TSI-01

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.