| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
798 nM (AKT-1), 90 nM (AKT-2), 544 nM (AKT-3)[1]
MS15 TFA targets AKT1, AKT2, and AKT3 via a PROTAC mechanism. It consists of an allosteric inhibitor warhead that binds to AKT and a recruiter for an E3 ubiquitin ligase, leading to ubiquitination and subsequent proteasomal degradation of AKT proteins. It is selective for AKT over other kinases. |
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| ln Vitro |
MS15 (0-10 μM, 24-hour period) In both MS21-resistant KRAS/BRAF mutant cells and SW620 cells, TFA can efficiently cause AKT degradation [1]. MS15 at 0–10 μM for five days KRAS mutant SW620 cell growth is inhibited by TFA [1]. AKT degradation is mediated in a time- and UPS-dependent manner by MS15 (1 μM, 1-24 hours) TFA [1].
MS15 TFA inhibits AKT1, AKT2, and AKT3 activities with IC50 values of 798 nM, 90 nM, and 544 nM, respectively. It induces nearly complete AKT degradation at concentrations as low as 100 nM in SW620 colorectal cancer cells and PANC-1 pancreatic cancer cells. At 1 microM, it induces AKT degradation in BRAF mutant cell lines including Colo205, HT-29, and SKMEL-239 cells. |
| ln Vivo |
MS15 administered intraperitoneally (i.p., once at a dose of 75 mg/kg) is bioavailable in mice [1].
MS15 (75 mg/kg, intraperitoneal, once) is bioavailable in mice. The compound can be used to study the effects of AKT degradation on tumor growth, survival signaling, and drug resistance. Specific in vivo efficacy data in xenograft models is not provided but AKT degradation is expected to suppress PI3K/AKT-driven tumor growth. |
| Enzyme Assay |
A standard in vitro AKT kinase inhibition assay involves incubating recombinant AKT1, AKT2, or AKT3 (1-10 nM) with a peptide substrate (e.g., Crosstide: GRPRTSSFAEG) and ATP (10-100 microM) in kinase buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM DTT) with varying concentrations of MS15 TFA (0.1-10,000 nM) for 30-60 minutes at 30degC. Kinase activity is measured using a luminescent ADP detection kit (ADP-Glo) or by 33P-ATP incorporation. IC50 values (90 nM for AKT2, 544 nM for AKT3, 798 nM for AKT1) are calculated.
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| Cell Assay |
A standard cellular protocol for assessing AKT degradation involves treating KRAS/BRAF mutant cancer cells (e.g., SW620, PANC-1, Colo205, HT-29, SKMEL-239) with MS15 TFA at varying concentrations (0.01-10 microM) for 4-24 hours. Cells are lysed and analyzed by Western blotting using anti-AKT1/2/3 and anti-tubulin (loading control) antibodies. Near-complete AKT degradation at 100 nM in SW620 and PANC-1 cells is observed. To validate the degradation mechanism, cells are co-treated with the proteasome inhibitor MG-132 (10 microM).
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| Animal Protocol |
A standard in vivo protocol involves administering MS15 TFA to mice by intraperitoneal injection (75 mg/kg, once). Blood and tissue samples (e.g., tumor xenografts, liver) are collected at various time points (1-24 hours post-dose). Plasma and tissue homogenates are analyzed by LC-MS to quantify MS15 concentrations, and AKT protein levels in tissues are measured by Western blotting to assess target degradation.
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| ADME/Pharmacokinetics |
MS15 TFA has a molecular weight of 1228.47 (C66H80F3N11O7S). It is soluble in DMSO at ≥100 mg/mL (81.40 mM). For intraperitoneal administration in mice, it can be formulated in co-solvent systems such as 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. It is bioavailable (75 mg/kg, IP, once) in mice. The compound should be stored at -80degC, protected from light, and under nitrogen.
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| Toxicity/Toxicokinetics |
No specific toxicological data for MS15 TFA is available. As a selective AKT degrader, its toxicity would be related to AKT pathway inhibition, which can affect cell survival, metabolism, and glucose homeostasis. Potential on-target toxicities include hyperglycemia, metabolic dysregulation, and immunosuppression. However, comprehensive safety studies have not been published for this research compound.
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| References | |
| Additional Infomation |
MS15 TFA is a research-grade PROTAC AKT degrader. It is derived from an allosteric AKT inhibitor and represents a novel approach to targeting the PI3K/AKT pathway through protein degradation rather than kinase inhibition. This strategy may overcome resistance mechanisms associated with AKT inhibitors. It has not been approved for clinical use and is strictly for laboratory research in cancer biology and drug resistance studies.
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| Molecular Formula |
C66H80F3N11O7S
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|---|---|
| Molecular Weight |
1228.47
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| Related CAS # |
MS15
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| Appearance |
White to yellow solid powder
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :≥ 100 mg/mL (~81.40 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8140 mL | 4.0701 mL | 8.1402 mL | |
| 5 mM | 0.1628 mL | 0.8140 mL | 1.6280 mL | |
| 10 mM | 0.0814 mL | 0.4070 mL | 0.8140 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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