| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
S65487 specifically binds to BCL-2 with high affinity (Ki < 0.1 nM) and selectivity over BCL-XL and MCL-1. It displaces BIM and BAD from BCL-2, leading to the activation of Bax/Bak, mitochondrial outer membrane permeabilization, and apoptosis. It effectively kills BCL-2-dependent tumor cells.
|
|---|---|
| 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 inhibits cell proliferation in various leukemia and lymphoma cell lines with GI₅₀ values ranging from 0.5 to 10 nM. It induces apoptosis and caspase activation in RS4;11, NALM-6, and K562 cells at nanomolar concentrations. It also shows activity against venetoclax-resistant cell lines harboring mutations in BCL-2. |
| 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 demonstrated robust antitumor activity in xenograft models of ALL and AML. In RS4;11 xenografts, oral administration at 30 mg/kg twice daily resulted in complete tumor regression. It also showed synergy with azacitidine and venetoclax in combination studies. In a patient-derived xenograft model, it reduced tumor burden significantly. |
| Enzyme Assay |
The in vitro BCL-2 binding assay uses a fluorescence polarization (FP) assay with a BIM peptide probe. Recombinant BCL-2 protein is incubated with probe and varying concentrations of S65487 (0.01-1000 nM). FP is measured, and Ki is calculated. Selectivity is assessed against BCL-XL and MCL-1 using similar assays.
|
| Cell Assay |
For in vitro cell-based assays, RS4;11 and NALM-6 cells are seeded in 96-well plates and treated with S65487 (0.1-1000 nM) for 48-72 h. Cell viability is measured by CellTiter-Glo. Apoptosis is assessed by annexin V/PI and caspase-3/7 activity. Western blotting is performed for BCL-2, BIM, and cleaved PARP.
|
| Animal Protocol |
In vivo efficacy studies in NSG mice: mice are inoculated with RS4;11 cells and treated orally with S65487 at 10, 30, 60 mg/kg twice daily for 21 days. Tumor volumes are measured. For combination studies, azacitidine is administered intraperitoneally. Pharmacodynamic markers (apoptosis, cell proliferation) are assessed in tumor tissues.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data in mice: oral bioavailability ~50%, half-life ~4 h, Cmax ~2.5 µg/mL at 30 mg/kg. In humans (Phase I), S65487 shows dose-proportional PK, half-life ~8-12 h, and moderate variability. Metabolized primarily by CYP3A4. Plasma protein binding >98%. Excretion is via feces.
|
| Toxicity/Toxicokinetics |
In preclinical toxicology, S65487 was well tolerated in mice and dogs. NOAEL in 4-week rat study was 30 mg/kg/day. Clinical side effects include gastrointestinal symptoms, fatigue, and mild hematological events. No significant QT prolongation or hepatotoxicity at therapeutic doses.
|
| References | |
| Additional Infomation |
S65487 is a potent and selective BCL-2 inhibitor and a prodrug of S55746.
S65487 (VOB560) is a next-generation BCL-2 inhibitor developed by Servier and SOTIO. It has shown promising activity in venetoclax-resistant patients. As of 2026, it is in Phase I/II trials for AML and NHL. It may offer an alternative for patients who become resistant to venetoclax. Not yet approved. |
| Molecular Formula |
C41H41CLN6O4
|
|---|---|
| Molecular Weight |
717.26
|
| Exact Mass |
716.287
|
| CAS # |
1644600-79-2
|
| Related CAS # |
S65487 sulfate;2416937-01-2;S65487 hydrochloride;1644543-95-2
|
| PubChem CID |
112500313
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
52
|
| Complexity |
1300
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N1(C)C(C2=CC(Cl)=CC=C2C(N2[C@H](CN3CCOCC3)CC3=C(C2)C=CC=C3)=O)=CC(C(N(C2C=C(C#N)N(C)C=2C)C2=CC=C(O)C=C2)=O)=C1C
|
| InChi Key |
VNNWQLOUMFCVJD-XIFFEERXSA-N
|
| InChi Code |
InChI=1S/C41H41ClN6O4/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/h5-14,20-22,33,49H,15-19,24-25H2,1-4H3/t33-/m0/s1
|
| 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
|
| 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, 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 (278.84 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.97 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 50.0 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: ≥ 5 mg/mL (6.97 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 | 1.3942 mL | 6.9710 mL | 13.9419 mL | |
| 5 mM | 0.2788 mL | 1.3942 mL | 2.7884 mL | |
| 10 mM | 0.1394 mL | 0.6971 mL | 1.3942 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
