TSI-01
目录号 : GC41638TSI-01是溶血磷脂酰胆碱酰基转移酶2（LPCAT2）的选择性抑制剂，对人 LPCAT2和LPCAT1的IC50值分别为0.47和3.02µM。
Cas No.:704878-75-1
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
Cell lines | HT29 cells |
Preparation Method | HT29 cells treated with vehicle (DMSO) or selective LPCAT2 inhibitor TSI-01 (10µM) for 48 h. |
Reaction Conditions | 10μM; 48h |
Applications | TSI-01 in HT29 cells significantly prevented lipid droplet (LD) accumulation especially induced by 5-fluorouracil (5-Fu) and oxaliplatin (Oxa) alone or in combination (FOX) treatments. |
References: | |
TSI-01 is a selective inhibitor of lysophosphatidylcholine acyltransferase 2 (LPCAT2) with IC50 values of 0.47 and 3.02 µM for human LPCAT2 and LPCAT1, respectively. LPLAT selectively incorporates fatty chains into lysophospholipids to affect the fatty acid composition of membrane glycerophospholipids [1, 2]. TSI-01 can inhibit the production of platelet-activating factor (PAF) in macrophages, which is rapidly biosynthesized by lyso-PAF acetyltransferase (lyso-PAFAT) [3].
In vitro, treatment of HT29 cells with TSI-01 (10 μM) for 48 h significantly prevented lipid droplet accumulation caused by 5-fluorouracil (5-Fu) and oxaliplatin (Oxa) alone or in combination [4]. TSI-01 (0-30 μM) treated endometrial cancer cell lines, inhibited cell proliferation in a dose-dependent manner, with IC50 values of 7.56 μM and 9.31 μM in Ishikawa cell lines and HEC-1A cell lines, respectively, and promoted cell apoptosis[5].
References:
[1] Tarui M, Shindou H, Kumagai K, et al. Selective inhibitors of a PAF biosynthetic enzyme lysophosphatidylcholine acyltransferase 2 [S][J]. Journal of lipid research, 2014, 55(7): 1386-1396.
[2] Valentine W J, Hashidate–Yoshida T, Yamamoto S, et al. Biosynthetic enzymes of membrane glycerophospholipid diversity as therapeutic targets for drug development[J]. Druggable Lipid Signaling Pathways, 2020: 5-27.
[3] Shindou H, Shiraishi S, Tokuoka S M, et al. Relief from neuropathic pain by blocking of the platelet-activating factor–pain loop[J]. The FASEB Journal, 2017, 31(7): 2973.
[4] Cotte A K, Aires V, Fredon M, et al. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance[J]. Nature communications, 2018, 9(1): 322.
[5] Zhao T, Sun R, Ma X, et al. Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating TGF-β/Smad2/3 signaling pathway: Tumor-promoting effect of LPCAT1 in endometrial cancer[J]. Acta Biochimica Et Biophysica Sinica, 2022, 54(7): 904.
TSI-01是溶血磷脂酰胆碱酰基转移酶2（LPCAT2）的选择性抑制剂，对人 LPCAT2和LPCAT1的IC50值分别为0.47和3.02µM。LPLAT选择性地将脂肪链掺入溶血磷脂中，以影响膜甘油磷脂的脂肪酸组成[1, 2]。TSI-01可以抑制巨噬细胞中血小板激活因子（PAF）的产生，PAF由溶血PAF乙酰转移酶 （lyso-PAFAT）快速生物合成[3]。
在体外，TSI-01（10μM）处理HT29细胞48h，显著防止了由5-氟尿嘧啶（5-Fu）和奥沙利铂（Oxa）单独或联合治疗引起的脂滴积聚[4]。TSI-01（0-30μM）处理子宫内膜癌细胞系，剂量依赖性地抑制了细胞增殖，在Ishikawa细胞系和HEC-1A细胞系中的IC50分别为7.56μM、9.31μM，并促进细胞凋亡[5]。
| Cas No. | 704878-75-1 | SDF | |
| Canonical SMILES | O=C(C(Cl)=C1Cl)N(C2=CC=C(C(OC(C)C)=O)C=C2)C1=O | ||
| 分子式 | C14H11Cl2NO4 | 分子量 | 328.2 |
| 溶解度 | DMF: 50 mg/ml,DMF:PBS (pH 7.2)(1:3): 0.25 mg/ml,DMSO: 30 mg/ml,Ethanol: 1 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0469 mL | 15.2346 mL | 30.4692 mL |
| 5 mM | 0.6094 mL | 3.0469 mL | 6.0938 mL |
| 10 mM | 0.3047 mL | 1.5235 mL | 3.0469 mL |
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| 给药剂量 | mg/kg |  |
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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Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/β-Smad2/3 signaling pathway
Acta Biochim Biophys Sin (Shanghai) 2022 Jun 25;54(7):904-916.PMID:35880567DOI:10.3724/abbs.2022076.
The incidence of endometrial cancer (EC) increases annually and tends to occur in younger women. A particularly important relationship exists between EC and metabolic disorders. As one of the most important components of lipid metabolism, phospholipids play an indispensable role in metabolic balance. LPCAT1 is a key enzyme regulating phospholipid metabolism. In this study, we perform further investigations to seek mechanistic insight of LPCAT1 in EC. Our results demonstrate that silencing of LPCAT1 inhibits the growth of endometrial cancer, while overexpression of LPCAT1 results in enhanced stemness and metastasis in endometrial cancer cell lines. Meanwhile, the contents of various phospholipids including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and triglyceride (TG) change significantly after overexpression of LPCAT1. In addition, through RNA-sequencing and western blot analysis, we observe that the TGF-β/Smad2/3 signaling pathway is of great importance in the tumor-promoting function of LPCAT1. LPCAT1 promotes the expressions of stem cell-related transcription factors and epithelial-mesenchymal transition (EMT) related proteins through the TGF-β/Smad2/3 signaling pathway. Moreover, we find that TSI-01, which can inhibit the activity of LPCAT1, is able to restrain the proliferation of EC cell lines and promote cell apoptosis. Collectively, we demonstrate that LPCAT1 enhances the stemness and metastasis of EC by activating the TGF-β/Smad2/3 signaling pathway and that TSI-01 may have potential use for the treatment of EC.