Sabutoclax
Sabutoclax is an inhibitor of pan-Bcl-2 family with IC50 values of 0.32, 0.31, 0.20 and 0.62 μM for Bcl-2, Bcl-xL, Mcl-1 and Bfl-1, respectively [1].
Sabutoclax is a derivative of apogossypolone. It showed a high binding affinity to Bcl-xL both in NMR binding assay and in ITC assay, with a Kd value of 0.11μM. Sabutoclax also showed better cell membrane permeability than other apogossypolone derivatives. In PC3 cells, sabutoclax inhibited cell growth with EC50 value of 0.13 μM. In human BP3 cell line, sabutoclax induced cell apoptosis with IC50 value of 0.049 μM. In mice bearing M2182 cancer xenografts, administration of sabutoclax significantly reduced the tumor size. At dose of 5 mg/kg, sabutoclax induced near complete tumor growth suppression [1].
References:
[1] Wei J, Stebbins J L, Kitada S, et al. BI-97C1, an optically pure Apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. Journal of medicinal chemistry, 2010, 53(10): 4166-4176.
- 1. Minieri V, De Dominici M, et al. "Targeting STAT5 or STAT5-Regulated Pathways Suppresses Leukemogenesis of Ph+ Acute Lymphoblastic Leukemia." Cancer Res. 2018 Oct 15;78(20):5793-5807. PMID:30154155
- 2. Mishra P J, Mishra P J, Merlino G. "Integrated Genomics Identifies miR-32/MCL-1 Pathway as a Critical Driver of Melanomagenesis: Implications for miR-Replacement and Combination Therapy[J]." PloS one, 2016, 11(11): e0165102. PMID:27846237
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 700.78 |
| Cas No. | 1228108-65-3 |
| Formula | C42H40N2O8 |
| Solubility | insoluble in H2O; ≥205.6 mg/mL in DMSO; ≥98.2 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2,3,5-trihydroxy-7-methyl-N-[(2R)-2-phenylpropyl]-6-[1,6,7-trihydroxy-3-methyl-5-[[(2R)-2-phenylpropyl]carbamoyl]naphthalen-2-yl]naphthalene-1-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=C(C(=C2C=C(C(=C(C2=C1)C(=O)NCC(C)C3=CC=CC=C3)O)O)O)C4=C(C=C5C(=C4O)C=C(C(=C5C(=O)NCC(C)C6=CC=CC=C6)O)O)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
PC-3 human prostate cancer cells, H460 human lung cancer cells, BP3 B-cell lymphoma cells, and mouse embryonic fibroblast cells |
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Reaction Conditions |
3 d incubation |
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Applications |
Sabutoclax potently inhibited cell growth of human prostate cancer (3 d), lung cancer (3 d), and lymphoma (1 ~ 2 d) cell lines, with EC50 values of 0.13, 0.56, and 0.049 μM, respectively. In addition, sabutoclax (overnight incubation) showed little cytotoxicity against bax-/-bak-/- mouse embryonic fibroblast cells at 30 μM, while it killed almost 70% wild-type mouse embryonic fibroblast cells at the same concentration. |
| Animal experiment:[1] | |
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Animal models |
Bcl-2 transgenic mice; human prostate cancer xenografts |
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Dosage form |
42 mg/kg for transgenic mice; 1, 3 or 5 mg/kg for the prostate cancer mouse xenograft model Administered intraperitoneally |
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Applications |
Sabutoclax displayed in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, sabutoclax represents a potential drug lead for the development of novel apoptosis-based therapies against cancer. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Wei J, Stebbins J L, Kitada S, et al. BI-97C1, an optically pure Apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. Journal of medicinal chemistry, 2010, 53(10): 4166-4176. |
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| Description | Sabutoclax(BI-97C1) is a inhibitor of Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 values of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively. | |||||
| Targets | Bcl-xL | Bcl-2 | Mcl-1 | Bfl-1 | ||
| IC50 | 0.31 μM | 0.32 μM | 0.20 μM | 0.62 μM | ||
Quality Control & MSDS
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