| 包装 | 价格(元) |
| 1mg | 电议 |
| 5mg | 电议 |
Cell lines | C002M and C057M melanoma cell lines |
Preparation Method | C002M and C057M were treated with the MCL1 inhibitor (AMG-176, 5 μM) for 72 hours and cell death was measured by Annexin V staining. |
Reaction Conditions | AMG-176 5uM; 72h |
Applications | AMG-176 has a weak ability to induce apoptosis in C002M melanoma cell line, but a strong ability to induce apoptosis in C057M melanoma cell line. AMG-176 has a synergistic effect with I-BET151 in these two melanoma cell lines. |
Animal models | Human MCL1 Knock-In Mice |
Preparation Method | Ultiple myeloma cells (cell line OPM-2 luc) were injected s.c. in the right flank of mice (5 × 106 cells). Animals were randomized into groups (n = 10 per group). Animals were then orally administered with AMG-176 daily, 2×/week, or 1×/week. |
Dosage form | 10mg/kg;20 mg/kg;30 mg/kg; 60mg/kg. 2h-24h |
Applications | Dose-dependent activation of the intrinsic apoptosis pathway in OPM-2 xenografts, as measured by activated BAK, cleaved caspase-3, and cleaved PARP, was detected as early as 2 hours after oral administration of AMG-176, with sustained cleaved PARP and activated BAK detectable through 12 hours and cleaved caspase-3 through 24 hours. Immunohistochemistry analysis revealed a similar dose-dependent increase in cleaved caspase-3. |
| 产品描述 | AMG-176 (Tapotoclax) is a potent, selective and orally active MCL-1 inhibitor, with a Ki of 0.13 nM. AMG-176 is a potent antagonist of Mcl-1; in cell free system the Ki value is <1 nM. In whole cells, the drug was tested in different leukemias, lymphoma, and multiple myeloma cell lines[1]. AMG-176 incubations resulted in time- and dose-dependent CLL cell death. At 100 and 300 nmol/L, there was 30% and 45% cell death at 24 hours. These concentrations did not result in significant cell death in normal hematopoietic cells. Presence of stroma did not affect AMG-176-induced CLL cell death[4].AMG-176 induced cell death was inversely correlated with endogenous McL-1 levels[5]. AMG-176 has a weak ability to induce apoptosis in C002M melanoma cell line, but a strong ability to induce apoptosis in C057M melanoma cell line. AMG-176 has a synergistic effect with I-BET151 in these two melanoma cell lines[2]. AMG-176 completely neutralized the survival effect of the IDO1/Kyn/AHR pathway in CLL cells[6]. AMG-176 Is Efficacious in Multiple Myeloma. In vivo, Dose-dependent activation of the intrinsic apoptosis pathway in OPM-2 xenografts, as measured by activated BAK, cleaved caspase-3, and cleaved PARP, was detected as early as 2 hours after oral administration of AMG 176, with sustained cleaved PARP and activated BAK detectable through 12 hours and cleaved caspase-3 through 24 hours. Immunohistochemistry analysis revealed a similar dose-dependent increase in cleaved caspase-3[3]. References: |
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