LYPLAL1-IN-1 

LYPLAL1-IN-1 (compound 11) is a selective, covalent, and irreversible inhibitor of the lysophospholipase-like enzyme LYPLAL1 (IC₅₀ = 6 nM). LYPLAL1-IN-1 shows selectivity against other serine hydrolases such as carboxylesterase CES1 (IC₅₀ > 50 μM for CES1). LYPLAL1-IN-1 inhibits the depalmitoylation function of LYPLAL1, blocking its depalmitoylation modification of cyclic GMP-AMP synthase (cGAS), thereby promoting cGAS dimerization and activation, and initiating the cGAS-STING pathway-mediated innate immune response. LYPLAL1-IN-1 can enhance DNA-induced type I interferon production, upregulate PD-L1 expression in tumor cells, and promote the accumulation of tumor-infiltrating CD8⁺ T cells, with the core function of strengthening the anti-tumor immune response. LYPLAL1-IN-1 is primarily used in tumor immunology research, especially in combination with PD-1/PD-L1 inhibitors^[1][2].

IC50: 0.006 μM (LYPLAL1-IN-1)^[1]

LYPLAL1-IN-1 (30 min) showed potent inhibitory activity against human recombinant LYPLAL1 in in vitro enzyme inhibition assays, with an IC₅₀ of 0.006 μM, and no significant inhibitory effect on CES1 (IC₅₀ > 50 μM)^[1].
LYPLAL1-IN-1 (compound 11) (10 μM, 20 μM; 24 h) increased cGAS palmitoylation levels in MDA-MB-231 cells, promoted HT-DNA-induced IRF3 phosphorylation, and at a concentration of 20 μM, enhanced cGAS dimerization and upregulated PD-L1 protein expression^[2].
LYPLAL1-IN-1 (20 μM; 24 h) significantly increased the mRNA expression levels of IFNβ1 and CXCL10 in MDA-MB-231 cells, and this effect was dependent on cGAS^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

539.59

C₂₉H₂₉N₇O₄

1966129-74-7

Solid

White to off-white

O=C([C@H]1[C@H](C2=CC=CC=C2)N(C(N3N=C(C4=CC=C(C5=CN=C(N6CCOCC6)N=C5)C=C4)N=C3)=O)CCC1)O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

* 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 (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Ahn K, et al. Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism. ACS Chem Biol. 2016 Sep 16;11(9):2529-40.  [Content Brief]

  [2]. Fan Y, et al. Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy. Mol Cell. 2023 Oct 5;83(19):3520-3532.e7.  [Content Brief]