| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
S55746 hydrochloride targets BCL-2, an anti-apoptotic protein that is overexpressed in many cancers and contributes to tumor cell survival and chemoresistance. The compound acts as a potent and selective BCL-2 inhibitor with a Ki of 1.3 nM and a Kd of 3.9 nM.
|
|---|---|
| ln Vitro |
S55746 (0-1 μM) potently and selectively triggers cell death [1]. S55746 preferentially promotes apoptosis by inhibiting BCL-2 in a BAX/BAK-dependent manner [1].
In vitro, S55746 hydrochloride inhibits BCL-2 with a Ki of 1.3 nM and a Kd of 3.9 nM. The compound demonstrates efficacy in inducing cell death in various cancer cell lines, including those resistant to conventional treatments. It has antitumor activity with low toxicity. Detailed IC₅0 values against specific cancer cell lines are not extensively documented. |
| ln Vivo |
S55746 is an oral active BCL-2 inhibitor that is very effective and well-tolerated (even at doses up to 300 mg/kg) [1]. In the RS4;11 and Toledo models, S55746 (20–100 mg/kg, oral) suppresses xenograft growth in a dose- and time-dependent manner [1].
In vivo activity data for S55746 hydrochloride indicate antitumor activity with low toxicity. As an orally active BCL-2 inhibitor, the compound is expected to show efficacy in xenograft tumor models. Further in vivo efficacy studies in appropriate cancer models would be needed to fully characterize its antitumor activity and pharmacokinetic properties. |
| Enzyme Assay |
The in vitro BCL-2 binding assay uses recombinant BCL-2 protein and a fluorescently labeled BH3 peptide. Binding is measured by fluorescence polarization or AlphaScreen technology. Ki and Kd values are calculated from competition binding experiments with varying concentrations of S55746 hydrochloride. Selectivity against other BCL-2 family members (such as BCL-XL, MCL-1) is assessed similarly.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: H146 and RS4; 11 cell lines. Tested Concentrations: 0, 0.1, 0.3 and 1 μM. Incubation Duration: 72 hrs (hours). Experimental Results: After 72 hrs (hours) of treatment, RS4;11 cell death was effectively induced, with an IC50 of 71.6 nM. For in vitro cell-based assays, cancer cell lines (such as lymphoma, leukemia, or solid tumor lines) are cultured and treated with S55746 hydrochloride at various concentrations. Cell viability is measured using MTT, CellTiter-Glo, or Annexin V staining to assess apoptosis. BCL-2 inhibition is confirmed by measuring apoptosis markers such as caspase activation or cytochrome c release. Experiments are typically performed in triplicate. |
| Animal Protocol |
Animal/Disease Models: Female SCID/beige mice were subcutaneously (sc) (sc) implanted with 3×106 Toledo or RS4;11[1].
Doses: 20, 50, 100 mg/kg. Route of Administration: Orally administered daily for 7 days. Experimental Results: Significant antitumor activity was induced in a time- and dose-dependent manner. Animal/Disease Models: SCID/beige female mice bearing RS4;11 tumor xenografts [1]. Doses: 25 and 100 mg/kg. Route of Administration: Single po (oral gavage) treatment. Experimental Results: Concentrations of 25 and 100 mg/kg did not cause platelet loss in vivo. In vivo animal studies for S55746 hydrochloride typically involve xenograft mouse models using BCL-2-dependent cancer cell lines. Tumor-bearing mice are administered the compound orally at various doses. Tumor volume is measured periodically using calipers, and tumor growth inhibition is assessed relative to vehicle-treated controls. At study termination, tumors are harvested for histopathological analysis and assessment of apoptosis markers. Pharmacokinetic studies may also be performed. |
| ADME/Pharmacokinetics |
S55746 hydrochloride is orally active with good bioavailability. The compound has molecular weight approximately 747.3 g/mol. It is soluble in DMSO and supplied as a 10 mM ready-to-use solution. Purity is reported as high. Further detailed PK parameters (half-life, Cmax, AUC) would require dedicated studies. Storage at -20degC is recommended.
|
| Toxicity/Toxicokinetics |
Toxicological data for S55746 hydrochloride indicate low toxicity. As a research compound, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. BCL-2 inhibitors as a class may have potential effects on platelet function and hematopoiesis. Comprehensive toxicity profiling would be required for therapeutic development.
|
| References | |
| Additional Infomation |
S55746 hydrochloride (CAS# 1448525-91-4) is a potent, orally active, and selective BCL-2 inhibitor with a Ki of 1.3 nM and a Kd of 3.9 nM. It has antitumor activity with low toxicity. The compound is also known as BCL201 hydrochloride and is used in cancer research.
|
| Molecular Formula |
C43H43CLN4O6
|
|---|---|
| Molecular Weight |
747.277730226517
|
| Exact Mass |
746.287
|
| CAS # |
1448525-91-4
|
| Related CAS # |
S55746;1448584-12-0
|
| PubChem CID |
71696476
|
| Appearance |
White to yellow solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
54
|
| Complexity |
1250
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C(N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)(C1C=C2OCOC2=CC=1C1=CC(C(=O)N(C2C=CC=CC=2)C2C=CC(O)=CC=2)=C2CCCCN12)=O.Cl
|
| InChi Key |
RAUZIGXCAJHBEL-WAQYZQTGSA-N
|
| InChi Code |
InChI=1S/C43H42N4O6.ClH/c48-34-15-13-32(14-16-34)47(31-10-2-1-3-11-31)43(50)37-23-39(45-17-7-6-12-38(37)45)35-24-40-41(53-28-52-40)25-36(35)42(49)46-26-30-9-5-4-8-29(30)22-33(46)27-44-18-20-51-21-19-44/h1-5,8-11,13-16,23-25,33,48H,6-7,12,17-22,26-28H21H/t33-/m0./s1
|
| Chemical Name |
(S)-N-(4-hydroxyphenyl)-3-(6-(3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzo[d][1,3]dioxol-5-yl)-N-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide
hydrochloride
|
| Synonyms |
S55746 hydrochloride S 55746 hydrochloride S-55746
hydrochloride BLC201 hydrochloride BLC 201 hydrochloride BLC-201
hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~200 mg/mL (~267.64 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 5 mg/mL (6.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3382 mL | 6.6909 mL | 13.3819 mL | |
| 5 mM | 0.2676 mL | 1.3382 mL | 2.6764 mL | |
| 10 mM | 0.1338 mL | 0.6691 mL | 1.3382 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
