XMU-MP-8
Based on 1 Customer Validation
XMU-MP-8 (SKPer1) is a potent molecular glue degrader that targets the oncoprotein SKP2. XMU-MP-8 simultaneously binds to the F-box domain of SKP2 (Kd ≈ 36 μM) and the N-terminal TPR domain of the E3 ligase STUB1 (Kd ≈ 2.5 μM), forming a stable SKP2-SKPer1-STUB1 ternary complex (Kd ≈ 8.9 nM) that induces SKP2 ubiquitination and proteasomal degradation. XMU-MP-8 selectively eliminates SKP2-expressing cancer cells. XMU-MP-8 exhibits substantial tumour suppression with good safety profiles in vivo. XMU-MP-8 can be used for cancer research, such as non-small cell lung adenocarcinoma (NSCLC) and prostatic adenocarcinoma.
For research use only. We do not sell to patients.
- Purity: 99.23%
- CAS No.: 2271314-01-1
- Formula: C26H21F3N8S
- Molecular Weight:534.56
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Metabolism/Protease Compound Library
HY-L012
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Anti-Cancer Compound Library
HY-L025
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Oxygen Sensing Compound Library
HY-L045
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Ubiquitination Compound Library
HY-L050
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Anti-Lung Cancer Compound Library
HY-L075
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Molecular Glue Compound Library
HY-L137
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Metabolic Enzyme Compound Library
HY-L146
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Mitophagy Compound Library
HY-L180
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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Amino Acid Metabolism Compound Library
HY-L189
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Cell Proliferation Compound Library
HY-L201
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High-Throughput Bioactive Compound Library
HY-L205
Biological Activity
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SKP2 36 μM (Kd) |
XMU-MP-8 (10 μM, 24 h) produces a cell survival phenotype specifically in the SKP2-F-C cell line, with no survival observed in other F-C cell lines, ruling out the possibility that it generally interferes with the activation of the F-C death protein[1].
XMU-MP-8 (1-10 μM, 0-24 h) triggers SKP2 ubiquitination and proteasomal degradation, significantly reducing its half-life and depleting endogenous SKP2 protein without affecting its mRNA levels[1].
XMU-MP-8 (72 h) inhibits proliferation of SKP2-high cell lines with IC50s of 3.7 μM (PC-3), 6.7 μM (A549), 3.7 μM (JHH-7), 6.2 μM (SW620), 4.5 μM (LoVo), 6.9 μM (RKO), 5.6 μM (Caco2) and 5.3 μM (HeLa)[1].
XMU-MP-8 (10 μM ,72 h) completely blocks proliferation and induces massive cell death of SKP2-high cell lines[1].
XMU-MP-8 (10 μM, 24 h) induces the degradation of SKP2 protein and the accumulation of p27 protein in SKP2-high cell lines (JHH-7 and PC-3), with no significant changes in SKP2-low cell lines (IMR-90 and MCF-10A)[1].
XMU-MP-8 (2.5-10 μM, 0-5 days) shows no significant effect on the growth of normal mouse intestine organoids and human peripheral blood mononuclear cells[1].
XMU-MP-8 (10 μM ,2.5 h) induces SKP2 degradation by recruiting the E3 ligase STUB1 to the F-box domain of SKP2, forming a ternary complex that enhances the SKP2-STUB1 interaction by 122-fold and ultimately leads to SKP2 ubiquitination and degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:JHH-7 and HeLa cells
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Concentration:1, 2, 5, and 10 μM
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Incubation Time:0, 2, 4, 6, 8, 12 and 24 h
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Result:Reduced SKP2 levels in JHH-7 and HeLa cells in a dose- and time-dependent manner.
Degraded SKP2 through the proteasome, but not the lysosome.
Induced ubiquitination of SKP2.
Significantly reduced the SKP2 half-life of SKP2 (from 10.8 h to 3.3 h in JHH-7 cells, and from 11.3 h to 6.2 h in HeLa cells).
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Cell Line:A549 and PC-3 cells and derived genetically modified lines.
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Concentration:5 and 10 μM
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Incubation Time:2.5 and 24 h
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Result:Failed to degrade SKP2-F-C when three lysine residues (3K>R) in its F-box domain were mutated.
Failed to induce ubiquitination of the SKP2 3K>R mutant protein.
Was unable to exert its anti-proliferative effect in cells where endogenous SKP2 had been replaced with the degradation-resistant 3K>R mutant.
Failed to induce SKP2 ubiquitination and degradation in STUB1 knockout cells.
Re-gained its ability to degrade SKP2 following the reconstitution of sgRNA-resistant STUB1 in STUB1 knockout cells.
Still recruited the 3K>R mutant to STUB1, even though this mutant was resistant to degradation.
XMU-MP-8 (30 mg/kg, i.v., daily for 14 days) shows no adverse effects in BALB/c nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male BALB/c nude mice (6 weeks old)[1]
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Dosage:30 mg/kg
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Administration:i.v., daily for 14 days
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Result:Exhibited no significant changes in body weight and liver function (ALT/AST levels).
Showed no histopathological damage in the heart, kidney, liver, lung, or spleen.
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Animal Model:Male BALB/c nude mice (6 weeks old) subcutaneously injected with A549 or PC-3 cells[1]
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Dosage:15 and 30 mg/kg
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Administration:i.v., daily for 14 days
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Result:Completely ceased the growth of A549 tumors.
Caused a 95 % reduction in tumour growth in PC-3 xenograft model.
Caused depletion of SKP2 and an increase of p27 in the xenograft PC-3 tumour.
Chemical Information
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CAS No. 2271314-01-1
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Appearance Solid
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Molecular Weight 534.56
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Formula C26H21F3N8S
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Color White to off-white
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SMILES
CN1N=CC2=C(NCC3=CC=CN=C3)N=C(C4=CC=CC(NC(NC5=CC=CC(C(F)(F)F)=C5)=S)=C4)N=C21
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Synonyms
SKPer1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 116.67 mg/mL (218.25 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.8707 mL | 9.3535 mL | 18.7070 mL | 46.7674 mL |
| 5 mM | 0.3741 mL | 1.8707 mL | 3.7414 mL | 9.3535 mL | |
| 10 mM | 0.1871 mL | 0.9353 mL | 1.8707 mL | 4.6767 mL | |
| 15 mM | 0.1247 mL | 0.6236 mL | 1.2471 mL | 3.1178 mL | |
| 20 mM | 0.0935 mL | 0.4677 mL | 0.9353 mL | 2.3384 mL | |
| 25 mM | 0.0748 mL | 0.3741 mL | 0.7483 mL | 1.8707 mL | |
| 30 mM | 0.0624 mL | 0.3118 mL | 0.6236 mL | 1.5589 mL | |
| 40 mM | 0.0468 mL | 0.2338 mL | 0.4677 mL | 1.1692 mL | |
| 50 mM | 0.0374 mL | 0.1871 mL | 0.3741 mL | 0.9353 mL | |
| 60 mM | 0.0312 mL | 0.1559 mL | 0.3118 mL | 0.7795 mL | |
| 80 mM | 0.0234 mL | 0.1169 mL | 0.2338 mL | 0.5846 mL | |
| 100 mM | 0.0187 mL | 0.0935 mL | 0.1871 mL | 0.4677 mL |
XMU-MP-8 Related Classifications
HY-W1128879 Related Classifications
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