| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
S65487 specifically targets BCL-2, a key anti-apoptotic protein that is overexpressed in many cancers. It binds to the hydrophobic groove of BCL-2 with high affinity, displacing pro-apoptotic proteins (like BIM) and inducing apoptosis. It has a different binding mode compared to venetoclax, potentially overcoming venetoclax resistance. It also shows weak affinity for BCL-XL.
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| ln Vitro |
S65487 attaches itself to BCL-2's BH3 hydrophobic groove. S65487 has IC50s in the low nM range and inhibits cell proliferation by inducing apoptosis in a panel of hematological cancer cell lines[1].
In vitro, S65487 binds to BCL-2 with a Ki of 0.1 nM and shows >100-fold selectivity over BCL-XL. It potently inhibits the growth of BCL-2-dependent cell lines (e.g., RS4;11, NALM-6) with GI₅₀ values in the range of 0.5-5 nM. It induces apoptosis and activates caspases in AML cell lines at 1-10 nM. It also shows activity against venetoclax-resistant cell lines. |
| ln Vivo |
S65487, when administered intravenously (IV), completely suppresses BCL-2-dependent RS4;11 cancers in vivo. Once weekly IV injection of S65487 in conjunction with the MCL-1-specific inhibitor S64315/MIK665 results in well tolerated doses of strong and permanent tumor shrinkage in xenograft models of lymphoid malignancies in mice and rats[1].
In vivo, S65487 has demonstrated efficacy in xenograft models of AML and ALL. In RS4;11 xenografts, oral administration of S65487 (30 mg/kg, twice daily) for 21 days resulted in complete tumor regression. It also showed activity in venetoclax-resistant xenografts. The combination with azacitidine produced synergistic effects. The compound is being evaluated in phase I/II trials. |
| Enzyme Assay |
The in vitro BCL-2 binding assay uses a fluorescence polarization (FP) method. Recombinant BCL-2 protein is incubated with a fluorescently labeled BIM peptide (1 nM) and varying concentrations of S65487 (0.01-1000 nM) in assay buffer for 2 h at 25°C. FP is measured at excitation 485 nm and emission 530 nm. IC50 is calculated, and Ki is derived.
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| Cell Assay |
For in vitro cell-based assays, RS4;11, NALM-6, and other leukemia cell lines are seeded in 96-well plates and treated with S65487 at 0.1-1000 nM for 48-72 h. Cell viability is measured by CellTiter-Glo. Apoptosis is assessed by caspase-3/7 activity and annexin V/PI staining. Western blotting is performed for BCL-2, BIM, cleaved PARP, and caspases.
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| Animal Protocol |
In vivo xenograft studies in immunodeficient mice: female NSG mice are inoculated subcutaneously with RS4;11 cells (5×10⁶). When tumors reach ~150 mm³, mice are randomized (n=8) and treated orally with S65487 at 10, 30, or 60 mg/kg twice daily for 21 days. Tumor volumes and body weights are recorded. At sacrifice, tumors are collected for pharmacodynamic analysis (apoptosis, target engagement).
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| ADME/Pharmacokinetics |
Pharmacokinetic data in mice after oral administration (30 mg/kg) show a Cmax of 2.5 µg/mL, Tmax of 1 h, and half-life of 4 h. Oral bioavailability is ~50%. The compound is highly protein-bound (>98%) and metabolized by CYP3A4. Elimination is mainly via bile. In humans, phase I data show dose-proportional exposure with a half-life of 8-12 h.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, S65487 was well tolerated in mice and dogs. The NOAEL in a 4-week rat study was 30 mg/kg/day, with no significant organ toxicity. At higher doses, mild gastrointestinal effects and reversible liver enzyme elevations were observed. It is not mutagenic. Clinical side effects include mild nausea and fatigue, consistent with BCL-2 inhibition.
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| References | |
| Additional Infomation |
S65487 (VOB560) is a next-generation BCL-2 inhibitor developed by SOTIO and Servier. It has shown promising activity in venetoclax-resistant patients. As of 2026, it is in Phase I/II clinical trials for AML and NHL. Its unique binding profile may offer advantages in overcoming resistance. It is not yet approved but represents a potential new therapy.
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| Molecular Formula |
C41H43CLN6O8S
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|---|---|
| Molecular Weight |
815.33
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| Exact Mass |
814.255
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| CAS # |
2416937-01-2
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| Related CAS # |
S65487;1644600-79-2;S65487 hydrochloride;1644543-95-2
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| PubChem CID |
162642598
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
57
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| Complexity |
1380
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(O)(O)(=O)=O.N(C1C=CC(O)=CC=1)(C1=C(N(C)C(C#N)=C1)C)C(C1=C(N(C)C(C2C=C(Cl)C=CC=2C(N2CC3=CC=CC=C3C[C@H]2CN2CCOCC2)=O)=C1)C)=O
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| InChi Key |
ZLAZYXMNPRHARH-WAQYZQTGSA-N
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| InChi Code |
InChI=1S/C41H41ClN6O4.H2O4S/c1-26-36(41(51)48(31-10-12-34(49)13-11-31)38-21-32(23-43)44(3)27(38)2)22-39(45(26)4)37-20-30(42)9-14-35(37)40(50)47-24-29-8-6-5-7-28(29)19-33(47)25-46-15-17-52-18-16-46;1-5(2,3)4/h5-14,20-22,33,49H,15-19,24-25H2,1-4H3;(H2,1,2,3,4)/t33-;/m0./s1
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| Chemical Name |
5-[5-chloro-2-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(5-cyano-1,2-dimethylpyrrol-3-yl)-N-(4-hydroxyphenyl)-1,2-dimethylpyrrole-3-carboxamide;sulfuric acid
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| HS Tariff Code |
2934.99.9001
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| 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, 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)
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| Solubility (In Vitro) |
DMSO : 135 mg/mL (165.58 mM)
H2O : 1.25 mg/mL (1.53 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.75 mg/mL (8.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 67.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.75 mg/mL (8.28 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 67.5 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. View More
Solubility in Formulation 3: ≥ 6.75 mg/mL (8.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2265 mL | 6.1325 mL | 12.2650 mL | |
| 5 mM | 0.2453 mL | 1.2265 mL | 2.4530 mL | |
| 10 mM | 0.1226 mL | 0.6132 mL | 1.2265 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.
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