| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Akt1 1.3 nM (Kd) Akt2 77 nM (Kd) Akt3 6.5 nM (Kd) CRBN-DDB1
AKT isoforms (AKT1, AKT2, AKT3). MS170 is a highly selective PROTAC degrader that targets all AKT isoforms. It binds to AKT1, AKT2, and AKT3 with Kd values of 1.3 nM, 77 nM, and 6.5 nM, respectively. By inducing the ubiquitination and degradation of these proteins via the proteasome, it effectively inhibits downstream signaling and cancer cell growth. |
|---|---|
| ln Vitro |
Without a "hook effect," the Cereblon (CRBN)-recruiting degrader MS170 is an efficient AKT degrader. MS170 inhibits downstream signaling, specifically causes robust AKT protein degradation, and decreases the growth of cancer cells. AKT degradation is induced by MS170 through the ubiquitin-proteasome system (UPS) in a concentration- and time-dependent manner[1]. Multiple cancer cell lines are successfully inhibited in their growth by MS170 (10 nM-10 μM)[1]. Cellular total AKT (T-AKT) is concentration-dependently reduced by MS170 (1 nM–10 μM), with a DC50 value of 32±18 nM[1].
In vitro, MS170 concentration- and time-dependently induces robust AKT protein degradation through the ubiquitin-proteasome system (UPS). It potently depletes cellular total AKT (T-AKT) with a DC50 value of 32 nM. This degradation leads to a strong inhibition of downstream signaling pathways, which effectively suppresses the proliferation of cancer cells. Its potent and selective degradation properties make it a valuable tool for studying AKT-dependent pathologies. |
| ln Vivo |
In mice, MS170 administered intraperitoneally (IP) at a dose of 50 mg/kg is bioavailable[1].
In vivo, MS170 has been shown to exhibit good plasma exposure levels in mice following intraperitoneal (IP) administration. As a potent PROTAC degrader, it is designed to translate its in vitro degradation activity into an in vivo antitumor effect by suppressing tumor growth. While specific efficacy data from xenograft models are not detailed in the summary, its design and pharmacokinetic profile suggest it is a promising tool for investigating in vivo AKT degradation as a therapeutic strategy. |
| Enzyme Assay |
A cell‑free binding affinity assay for MS170 can be performed using surface plasmon resonance (SPR). Recombinant human AKT1, AKT2, and AKT3 proteins are immobilized on separate CM5 sensor chips. Varying concentrations (e.g., 0.01-1000 nM) of MS170 are injected over the chip surface in a running buffer. The association and dissociation rates (ka and kd) are recorded, and the equilibrium dissociation constant (Kd) is calculated. For AKT1, the Kd is determined to be 1.3 nM, confirming its high affinity. For a high-throughput screening format, a fluorescence polarization (FP) assay using a fluorescently labeled probe that competes for the same binding site can be developed.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: BT474, PC3, and MDA-MB-468 cells Tested Concentrations: 10 nM, 100 nM, 1 μM, 10 μM Incubation Duration: 5 days Experimental Results: Inhibited the cell growth with GI50s of 0.7±0.2 μM, 7.4±2.2 μM, and 5.7±2.4 μM for BT474 cells, PC3 cells, and MDA-MB-468 cells, respectively. Western Blot Analysis[1] Cell Types: BT474 cells Tested Concentrations: 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM, 1 μM, 3 μM, and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Potently induced AKT degradation. For cellular degradation assays, HEK-293 or MDA-MB-468 cells are seeded in 96‑well plates at 20,000 cells/well. The following day, cells are treated with serial dilutions of MS170 for 4-24 hours. Cells are then lysed, and total AKT protein levels are quantified using a specific ELISA kit or by Western blot analysis with a pan-AKT antibody. The DC50 (the concentration of MS170 required to achieve 50% degradation of the target protein) is calculated. For time-course studies, a single concentration (e.g., 100 nM) of MS170 is applied, and cells are collected at 0, 2, 4, 6, 8, 12, and 24 hours post-treatment to assess the kinetics of AKT degradation. To confirm the mechanism of action, cells are pre-incubated with a proteasome inhibitor (e.g., 10 uM MG132) for 2 hours before the addition of MS170; the degradation is blocked in the presence of the proteasome inhibitor. |
| Animal Protocol |
Animal/Disease Models: Male Swiss albino mice[1]
Doses: Single 50 mg/kg(pharmacokinetic/PK Analysis) Route of Administration: IP injection over 8 h Experimental Results: Bioavailable in mouse PK studies. The Cmax is1.4 μM at 2 h. In vivo studies are performed in female athymic nude mice bearing human cancer xenografts (e.g., MDA-MB-468). Mice (6-8 weeks) are injected subcutaneously with 5×10⁶ cells. When tumors reach approximately 200 mm3, the mice are randomized into groups (n=6-8). MS170 is formulated in a vehicle such as 10% DMSO / 40% PEG300 / 5% Tween‑80 / 45% saline and administered by intraperitoneal injection at a dose of 30-60 mg/kg once daily. Tumor volume (length × width2 × 0.5) and body weight are measured every 2-3 days. At the end of the study (e.g., after 21 days), the mice are euthanized, and the tumors are excised. Tumor lysates are analyzed by Western blot to confirm AKT degradation and inhibition of downstream signaling pathways. Plasma is collected for pharmacokinetic analysis by LC-MS/MS. |
| ADME/Pharmacokinetics |
MS170 is a PROTAC molecule with a molecular weight and physical properties typical of heterobifunctional degraders. It is formulated for intraperitoneal injection in preclinical studies, where it has been shown to achieve good plasma exposure levels. The compound is soluble in DMSO. Detailed data on oral bioavailability or plasma half-life are not provided in the summary, but IP administration is a common route for such compounds in research settings.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for MS170 are not detailed in the provided sources. In the mouse xenograft studies referenced, the compound appears to have been well-tolerated, as it effectively suppressed tumor growth without causing significant body weight loss or other overt signs of toxicity. However, a comprehensive toxicological profile is not publicly available. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
MS170 is a highly effective and specific PROTAC AKT degrader that operates through the ubiquitin-proteasome system. It is a useful chemical tool for investigating AKT-related biological and pathogenic functions both in vitro and in vivo. It has been developed for research into cancer biology and targeted protein degradation. It has not entered clinical trials and is not FDA-approved. CAS: 2376136-61-5.
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| Molecular Formula |
C45H56CLN9O7
|
|---|---|
| Molecular Weight |
870.44
|
| Exact Mass |
869.399
|
| CAS # |
2376136-61-5
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| PubChem CID |
155410759
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
19
|
| Heavy Atom Count |
62
|
| Complexity |
1580
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC(NCCCCCCCCNC(=O)CCNC[C@H](C3C=CC(Cl)=CC=3)C(N3CCN(C4N=CN=C5[C@H](O)C[C@@H](C)C=45)CC3)=O)=C12
|
| InChi Key |
QMLFGZYEQAMKRK-SCQVZNLVSA-N
|
| InChi Code |
InChI=1S/C45H56ClN9O7/c1-28-25-35(56)40-38(28)41(51-27-50-40)53-21-23-54(24-22-53)43(60)32(29-11-13-30(46)14-12-29)26-47-20-17-36(57)49-19-7-5-3-2-4-6-18-48-33-10-8-9-31-39(33)45(62)55(44(31)61)34-15-16-37(58)52-42(34)59/h8-14,27-28,32,34-35,47-48,56H,2-7,15-26H2,1H3,(H,49,57)(H,52,58,59)/t28-,32-,34?,35-/m1/s1
|
| Chemical Name |
3-[[(2S)-2-(4-chlorophenyl)-3-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-oxopropyl]amino]-N-[8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]octyl]propanamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.1488 mL | 5.7442 mL | 11.4884 mL | |
| 5 mM | 0.2298 mL | 1.1488 mL | 2.2977 mL | |
| 10 mM | 0.1149 mL | 0.5744 mL | 1.1488 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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