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| Product Name: | DO264 | | Synonyms: | N-[1-[3-Chloro-4-[2-chloro-4-(trifluoromethoxy)phenoxy]-2-pyridinyl]-4-piperidinyl]-N'-3-pyridinylthiourea;Thiourea, N-[1-[3-chloro-4-[2-chloro-4-(trifluoromethoxy)phenoxy]-2-pyridinyl]-4-piperidinyl]-N'-3-pyridinyl-;DO264;DO-264;DO 264;DO264
(DO-264;DO264 | | CAS: | 2301866-59-9 | | MF: | C23H20Cl2F3N5O2S | | MW: | 558.4 | | EINECS: | 604-604-1 | | Product Categories: | | | Mol File: | 2301866-59-9.mol |  |
| | DO264 Chemical Properties |
| Boiling point | 601.5±65.0 °C(Predicted) | | density | 1.52±0.1 g/cm3(Predicted) | | storage temp. | under inert gas (nitrogen or Argon) at 2–8 °C | | solubility | Soluble in DMSO (up to 30 mg/ml). | | form | solid | | pka | 11.53±0.70(Predicted) | | color | Pale yellow | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. |
| | DO264 Usage And Synthesis |
| Description | DO264 is an inhibitor of α/β-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-α, and IL-1β 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. | | Uses | DO264 is a potent inhibitor of ABHD12 (α/β-hydrolase domain-containing 12) which shows negligible interaction with other serine hydrolases as determined by activity-based protein profiling. | | References | 1) Ogasawara?et al.?(2019),?Discovery and Optimization of Selective and in Vivo Active Inhibitors of the Lysophosphatidylserine Lipase α/β-Hydrolase Domain-Containing 12 (ABHD12); J. Med. Chem.,?62?1643
2) Ogasawara?et al.?(2018),?Selective Blockade of the Lyso-PS Lipase ABHD12 Stimulates Immune Responses In Vivo; Nat. Chem. Biol.,?14?1099 |
| | DO264 Preparation Products And Raw materials |
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