DO264

DO264 is an inhibitor of alpha/beta-hydrolase domain-containing protein 12 (ABHD12, IC50 = 11 nM). It inhibits ABHD12-dependent hydrolysis of lysophosphatidylserine (lyso-PS) in mouse brain membrane lysates (IC50 = 2.8 nM) and human THP-1 cells. DO264 increases levels of chemokine (C-C motif) ligand 3 (CCL3), CCL4, TNF-alpha, and IL-1beta in M1-polarized THP-1 macrophages. It potentiates ferroptotic cell death induced by the glutathione peroxidase 4 (GPX4) inhibitor RSL3 in HT1080 fibrosarcoma and SU-DHL-5 B cell lymphoma cells when used at a concentration of 1 µM. In vivo, DO264 (30 mg/kg per day for four weeks) increases levels of 1-stearoyl-2-hydroxy-sn-glycero-3-PS, 1-arachidonoyl-2-hydroxy-sn-glycero-3-PS, 1-docosanoyl-2-hydroxy-sn-glycero-3-PS, 1-stearoyl-2-arachidonoyl-sn-glycero-3-PS, and 1-oleoyl-2-arachidonoyl-sn-glycero-3-PS in mouse brain. It increases levels of CCL2, CCL3, and CCL5 in bronchoalveolar lavage fluid (BALF) and decreases survival in a mouse model of infection with lymphocytic choriomeningitis virus (LCMV) clone 13 when administered at a dose of 30 mg/kg.Formal Name: N-[1-[3-chloro-4-[2-chloro-4-(trifluoromethoxy)phenoxy]-2-pyridinyl]-4-piperidinyl]-N'-3-pyridinyl-thiourea. CAS Number: 2301866-59-9. Molecular Formula: C23H20Cl2F3N5O2S. Formula Weight: 558.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. lambdamax: 259 nm. SMILES: S=C(NC1CCN(C2=C(Cl)C(OC3=CC=C(OC(F)(F)F)C=C3Cl)=CC=N2)CC1)NC4=CC=CN=C4. InChi Code: InChI=1S/C23H20Cl2F3N5O2S/c24-17-12-16(35-23(26,27)28)3-4-18(17)34-19-5-9-30-21(20(19)25)33-10-6-14(7-11-33)31-22(36)32-15-2-1-8-29-13-15/h1-5,8-9,12-14H,6-7,10-11H2,(H2,31,32,36). InChi Key: PIEQDBPBBQPLPL-UHFFFAOYSA-N.