MS5033
MS5033 is a CRBN-recruiting PROTAC degrader that targets AKT1. The IC50 values of MS5033 against human AKT range from 1.3 nM to 798 nM, with Kd values ranging from 4.8 nM to 160 nM. MS5033 inhibits downstream AKT signaling pathways, including the phosphorylation of PRAS40, thereby suppressing cancer cell proliferation and colony formation and inducing cancer cell apoptosis. MS5033 can be used in research on glioma, prostate cancer, triple-negative breast cancer, breast cancer and solid tumors.
(Pink: Akt ligand (HY-48682); Blue: Cereblon ligand (HY-10984); Black: linker (HY-133051)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- No. CAS: 2376137-29-8
- Fòrmula: C51H66ClN11O11
- Peso molecular:1044.59
-
Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
- Protocolo
- Pureza y Documentación
- Referencias
-
Help & FAQs
Ver todos los productos específicos de isoformas PROTACs
More
Actividad biológica
Descripciòn
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| PC-3 | DC50 |
430 nM
|
Concentration-dependent AKT degradation in human PC3 prostate cancer cells assessed via immunoblotting, with maximum degradation observed after 24 h incubation at 1 μM.
Concentration-dependent AKT degradation in human PC3 prostate cancer cells assessed via immunoblotting, with maximum degradation observed after 24 h incubation at 1 μM.
|
35119851 |
| PC-3 | GI50 |
10.8 μM
|
Antiproliferative activity against human PC3 prostate cancer cells assessed as reduction in cell confluence monitored over 3-5 days by live cell imaging.
Antiproliferative activity against human PC3 prostate cancer cells assessed as reduction in cell confluence monitored over 3-5 days by live cell imaging.
|
35119851 |
| MDA-MB-468 | GI50 |
4.8 μM
|
Antiproliferative activity against human MDA-MB-468 triple-negative breast cancer cells assessed as reduction in cell confluence monitored over 3-5 days by live cell imaging.
Antiproliferative activity against human MDA-MB-468 triple-negative breast cancer cells assessed as reduction in cell confluence monitored over 3-5 days by live cell imaging.
|
35119851 |
In Vitro
MS5033 (2 μM; 12 h) induces formation of the AKT-MS5033-CRBN ternary complex in E. coli-expressing HEK 293T cells, as measured by EGFP-based BiFC fluorescence[1].
MS5033 (2 μM; 12 h) induces formation of the AKT-MS5033-mutant CRBN ternary complex in mEAEC-expressing HEK 293T cells, as measured by EGFP-based BiFC fluorescence, without causing degradation of the reporter's AKT fusion protein[1].
MS5033 (2 μM; 24 h) induces degradation of the NLuc-AKT fusion protein in LALC-expressing HEK 293T cells, as measured by Western blotting, with residual protein levels at 0.45-fold of the DMSO control[1].
MS5033 (Compound 35) binds with high affinity to AKT1 and AKT3, and moderate affinity to AKT2 purified protein isoforms, with Kd values of 4.8 nM, 22 nM, and 160 nM, respectively[3].
MS5033 (Compound 62) inhibits purified AKT1, AKT2, and AKT3 kinases with IC50 values of 798 nM, 90 nM, and 544 nM, respectively[2].
MS5033 (30 nM-10 μM; 4-24 h) induces potent, time- and concentration-dependent, VHL- and ubiquitin-proteasome system-dependent AKT degradation in SW620 KRASG12C mutant colorectal cancer cells with a DC50 of 23 nM[2].
MS5033 (100 nM-1 μM) effectively induces AKT degradation in KRAS/BRAF mutant cancer cells (Colo205, HT-29, SKMEL 239, PANC-1) at 1 μM, with complete degradation in PANC-1 cells at 100 nM, and modest activity in Mia PaCa-2 cells[2].
MS5033 (1 μM; 18 h) acts as a selective AKT degrader in SW620 KRASG12D colorectal cancer cells, significantly reducing AKT1 and AKT2 protein levels with no substantial off-target degradation[2].
MS5033 effectively inhibits colony formation in PC3 PI3K/PTEN pathway mutant prostate cancer cells with potency comparable to related AKT PROTACs[2].
MS5033 (1-10 μM; 24 h) induces robust AKT degradation and downstream signaling inhibition in BT474 human breast cancer cells[3].
MS5033 (1 μM; 24 h) induces concentration-dependent AKT degradation in PC3 human prostate cancer cells with a DC50 of 430 nM, acting via a cereblon (CRBN)- and ubiquitin-proteasome system (UPS)-dependent mechanism, and reaches maximum degradation[3].
MS5033 (3-5 days) inhibits proliferation of PC3 human prostate cancer cells with a GI50 of 10.8 μM and MDA-MB-468 human triple-negative breast cancer cells with a GI50 of 4.8 μM[3].
MS5033 inhibits proliferation of SW620 KRASG12C mutant colorectal cancer cells with a GI50 of 3.1 μM, induces apoptosis, and suppresses colony formation, with activity dependent on AKT degradation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HEK 293T cells stably expressing wild-type luciferase-based AKT-PROTAC-Reporter (LALC: NLuc-AKT-P2A-CLuc-CRBN)
-
Concentration:2 μM
-
Incubation Time:24 h
-
Result:Reduced HA-LA (NLuc-AKT) protein levels to 0.45-fold of the DMSO control level, indicating degradation of the reporter's AKT fusion protein via the ubiquitin-proteasome pathway.
-
Cell Line:SW620 KRAS mutant colorectal cancer cells
-
Concentration:30 nM-10 μM (concentration-dependent AKT degradation); 1 μM (time-course analysis)
-
Incubation Time:4 h, 12 h, 24 h (time-course analysis)
-
Result:Induced potent, concentration-dependent total AKT degradation with a DC50 of 23 nM.
Achieved substantial total AKT depletion at 30 nM, near-complete degradation at 100 nM, with no hook effect observed up to 10 μM.
Induced significant AKT degradation at 4 h, near-complete degradation at 12 h, and sustained degradation for at least 24 h.
Rescued AKT degradation was observed with pretreatment of VHL-2, NEDD8-activating enzyme inhibitor, or proteasome inhibitor MG132.
Completely blocked AKT degradation was observed with pretreatment of AKT inhibitor ARQ-092.
-
Cell Line:BT474 human breast cancer cells
-
Concentration:1-10 μM
-
Incubation Time:24 h
-
Result:Reduced T-AKT protein levels significantly at 1 μM.
Inhibited phosphorylation of ribosomal protein S6 effectively.
Showed more potent activity than analogs with shorter PEG linkers, alkyl linkers, or modified CRBN binder moieties.
-
Cell Line:PC3 human prostate cancer cells
-
Concentration:1 μM; titration series (concentration-dependent degradation); pretreatments with 1 μM pomalidomide, 1 μM MLN4924, 20 μM MG-132, or 1 μM AZD5363
-
Incubation Time:8 h, 24 h (time-course analysis)
-
Result:Induced concentration-dependent total AKT degradation with a DC50 of 430 nM.
Achieved significant AKT downregulation at 8 h.
Reached maximum degradation at 24 h.
Diminished AKT-degrading activity was observed after pretreatment with pomalidomide, MLN4924, MG-132, or AZD5363.
-
Cell Line:PC3 human prostate cancer cells, MDA-MB-468 human triple-negative breast cancer cells
-
Concentration:titration series (GI50 measurement)
-
Incubation Time:3-5 days
-
Result:Inhibited PC3 cell growth with a GI50 of 10.8 μM.
Inhibited MDA-MB-468 cell growth with a GI50 of 4.8 μM.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | AUC |
|---|---|---|---|---|---|
| Mice[3] | 150 mg/kg | i.p. | 8 μM | 1 h | 32500 ng·h/mL |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Swiss Albino (male, 6 weeks old)[3]
-
Dosage:150 mg/kg
-
Administration:i.p.; single dose
-
Result:Achieved a maximum plasma concentration (Cₘₐₓ) of 8 μM at 1 h.
Reached an area under the curve (AUC) value of 32500 h·ng/mL.
Was well tolerated by mice with no reported toxicity.
- Western Blot
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Breast Cancer Modeling
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Apoptosis Solutions
- Protocol for Kinase activity and phosphorylation assays
- Soft Agar Colony Formation Assay
- MTT Cell Proliferation Assay
Chemical Information
-
No. CAS 2376137-29-8
-
Peso molecular 1044.59
-
Fòrmula C51H66ClN11O11
-
SMILES
O=C1C2=C(NCCOCCOCCOCCOCCOCCC(N3CCN(CC3)CC[C@@H](C4=CC=C(C=C4)Cl)NC(C5(CCN(C6=C7C(NC=C7)=NC=N6)CC5)N)=O)=O)C=CC=C2C(N1C8C(NC(CC8)=O)=O)=O
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[2]. Yu X, et al. Novel Allosteric Inhibitor-Derived AKT Proteolysis Targeting Chimeras (PROTACs) Enable Potent and Selective AKT Degradation in KRAS/BRAF Mutant Cells. Journal of medicinal chemistry. 2022 Oct 27;65(20):14237-14260. [Content Brief]
[3]. Yu X, et al. Discovery of Potent, Selective, and In Vivo Efficacious AKT Kinase Protein Degraders via Structure-Activity Relationship Studies. Journal of medicinal chemistry. 2022 Feb 24;65(4):3644-3666. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS5033 Related Classifications
HY-143882 Related Classifications
Powered by Bioz