AMG-176 (Synonyms: AMG-176；Tapotoclax) |
Catalog No.GC19452
One-Click Copy Product Info
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AMG-176 (Tapotoclax) is a potent, selective and orally active MCL-1 inhibitor, with a Ki of 0.13 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1883727-34-1
Sample solution is provided at 25 µL, 10mM.
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AMG-176 is a selective myeloid cell leukemia-1 (MCL-1) inhibitor (Ki=0.13nM). AMG-176 disrupts the interaction between MCL-1 and BIM or BAK. AMG-176 rapidly induces apoptosis in hematopoietic tumor cells. AMG-176 can be used in studies related to hematologic malignancies such as multiple myeloma, acute myeloid leukemia, and B-cell lymphoma. AMG-176 exhibits synergistic antitumor activity with the BCL-2 inhibitor venetoclax in AML models[1-4].
In vitro, treatment of MEC1 and Mino cells with 500nM AMG-176 for 12-24 hours upregulated Mcl-1 protein levels, increased cleaved PARP expression, and induced apoptosis[5]. Treatment of CLL lymphocytes with 100nM-300nM AMG-176 for 24 hours caused cell death, increased mitochondrial levels of Mcl-1, Bax, and Bak proteins, reduced mitochondrial cytochrome C while increasing cytosolic cytochrome C, and induced procaspase-3 cleavage and PARP cleavage[6]. Co-treatment of C002M, C057M, and C065M cells with 5µM AMG-176 and 2µM I-BET151 for 72 hours increased the proportion of apoptotic cells[7].
In vivo, SCID mice bearing subcutaneous Ramos cell xenografts received oral gavage of 60mg/kg AMG-176 on days 3, 4, 10, and 11 (four doses total). AMG-176 significantly prolonged mouse survival and reduced subcutaneous tumor volume[8]. NSG mice bearing mixed TP53-WT Molm13 and TP53-R248W Molm13 cell xenografts via tail vein injection received oral gavage of 30mg/kg AMG-176 on days 2 and 3 of each week until survival endpoint. AMG-176 reduced circulating Molm13 cells[9]. NSG-SGM3 mice receiving tail vein injection of T-cell-depleted bone marrow mononuclear cells from myelodysplastic syndrome patients received oral gavage of 30mg/kg AMG-176 for 2 consecutive weeks (first two days of each week). AMG-176 reduced the engraftment rate of exogenous CD45+ cells in mouse bone marrow[10].
References:
[1] Caenepeel S, Brown SP, Belmont D, et al. AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. Cancer Discov. 2018 Dec;8(12):1582-1597.
[2] Kotschy A, Szlavik Z, Murray J, et al. MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents. Acta Pharm Sin B. 2021;11(1):1-26.
[3] Zhang W, Konopleva M. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy. Adv Cancer Res. 2021;151:1-62.
[4] La Vecchia S, Doshi S, Antonoglou P, et al. Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia. Sci Adv. 2025 Oct 17;11(42):eadx8662.
[5] Tantawy SI, Sarkar A, Hubner S, et al. Mechanisms of MCL-1 protein stability induced by MCL-1 antagonists in B-cell malignancies. Clin Cancer Res. 2023 Jan 17;29(2):446-457.
[6] Yi X, Sarkar A, Kismali G, et al. AMG-176, an Mcl-1 antagonist, shows preclinical efficacy in chronic lymphocytic leukemia. Clin Cancer Res. 2020 Jul 15;26(14):3856-3867.
[7] Tseng HY, Dreyer J, Emran AA, et al. Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma. Int J Cancer. 2020;1-14.
[8] Torka P, Russell T, Mavis C, et al. AMG176, an MCL-1 Inhibitor, is Active in Pre-clinical Models of Aggressive B-cell Lymphomas. Leuk Lymphoma. 2023 Jun;64(6):1175-1185.
[9] Carter BZ, Mak PY, Tao W, et al. Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant acute myeloid leukemia to individual BH3 mimetics. Blood Cancer J. 2023 Apr 24;13(1):57.
[10] Chen S. Dissecting the Mechanisms of Venetoclax Resistance in Myelodysplastic Syndromes. The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. 2021 Aug.
| Cell experiment [1]: | |
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Cell lines |
C002M cells (human melanoma cell line), C057M cells (human melanoma cell line), C065M cells (human melanoma cell line) |
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Preparation Method |
C002M, C057M and C065M cells were cultured in RPMI-1640 medium supplemented with 10% FBS at 37°C, 5% CO2. Cells were treated with 5µM AMG-176 and 2µM I-BET151 alone or in combination for 72 hours. After treatment, apoptotic cell death was quantified by Annexin V and propidium iodide staining followed by flow cytometry analysis. |
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Reaction Conditions |
5µM; 72h |
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Applications |
AMG-176 combined with I-BET151 induced synergistic apoptotic cell death in C002M, C057M and C065M cells. AMG-176 alone at 5µM did not induce significant apoptotic cell death in C002M, C057M and C065M cells over 72 hours. |
| Animal experiment [2]: | |
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Animal models |
6-8-week-old SCID mice (SCID C.B-Igh-1 b/lcrTac-Prkdcscid/Ros) bearing subcutaneous Ramos human Burkitt lymphoma xenografts |
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Preparation Method |
Mice were inoculated subcutaneously with 10×10⁶ Ramos cells on day 0. When tumors became palpable on day 18, mice were divided into cohorts. AMG-176 was administered by oral gavage at 60mg/kg in 100μL on days 3,4,10,11. Survival was defined as time to tumor size >2cm; subcutaneous tumor volume was measured serially. |
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Dosage form |
60mg/kg; p.o. gavage; days 3,4,10,11 (total of 4 doses) |
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Applications |
AMG-176 at 60mg/kg prolonged survival in Ramos subcutaneous xenograft-bearing SCID mice. AMG-176 at 60mg/kg reduced subcutaneous Ramos tumor volume. |
References: [1] Tseng HY, Dreyer J, Emran AA, et al. Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma. Int J Cancer. 2020;1-14. [2] Torka P, Russell T, Mavis C, et al. AMG176, an MCL-1 inhibitor, is active in pre-clinical models of aggressive B-cell lymphomas. Leuk Lymphoma. 2023 Jun;64(6):1175-1185. | |
| Cas No. | 1883727-34-1 | SDF | |
| Synonyms | AMG-176；Tapotoclax | ||
| Canonical SMILES | ClC1=CC=C2C(CCC[C@@]23CN(C[C@@](CC4)([H])[C@]4([H])[C@H](/C=C/C[C@H](C)[C@H]5C)OC)C6=CC(C(NS5(=O)=O)=O)=CC=C6OC3)=C1 | ||
| Formula | C33H41ClN2O5S | M.Wt | 613.21 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6308 mL | 8.1538 mL | 16.3076 mL |
| 5 mM | 326.2 μL | 1.6308 mL | 3.2615 mL |
| 10 mM | 163.1 μL | 815.4 μL | 1.6308 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)