-1H-indole-2-carboxylic acid |
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| Synonym | More Synonyms |
| Description | A-1210477 is a potent and selective inhibitor of MCL-1 with a Ki of 0.45 nM. |
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| Related Catalog | |
| Target |
Mcl-1:0.45 nM (Ki) Bcl-2:132 nM (Ki) Bfl-1:660 nM (Ki) Bcl-W:2280 nM (Ki) |
| In Vitro | A-1210477 (10 μM) reduces the amount of BIM co-immunoprecipitated with MCL-1 antibody, and triggers MCL-1 elevation in a variety of cancer cell lines, including the breast cancer cell line HCC-1806. A-1210477 inhibits MCL-1-NOXA interactions with an IC50 of approximately 1 μM, while having no effect on BCL-2-BIM or BCL-XL-BCL-XS interactions. The NSCLC cell lines H2110 and H23 are sensitive to A-1210477 with cell viability IC50<10 μM, confirming that A-1210477 can kill MCL-1-dependent cell lines[1]. A-1210477 induces extensive concentration-dependent apoptosis in H929 cells following a brief (4 h) exposure. A-1210477 interacts with MCL-1 with Kd of appr 740 nM. A-1210477 (10 μM) induces extensive mitochondrial fragmentation in a DRP-1-dependent manner[2]. A-1210477 upregulates MCL-1 expression in BRAF-mutant CRC cells and in the melanoma cell line A375 in a dose-dependent manner. A-1210477 releases BAK from MCL-1 and cobimetinib induces BIM that is required for BAX activation[3]. A-1210477 (0, 5, 10 and 15 μM) has minimal effect on cell viability but substantially sensitizes resistant BCL2High NHL cell lines to navitoclax[4]. |
| Kinase Assay | TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride, and 1 mM DTT (pH 7.5) for BCL-XL.6 For MCL-1 assays, GST-tagged MCL-1 (1 nM) is mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters. |
| Cell Assay | Adherent cell lines are seeded at 50 000 cells per well in 96-well plates and treated for 48 h with compounds diluted in half-log steps starting at 30 μM and ending at 0.001 μM. Multiple myeloma cell lines are seeded at 15 000-20 000 cells per well and treated similarly. Effects on proliferation and viability are determined using CellTiter-Glo reagent from Promega according to the manufacturer's instructions. IC50 values are determined by non-linear regression analysis of the concentration response data. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 1027.4±65.0 °C at 760 mmHg |
| Molecular Formula | C46H55N7O7S |
| Molecular Weight | 850.037 |
| Flash Point | 575.1±34.3 °C |
| Exact Mass | 849.388367 |
| LogP | 4.68 |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.655 |
| Storage condition | 2-8°C |
| 7-[5-({4-[4-(Dimethylsulfamoyl)-1-piperazinyl]phenoxy}methyl)-1,3-dimethyl-1H-pyrazol-4-yl]-1-[2-(4-morpholinyl)ethyl]-3-[3-(1-naphthyloxy)propyl]-1H-indole-2-carboxylic acid |
| 1H-Indole-2-carboxylic acid, 7-[5-[[4-[4-[(dimethylamino)sulfonyl]-1-piperazinyl]phenoxy]methyl]-1,3-dimethyl-1H-pyrazol-4-yl]-1-[2-(4-morpholinyl)ethyl]-3-[3-(1-naphthalenyloxy)propyl]- |
| A-1210477 |