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).

pka

11.53±0.70(Predicted)

form 

solid

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

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