| 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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Purity: =99.71%
S63845 is a potent, selective and high affinity small molecule inhibitor of MCL1 (myeloid cell leukemia 1) with Ki value < 1.2 nM. S63845 effectively kills MCL1-dependent cancer cells, such as multiple myeloma, leukemia, and lymphoma cells, by triggering the mitochondrial apoptotic pathway. As a single agent, S63845 exhibits in vivo significant anti-tumor activity in a number of cancers with a tolerable safety margin. MCL1 inhibition also demonstrated efficacy against a number of stable cancer-derived cell lines, either alone or in combination with other anti-cancer medications. These findings suggest MCL1 as a target for the treatment of a variety of tumors. It acts by binding to the BH3-binding groove of MCL-1 with a KD value of 0.19 nM for human MCL-1. It is the first high affinity MCL-1 inhibitor with potent in vivo activity. S63845 is also very selective against other BCL family proteins like BCL-2 (Ki >10,000nM) and BCL-XL (Ki >10,000nM). Multiple myeloma, leukemia, and lymphoma cells were among the cancer cells that S63845 demonstrated had clear-on-target activity killing. It demonstrated effective in vivo antitumor activity with a favorable safety profile when used as monotherapy to treat various cancer types.
| Targets |
MCL1 (Kd = 0.19 nM)
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| ln Vitro |
S63845 induces death of cancer cell lines with known reliance on MCL-1, which also causes the mitochondrial outer membrane to permeabilize and display the traditional signs of apoptosis. It is 6 times more affine for human MCL-1 than for mouse MCL-1[1]. S63845 is efficient against haematological cancer-derived cell lines in vitro and in vivo, as well as AML samples, but it is not very effective against healthy 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 |
As a running buffer, 10 mM HEPES pH 7.4, 175 mM NaCl, 25 μM EDTA, 1 mM TCEP, 0.01% P20 and 1% DMSO. Using proteins with two His tags, the ligand surface is produced. The substance is applied to the protein surface after being diluted in buffer in steps. With injection times of 120 seconds and dissociation times of 360 seconds, all sample measurements are carried out at a flow rate of 30 μL per minute. Injections of 0.35 M EDTA pH 8.0, 0.1 mg/mL trypsin, 0.5 M imidazole, and 45% DMSO over a 60 second period at a rate of 15 μL per minute are used to repeatedly regenerate the sensor surface.
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| Cell Assay |
HeLa cells transduced with Flag–BCL-XL, Flag–BCL-2 or Flag–MCL1 expression constructs are treated for 4 h with increasing concentrations of S63845, before immunopreciptation using anti-FLAG antibody. Immunoblotting is used to look for FLAG-tagged proteins as well as the related BAK and BAX proteins in immunoprecipitates and total inputs.
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| Animal Protocol |
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| References |
| Molecular Formula |
C39H37CLF4N6O6S
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|---|---|
| Molecular Weight |
829.26
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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 |
S-63845; S 63845; S63845
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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) |
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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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