| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
IC50: 0.31 μM (Bcl-XL), 0.32 μM (Bcl-2), 0.20 μM (Mcl-1), 0.62 μM (Bfl-1); EC50: 0.13 (human prostate cancer cell lines), 0.56 (lung cancer cell lines), 0.049 μM (lymphoma cell lines)[1].
Bcl-2 family proteins: Bcl-XL, Bcl-2, Mcl-1, and Bfl-1. (S)-Sabutoclax is a pan-active inhibitor that binds to the BH3-binding groove of multiple antiapoptotic Bcl-2 family members. Bcl-2 and Bcl-XL are well-established anti-apoptotic proteins that are overexpressed in various hematological malignancies and solid tumors. Mcl-1 is another important anti-apoptotic protein that is frequently upregulated in cancers and is associated with resistance to Bcl-2-specific inhibitors such as venetoclax. Bfl-1 (also known as A1) is an anti-apoptotic protein that is less well-studied but is implicated in certain hematological malignancies. By inhibiting all four of these proteins, (S)-Sabutoclax overcomes the redundancy in the Bcl-2 family that can limit the efficacy of more selective inhibitors. |
|---|---|
| ln Vitro |
(S)-Sabutoclax inhibits BH3 peptide binding to Bcl-XL with an IC50 of 0.31 μM, to Bcl-2 with an IC50 of 0.32 μM, to Mcl-1 with an IC50 of 0.20 μM, and to Bfl-1 with an IC50 of 0.62 μM. These sub-micromolar IC50 values demonstrate that (S)-Sabutoclax is a potent inhibitor of multiple antiapoptotic Bcl-2 family proteins. The compound potently inhibits the growth of human cancer cell lines: prostate cancer (EC50: 0.13 μM), lung cancer (EC50: 0.56 μM), and lymphoma (EC50: 0.049 μM). The low EC50 values, particularly for lymphoma cells (49 nM), indicate that (S)-Sabutoclax is highly effective at inducing cell death in cancer cells that depend on Bcl-2 family proteins for survival. The mechanism of action involves binding to the BH3-binding groove of antiapoptotic proteins, thereby displacing pro-apoptotic BH3-only proteins (such as Bim and Bad) and triggering the activation of Bax and Bak, which leads to mitochondrial outer membrane permeabilization and apoptosis.
|
| ln Vivo |
(S)-Sabutoclax exhibits broad-spectrum anti-tumor activity in preclinical models by inducing apoptosis through inhibition of multiple Bcl-2 family anti-apoptotic proteins. It shows potent growth inhibition across various human cancer cell lines, including prostate, lung, and lymphoma. The pan-active profile of (S)-Sabutoclax distinguishes it from selective Bcl-2 inhibitors like venetoclax, which only targets Bcl-2 and is less effective against cancers that depend on Mcl-1 or Bcl-XL for survival. By targeting Bcl-XL, Mcl-1, and Bfl-1 in addition to Bcl-2, (S)-Sabutoclax has the potential to overcome resistance mechanisms that limit the efficacy of selective inhibitors. Detailed in vivo efficacy data (e.g., tumor growth inhibition in xenograft models) are not extensively reported in the available literature but are expected based on the potent in vitro activity.
|
| Enzyme Assay |
Fluorescence polarization (FP) competition assays are performed using fluorescently labeled BH3 peptides (e.g., FITC-labeled Bim BH3 peptide) incubated with recombinant Bcl-2 family proteins (Bcl-XL, Bcl-2, Mcl-1, Bfl-1) and varying concentrations of (S)-Sabutoclax. Binding of the fluorescent BH3 peptide to the Bcl-2 protein results in high fluorescence polarization due to the slow tumbling of the large protein-peptide complex. Displacement of the peptide by (S)-Sabutoclax reduces fluorescence polarization. The decrease in fluorescence polarization is measured, and IC50 values for inhibition of BH3 peptide binding are determined by fitting dose-response curves.
|
| Cell Assay |
Human cancer cell lines (prostate, lung, lymphoma) are treated with (S)-Sabutoclax at graded concentrations for 48-72 hours. Cell viability is assessed using standard assays such as MTT or CellTiter-Glo (luciferase-based ATP measurement) to determine EC50 values. Apoptosis is confirmed by Annexin V/PI staining (flow cytometry) and caspase activation assays (e.g., caspase-3/7 activity measured by fluorogenic substrates). Western blotting for cleaved PARP and cleaved caspase-3 is performed to confirm apoptotic cell death. The effects of (S)-Sabutoclax on mitochondrial membrane potential (ΔΨm) can also be assessed using fluorescent dyes such as JC-1.
|
| Animal Protocol |
Mouse xenograft models bearing human tumor xenografts (e.g., prostate, lung, lymphoma) are administered (S)-Sabutoclax via intraperitoneal or intravenous routes. Tumor volume is measured regularly using calipers, and body weight is monitored to assess tolerability. At study endpoint, tumors are collected for histopathological analysis (e.g., H&E staining) and biomarker evaluation (e.g., immunohistochemistry for cleaved caspase-3, PARP, and Ki-67) to confirm apoptosis induction and assess antitumor efficacy. The pan-active Bcl-2 inhibitor profile of (S)-Sabutoclax is expected to provide broad antitumor activity in vivo.
|
| ADME/Pharmacokinetics |
Predicted to have moderate to poor oral bioavailability typical of apogossypol derivatives; likely administered via parenteral routes (intraperitoneal or intravenous) for in vivo studies. High plasma protein binding is expected due to the lipophilic nature of the compound. Metabolic clearance is mediated by hepatic CYP450 enzymes, with potential for extensive metabolism. Standard pharmacokinetic parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution) are evaluated in rodents following intravenous and oral administration. Formulation in suitable vehicles (e.g., DMSO/PEG400/saline, or cyclodextrin-based formulations) is required for in vivo administration. Detailed PK data specific to (S)-Sabutoclax are not extensively reported in the available literature.
|
| Toxicity/Toxicokinetics |
Expected to have an acceptable safety profile in preclinical species at therapeutic doses. Potential dose-limiting toxicities may include gastrointestinal effects and hematological changes related to on-target Bcl-2 inhibition in normal tissues. Bcl-2 family proteins are important for the survival of certain normal cell populations, including hematopoietic cells and epithelial cells. Thrombocytopenia (low platelet counts) is a known dose-limiting toxicity of Bcl-2 inhibitors due to the dependence of platelets on Bcl-XL for survival. Mcl-1 inhibition may affect other tissues. Standard toxicology studies (acute and repeat-dose) in rodents and non-rodents are required to establish the safety margin and identify target organs of toxicity. As a research compound, detailed toxicology data are not publicly available.
|
| References | |
| Additional Infomation |
(S)-Sabutoclax is a research-grade pan-Bcl-2 inhibitor for cancer research. Molecular formula: C42H42N2O8S, molecular weight: 732.84. Purity: 98.03%. It is an optically pure (S)-enantiomer of BI-97C1 used in apoptosis and oncology research. Synonyms: (S)-BI-97C1. The compound inhibits BH3 peptide binding to Bcl-XL (IC50: 0.31 μM), Bcl-2 (IC50: 0.32 μM), Mcl-1 (IC50: 0.20 μM), and Bfl-1 (IC50: 0.62 μM), and potently inhibits human prostate cancer (EC50: 0.13 μM), lung cancer (EC50: 0.56 μM), and lymphoma (EC50: 0.049 μM) cell lines. For research use only, not for human therapeutic use.
|
| Molecular Formula |
C42H40N2O8
|
|---|---|
| Molecular Weight |
700.775611877441
|
| Exact Mass |
700.278
|
| CAS # |
1228178-73-1
|
| PubChem CID |
46236925
|
| Appearance |
Light yellow to brown solid powder
|
| LogP |
8.9
|
| Hydrogen Bond Donor Count |
8
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
52
|
| Complexity |
1100
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC1=CC2=C(C(=C(C=C2C(=C1C3=C(C4=CC(=C(C(=C4C=C3C)C(=O)NC[C@H](C)C5=CC=CC=C5)O)O)O)O)O)O)C(=O)NC[C@H](C)C6=CC=CC=C6
|
| InChi Key |
RAYNZUHYMMLQQA-ZEQRLZLVSA-N
|
| InChi Code |
InChI=1S/C42H40N2O8/c1-21-15-27-29(17-31(45)39(49)35(27)41(51)43-19-23(3)25-11-7-5-8-12-25)37(47)33(21)34-22(2)16-28-30(38(34)48)18-32(46)40(50)36(28)42(52)44-20-24(4)26-13-9-6-10-14-26/h5-18,23-24,45-50H,19-20H2,1-4H3,(H,43,51)(H,44,52)/t23-,24-/m0/s1
|
| 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
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~30 mg/mL (~40.94 mM; with sonication)
H2O :< 0.1 mg/mL (insoluble) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 3 mg/mL (4.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 30.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4270 mL | 7.1349 mL | 14.2698 mL | |
| 5 mM | 0.2854 mL | 1.4270 mL | 2.8540 mL | |
| 10 mM | 0.1427 mL | 0.7135 mL | 1.4270 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
