| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
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Purity: ≥98%
S63845 TFA, the Trifluoroacetic acid salt of S63845, is a potent, selective small molecule inhibitor of MCL1 (myeloid cell leukemia 1). The Ki value for Ki value < 1.2 nM. By triggering the BAX/BAK-dependent mitochondrial apoptotic pathway, S63845 effectively kills MCL1-dependent cancer cells, such as multiple myeloma, leukemia, and lymphoma cells. In vivo, S63845 exhibits strong anti-tumor activity in a number of cancers with a tolerable safety margin. Additionally, MCL1 inhibition, either by itself or in conjunction with other anti-cancer medications, was successful against a number of reliable cancer-derived cell lines.
| Targets |
Mcl-1 (Kd = 0.19 nM)
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| ln Vitro |
S63845 induces death of cancer cell lines with known reliance on MCL-1, displaying classical hallmarks of apoptosis that are dependent on caspases and BAX/BAK-mediated mitochondrial outer membrane permeabilisation. Compared to mouse MCL-1, it has a 6 fold higher affinity for human MCL-1[1]. S63845 is effective in vitro, in vivo, and on AML samples as well as haematological cancer-derived cell lines, but it is not very effective on normal human haematopoietic progenitor cells[2].
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| ln Vivo |
In vivo, S63845 exhibits strong anti-tumor activity in a number of cancers with a tolerable safety margin. The mice tolerate S63845 well, and no discernible weight loss was seen. Some solid tumor models respond well to S63845 monotherapy, but many others only respond to the combination of S63845 and oncogenic kinase inhibitors[2].
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| Enzyme Assay |
Running buffer is composed of 10 mM HEPES pH 7.4, 175 mM NaCl, 25 μM EDTA, 1 mM TCEP, 0.01% P20, and 1% DMSO. Proteins that have been double His-tagged are used to create the ligand surface. The compound is diluted serially in buffer and injected onto the protein surface. The flow rate used for all sample measurements is 30 μL per minute (injection time: 120 s, dissociation time: 360 s). By repeatedly injecting 0.35 M EDTA pH 8.0 with 0.1 mg/mL trypsin, 0.5 M imidazole, and 45% DMSO (60 s, 15 μL per min), the sensor surface is restored.
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| Cell Assay |
Before using anti-FLAG antibody for immunoprecipitation, HeLa cells transduced with Flag-BCL-XL, Flag-BCL-2, or Flag-MCL1 expression constructs are treated for 4 hours with increasing concentrations of S63845. Immunoblotting is used to examine immunoprecipitates and total inputs for FLAG-tagged proteins as well as the related BAK and BAX proteins.
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| Animal Protocol |
Human multiple myeloma (H929 and AMO1) xenografted mice; Intravenously injected (i.v.), 25 mg/kg
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| References |
| Molecular Formula |
C39H37CLF4N6O6S
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|---|---|
| Molecular Weight |
829.2593
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| Exact Mass |
828.212
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| Elemental Analysis |
C, 56.49; H, 4.50; Cl, 4.27; F, 9.16; N, 10.13; O, 11.58; S, 3.87
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| CAS # |
1799633-27-4
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| Related CAS # |
(S,R)-S63845;(R,R)-S63845
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| Appearance |
White to off-white solid powder
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| SMILES |
CC1=C(C=CC(=C1Cl)OCCN2CCN(CC2)C)C3=C(SC4=NC=NC(=C34)O[C@H](CC5=CC=CC=C5OCC6=CC=NN6CC(F)(F)F)C(=O)O)C7=CC=C(O7)F
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| InChi Key |
ZFBHXVOCZBPADE-SSEXGKCCSA-N
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| InChi Code |
InChI=1S/C39H37ClF4N6O6S/c1-23-26(7-8-28(34(23)40)53-18-17-49-15-13-48(2)14-16-49)32-33-36(45-22-46-37(33)57-35(32)29-9-10-31(41)55-29)56-30(38(51)52)19-24-5-3-4-6-27(24)54-20-25-11-12-47-50(25)21-39(42,43)44/h3-12,22,30H,13-21H2,1-2H3,(H,51,52)/t30-/m1/s1
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| Chemical Name |
(2R)-2-[5-[3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[[2-(2,2,2-trifluoroethyl)pyrazol-3-yl]methoxy]phenyl]propanoic acid
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| Synonyms |
S63845 Trifluoroacetic acid; S-63845 TFA; S 63845
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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)
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| Solubility (In Vitro) |
DMSO: >41.45mg/mL
Water: >10mg/mL Methanol: >20mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.51 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 20.8 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: ≥ 2.08 mg/mL (2.51 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 20.8 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: 5 mg/mL (6.03 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2059 mL | 6.0295 mL | 12.0589 mL | |
| 5 mM | 0.2412 mL | 1.2059 mL | 2.4118 mL | |
| 10 mM | 0.1206 mL | 0.6029 mL | 1.2059 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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