| Identification | Back Directory | [Name]
DO264 | [CAS]
2301866-59-9 | [Synonyms]
DO264
DO264
(DO-264
DO264;DO-264;DO 264
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- | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C23H20Cl2F3N5O2S | [MDL Number]
MFCD31812603 | [MOL File]
2301866-59-9.mol | [Molecular Weight]
558.4 |
| Chemical Properties | Back Directory | [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. |
| Hazard Information | Back Directory | [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. | [in vivo]
Mice treated with DO-264 display dose-dependent increases in brain lyso-PS and 20:4 PS content that are qualitatively similar to the changes observed in ABHD12–/– mice. DO-264-treated mice, however, show minimal impairment in auditory function following four weeks of drug exposure. Both ABHD12–/– and DO-264-treated mice display exacerbated immunopathology following infection with the lymphocytic choriomeningitis virus (LCMV) clone 13, resulting in severe inflammatory lung damage, heightened chemokine production, and, in some cases, death[1]. | [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 |
|
| Company Name: |
Syntechem Co.,Ltd.
|
| Tel: |
519-88298820 15861130028 |
| Website: |
http://www.syntechem.com |
| Company Name: |
DC Chemicals
|
| Tel: |
021-58447131 13564518121 |
| Website: |
m.approvedhomemanagement.com/showsupplierproductslist927327/0.htm |
|