| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| ln Vitro |
XMU-MP-8 (10 μM, 24 h) specifically produced a cell survival phenotype in the SKP2-FC cell line, while cell survival was not observed in other FC cell lines, which ruled out the possibility that it generally interfered with the activation of FC death proteins[1]. XMU-MP-8 (1-10 μM, 0-24 h) could trigger SKP2 ubiquitination and proteasome degradation, significantly shorten its half-life and consume endogenous SKP2 protein, but did not affect its mRNA level[1]. XMU-MP-8 (72 h) inhibited the proliferation of SKP2-overexpressing cancer cells, and its IC50 values against PC-3, A549, JHH-7, SW620, LoVo, RKO, Caco2 and HeLa cells were 3.7 μM, 6.7 μM, 3.7 μM, 6.2 μM, 4.5 μM, 6.9 μM, 5.6 μM and 5.3 μM, respectively[1]. XMU-MP-8 (10 μM, 72 h) completely blocked the proliferation of SKP2-overexpressing cell lines and induced massive cell death [1]. XMU-MP-8 (10 μM, 24 h) induced SKP2 protein degradation and p27 protein accumulation in SKP2-overexpressing cell lines (JHH-7 and PC-3), but did not cause significant changes in SKP2-low-expressing cell lines (IMR-90 and MCF-10A) [1]. XMU-MP-8 (2.5-10 μM, 0-5 days) had no significant effect on the growth of normal mouse intestinal organoids and human peripheral blood mononuclear cells [1]. XMU-MP-8 (10 μM, 2.5 h) recruits the E3 ligase STUB1 to the F-box domain of SKP2 to form a ternary complex, thereby enhancing the SKP2-STUB1 interaction by 122 times, ultimately leading to SKP2 ubiquitination and degradation [1].
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| ln Vivo |
XMU-MP-8 (15 and 30 mg/kg, intravenously, once daily for 14 days) demonstrated significant antitumor efficacy in A549 and PC-3 xenograft models by exacerbating SKP2 [1]. XMU-MP-8 (30 mg/kg, intravenously, once daily for 14 days) did not show adverse effects in BALB/c nude mice [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: JHH-7 and HeLa cells Tested Concentrations: 1, 2, 5, and 10 μM Incubation Duration: 0, 2, 4, 6, 8, 12 and 24 h Experimental Results: 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). Western Blot Analysis[1] Cell Types: A549 and PC-3 cells and derived genetically modified lines. Tested Concentrations: 5 and 10 μM Incubation Duration: 2.5 and 24 h Experimental Results: 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. |
| Animal Protocol |
Animal/Disease Models: Male BALB/c nude mice (6 weeks old)[1]
Doses: 30 mg/kg Route of Administration: i.v., daily for 14 days Experimental Results: 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. Animal/Disease Models: Male BALB/c nude mice (6 weeks old) subcutaneously injected with A549 or PC-3 cells[1] Doses: 15 and 30 mg/kg Route of Administration: i.v., daily for 14 days Experimental Results: 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. |
| References |
| Molecular Formula |
C26H21F3N8S
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|---|---|
| Molecular Weight |
534.56
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| CAS # |
2271314-01-1
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| Appearance |
White to off-white solid powder
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| Synonyms |
SKPer1
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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 : ~125 mg/mL (~233.84 mM; with sonication)
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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 | 1.8707 mL | 9.3535 mL | 18.7070 mL | |
| 5 mM | 0.3741 mL | 1.8707 mL | 3.7414 mL | |
| 10 mM | 0.1871 mL | 0.9353 mL | 1.8707 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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