SZL P1-41
目录号 : GC11869
SZL P1-41是一种特异性S期激酶相关蛋白2（Skp2）抑制剂。
Cas No.:222716-34-9
Sample solution is provided at 25 µL, 10mM.
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SZL P1-41 is a specific inhibitor of S phase kinase-associated protein 2 (Skp2)[1]. SZL P1-41 can prevent the assembly of Skp2-Skp1 complex and inhibit Skp2-mediated p27Kip1 and Akt ubiquitination[2]. SZL P1-41 has tumor growth inhibitory activity and has therapeutic effects on pulmonary fibrosis[3].
In vitro, SZL P1-41 (0-20μM) treatment of prostate cancer cell lines (PC-3 and LNCaP cells) for 3 days reduced the viability of cancer cells in a concentration-dependent manner, but had little effect on the viability of normal prostate epithelial PNT1A cells, and also induced the expression of endogenous p27 and p21 proteins in PC-3 cells[4]. SZL P1-41 (20μM) treatment of A549 and H1299 cells for 24 h significantly induced the expression of p27 protein[5].
In vivo, SZL P1-41 (80 mg/kg) was treated by intraperitoneal injection for 28 days in mice with renal cancer, which significantly inhibited tumor growth (reduced Ki-67, increased p21), induced cell apoptosis (increased C-Cas-3), and showed synergistic therapeutic effects when used in combination with MLN8237[6]. SZL P1-41 (80 mg/kg) was treated by intraperitoneal injection for 14 days in mice with bleomycin-induced pulmonary fibrosis, which significantly reduced the expression of COL1A1 and fibronectin in the lungs, attenuated the progression of pulmonary fibrosis, and restored body weight[7].
References:
[1] Jing J, Rui L, Junyuan S, et al. Small-molecule compounds inhibiting S-phase kinase-associated protein 2: a review[J]. Frontiers in Pharmacology, 2023, 14: 1122008.
[2]Wu J, Su H, Yu Z, et al. Skp2 modulates proliferation, senescence and tumorigenesis of glioma[J]. Cancer Cell International, 2020, 20: 1-11.
[3]Chuang H M, Shih T E, Lu K Y, et al. Mesenchymal stem cell therapy of pulmonary fibrosis: improvement with target combination[J]. Cell Transplantation, 2018, 27(11): 1581-1587.
[4]Chan C H, Morrow J K, Li C F, et al. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression[J]. Cell, 2013, 154(3): 556-568.
[5]Zhang S B, Hong M, Sun X Y, et al. Silybin has therapeutic efficacy against non-small cell lung cancer through targeting of skp2[J]. Acta Materia Medica, 2022, 1(3): 302-313.
[6]Li P, Chen T, Kuang P, et al. Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality[J]. Cell Death & Disease, 2022, 13(7): 606.
[7]Mikamo M, Kitagawa K, Sakai S, et al. Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis[J]. International journal of molecular sciences, 2018, 19(2): 474.
SZL P1-41是一种特异性S期激酶相关蛋白2（Skp2）抑制剂[1]。 SZL P1-41可阻止Skp2-Skp1复合物的组装，并抑制Skp2介导的p27 Kip1和Akt泛素化[2]。SZL P1-41具有肿瘤生长抑制活性，还有治疗肺纤维化的作用[3]。
在体外，SZL P1-41（0-20μM）处理前列腺癌细胞系（PC-3和LNCaP细胞）3 天，浓度依赖性地降低了癌细胞的活力，但对正常前列腺上皮PNT1A细胞的活力影响较小，还诱导了PC-3细胞中内源性p27和p21蛋白的表达[4]。SZL P1-41（20μM）处理A549和H1299细胞24 h，显著诱导了p27蛋白的表达[5]。
在体内，SZL P1-41（80 mg/kg）通过腹膜内注射治疗肾癌小鼠28天，显著抑制了肿瘤生长（Ki-67降低、p21升高），诱导了细胞凋亡（增加C-Cas-3），并与MLN8237联合使用表现出协同治疗作用[6]。SZL P1-41（80 mg/kg）通过腹膜内注射治疗博莱霉素诱导的肺纤维化小鼠14天，显著减少了肺的COL1A1和纤连蛋白的表达，减弱肺纤维化进展并恢复体重[7]。
Cell experiment [1]: | |
Cell lines | PC-3、LNCaP、PNT1A cells |
Preparation method | Cells were treated with SZL P1-41(5-20 μM ) for 3 days, and collected and labeled with Annexin-V-FITC and propidium iodide, followed by flow cytometry analysis. |
Reaction Conditions | 5-20 μM; 3 days |
Applications | SZL P1-41 displayed potent effects on cell viability of prostate cancer cell lines, including PC-3 and LNCaP cells, but only slightly affected cell viability of normal prostate epithelial PNT1A cells. |
Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation method | 769-P cells were mixed 1:1 with matrigel in a total volume of 0.2 ml, and then injected subcutaneously into right flank side of mice. When the tumor volume reached 100 mm3, which were randomized and treated with vehicle, MLN8237 (40 mg/kg/day, every day, p.o.), SZL P1-41 (80 mg/kg/day, every day, i.p.) and MLN8237+SZL P1-41. Nude mice were followed up for tumor size, and body weight. After 4 weeks of treatment, mice were euthanized. |
Dosage form | 80 mg/kg; i.p. |
Applications | A combination of MLN8237 and SZL P1-41 significantly inhibited tumor growth and induced apoptosis. |
References: | |
| Cas No. | 222716-34-9 | SDF | |
| 化学名 | 3-(benzo[d]thiazol-2-yl)-6-ethyl-7-hydroxy-8-(piperidin-1-ylmethyl)-4H-chromen-4-one | ||
| Canonical SMILES | CCC1=CC(C(C(C2=NC3=CC=CC=C3S2)=CO4)=O)=C4C(CN5CCCCC5)=C1O | ||
| 分子式 | C24H24N2O3S | 分子量 | 420.52 |
| 溶解度 | DMSO: 5 mg/mL (11.89 mM),DMF: 1 mg/ml,Ethanol: 0.3 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.378 mL | 11.89 mL | 23.7801 mL |
| 5 mM | 0.4756 mL | 2.378 mL | 4.756 mL |
| 10 mM | 0.2378 mL | 1.189 mL | 2.378 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.00%
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