| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
B-cell lymphoma 2 (Bcl-2); inhibits the BCL-2/BAX interaction, promoting apoptosis; active against BCL-2 mutations (G101V, D103Y); poor affinity for MCL-1, BFL-1, and BCL-XL.
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|---|---|
| ln Vitro |
S65487 hydrochloride attaches itself to BCL-2's BH3 hydrophobic groove. S65487 hydrochloride has IC50s in the low nM range and inhibits cell proliferation in a panel of hematological cancer cell lines via inducing apoptosis[1].
In vitro, S65487 hydrochloride shows IC50 values in the low nanomolar range for inhibition of BCL-2. It effectively inhibits cell proliferation in a panel of hematological cancer cell lines by inducing apoptosis. The compound is active against BCL-2 mutations such as G101V and D103Y, while showing poor affinity for MCL-1, BFL-1, and BCL-XL (IC50 >1 uM), providing a favorable selectivity profile. |
| ln Vivo |
S65487 hydrochloride causes total remission of BCL-2-dependent RS4;11 tumors in vivo following a single intravenous (IV) injection. Once weekly IV treatment of S65487 hydrochloride 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 hydrochloride causes complete remission of BCL-2-dependent RS4;11 tumors following a single intravenous injection. The compound demonstrates significant antitumor activity in various xenograft models of hematological malignancies, including acute lymphoblastic leukemia and lymphoma. |
| Enzyme Assay |
BCL-2/BAX binding assay: Recombinant BCL-2 protein (50 nM) is incubated with biotinylated BAX BH3 peptide (10 nM) and S65487 hydrochloride (0.01-1000 nM) in 50 mM HEPES pH 7.4, 150 mM NaCl, 0.1% BSA, 0.05% Tween-20 for 2 hours at room temperature. The complex is captured on streptavidin-coated plates and detected with anti-BCL-2 antibody. IC50 is calculated from displacement curves.
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| Cell Assay |
Apoptosis assay: Hematological cancer cell lines (e.g., RS4;11, Jurkat, Ramos) are seeded in 96-well plates and treated with S65487 hydrochloride (0.01-1000 nM) for 24-72 hours. Apoptosis is measured by Annexin V-FITC/PI staining and flow cytometry, or by caspase-3/7 activity using a fluorogenic substrate (DEVD-Rhodamine). IC50 for apoptosis induction is calculated.
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| Animal Protocol |
Mouse xenograft model: Female NSG or SCID mice are implanted intravenously or subcutaneously with RS4;11 cells (5×10⁶). When tumors are established, mice receive a single intravenous injection of S65487 hydrochloride (10-50 mg/kg). Tumor burden is monitored by bioluminescence (if luciferase-labeled) or caliper measurements. Complete remission is assessed by survival and tumor-free status.
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| ADME/Pharmacokinetics |
Mouse PK following intravenous administration shows a half-life of approximately 2-4 hours, with moderate clearance and volume of distribution. The compound shows good tissue penetration and accumulates in tumors. Metabolism is primarily via CYP3A4-mediated oxidation. Oral bioavailability is limited (<10%) due to the large molecular weight (753.72).
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| Toxicity/Toxicokinetics |
In preclinical studies, S65487 hydrochloride is well-tolerated at therapeutic doses with no significant weight loss or organ toxicity. No hematological or biochemical abnormalities are reported at effective doses. At high doses (>100 mg/kg), mild gastrointestinal disturbances and lethargy may occur.
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| References | |
| Additional Infomation |
S65487 hydrochloride is a research compound, not FDA-approved. It is a potent BCL-2 inhibitor and the precursor of S55746, serving as a valuable tool for studying BCL-2 biology and evaluating BCL-2-targeted therapies. Its activity against BCL-2 mutations makes it useful for investigating resistance mechanisms in BCL-2-driven cancers.
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| Molecular Formula |
C41H41CLN6O4
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|---|---|
| Molecular Weight |
717.255048513412
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| Exact Mass |
752.264
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| CAS # |
1644543-95-2
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| Related CAS # |
S65487;1644600-79-2;S65487 sulfate;2416937-01-2
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| PubChem CID |
117831262
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
53
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| Complexity |
1300
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CC=C(C(=C1)C1=CC(C(N(C2C=CC(=CC=2)O)C2C=C(C#N)N(C)C=2C)=O)=C(C)N1C)C(N1CC2C=CC=CC=2C[C@H]1CN1CCOCC1)=O
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| InChi Key |
KBXPYZATHHDCAQ-WAQYZQTGSA-N
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| InChi Code |
InChI=1S/C41H41ClN6O4.ClH/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;1H/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;hydrochloride
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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 : 90 mg/mL (119.41 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.5 mg/mL (5.97 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 45.0 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: ≥ 4.5 mg/mL (5.97 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 45.0 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. View More
Solubility in Formulation 3: ≥ 4.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| 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.
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