| 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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| Other Sizes |
| Targets |
VPS4B ( IC50 = 0.71 μM ); p97 ( IC50 = 7.2 μM )
The primary targets of MSC1094308 are VCP/p97 (a type II AAA ATPase) and VPS4B (a type I AAA ATPase). It binds to a previously characterized druggable hotspot of p97, inhibiting its D2 ATPase activity. AAA ATPases play critical roles in various cellular processes, including protein degradation, membrane fusion, and DNA replication. |
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| ln Vitro |
In HCT116 cells, polyubiquitin accumulation is induced by MSC1094308 (10 μM; 8 hours) as a biomarker of homeostatic inhibition [1].
In vitro, MSC1094308 is a non-competitive and reversible allosteric inhibitor of VPS4B and p97. It inhibits D2 ATPase activity by binding to the druggable hotspot of p97. Its activity is measured by ATPase assays. It can be used in studies of cancer, as AAA ATPases are involved in protein degradation pathways critical for cancer cell survival. |
| ln Vivo |
In vivo efficacy data for MSC1094308 are not extensively detailed. As an inhibitor of AAA ATPases, it has potential for treating cancers that are dependent on these proteins. However, specific in vivo studies with this compound have not been widely reported. It is intended for research use only.
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| Enzyme Assay |
For ATPase assays, the enzymatic activity of recombinant p97 or VPS4B is measured. The enzyme is incubated with varying concentrations of MSC1094308 in a reaction buffer containing ATP. The reaction is monitored by measuring the release of inorganic phosphate or by using a coupled enzyme assay. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCT116 cells Tested Concentrations: 10 µM Incubation Duration: 8 h Experimental Results: Resulting in the accumulation of polyubiquitinated proteins (biomarkers of degradation inhibition). For cellular studies, cancer cells are cultured in appropriate medium. MSC1094308 is dissolved in DMSO and diluted in culture medium. Cells are treated with the compound. Cell viability is assessed by MTT or CellTiter-Glo assays. The levels of ubiquitinated proteins and other markers of proteasomal function are analyzed by Western blot. |
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are implanted with cancer cells. MSC1094308 is formulated in vehicle and administered intraperitoneally or intravenously. Tumor growth is monitored. At study termination, tumors are excised and processed for analysis of ATPase activity, ubiquitinated protein levels, and proliferation markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for MSC1094308 are not extensively reported. As a small molecule, it is expected to have moderate oral bioavailability. Its metabolism likely involves hepatic CYP450 enzymes. A comprehensive PK study would be needed to determine its half-life, Cmax, and AUC for any potential therapeutic development.
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| Toxicity/Toxicokinetics |
Toxicological data for MSC1094308 are limited. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
MSC1094308 (CAS 2219320-08-6) is a reversible allosteric inhibitor of VCP/p97 and VPS4B. It has IC50 values of 0.71 μM and 7.2 μM for VPS4B and p97, respectively. It has the molecular formula C₂₉H₂₉F₃N₂ and a molecular weight of 462.55. It is used in cancer research and is strictly for research use.
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| Molecular Formula |
C29H29F3N2
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|---|---|
| Molecular Weight |
462.549177885056
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| Exact Mass |
462.23
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| Elemental Analysis |
C, 75.30; H, 6.32; F, 12.32; N, 6.06
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| CAS # |
2219320-08-6
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| PubChem CID |
139035043
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| Appearance |
Off-white to pink solid powder
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| LogP |
7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
595
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC2=C(CC1CNCCCC(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F)C5=C(N2)C=CC(=C5)F
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| InChi Key |
OCZIMUMAPGQEBH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H29F3N2/c30-22-8-4-20(5-9-22)25(21-6-10-23(31)11-7-21)2-1-15-33-18-19-3-13-28-26(16-19)27-17-24(32)12-14-29(27)34-28/h4-12,14,17,19,25,33-34H,1-3,13,15-16,18H2
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| Chemical Name |
4,4-bis(4-fluorophenyl)-N-[(6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methyl]butan-1-amine
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| Synonyms |
MSC-1094308; MSC1094308; MSC 1094308
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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 |
| 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: ~50 mg/mL (~108.1 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.40 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 25.0 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: ≥ 2.5 mg/mL (5.40 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 25.0 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: ≥ 2.5 mg/mL (5.40 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 | 2.1619 mL | 10.8096 mL | 21.6193 mL | |
| 5 mM | 0.4324 mL | 2.1619 mL | 4.3239 mL | |
| 10 mM | 0.2162 mL | 1.0810 mL | 2.1619 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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