DWK-1339|cas 1018946-38-7|DC Chemicals

Cas No.:	1018946-38-7
Chemical Name:	2H-Benzimidazol-2-one, 1-[(2R)-2,3-dihydroxypropyl]-1,3-dihydro-3-[1-[(1R,3S,4S)-spiro[bicyclo[2.2.1]
Synonyms:	2H-Benzimidazol-2-one, 1-[(2R)-2,3-dihydroxypropyl]-1,3-dihydro-3-[1-[(1R,3S,4S)-spiro[bicyclo[2.2.1];2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl)-1-benzofuran;2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl)benzofuran;2-(3,4-dimethoxy-phenyl)-5-(3-methoxy-propyl)-benzofuran;Benzofuran, 2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl)-;DWK-1339;SureCN3002082;UNII-WN8TEM4Q1F;MDR-1339
SMILES:	COCCCC1=CC=C(OC(C2=CC=C(OC)C(OC)=C2)=C3)C3=C1
Formula:	C₂₀H₂₂O₄
M.Wt:	326.38628
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	DWK-1339 is an orally active and blood-brain-barrier-permeable Aβ-aggregation inhibitor, used in the research of Alzheimer's disease.
In Vivo:	DWK-1339 (0.1-10 mg/kg, p.o.) dose-dependently restores the passive avoidance responses in mice models of Alzheimer's disease (AD), with an ED50 of 0.19 mg/kg. DWK-1339 (30 and 100 mg/kg, p.o. daily for 8 weeks) significantly improves spontaneous alternation, and reduces the Aβ1-40 and Aβ1-42 levels in APP/PS1 mice[1].
In Vitro:	DWK-1339 (MDR-1339) is an Aβ-aggregation inhibitor, and shows no significant inhibition a panel of CYP isozymes, while it slightly inhibits CYP2C8 (IC50, 31.4 μM). DWK-1339 (3.1-50 μM) dose-dependently blocks the formation of Aβ aggregates, and disaggregates Aβ fibrils. DWK-1339 (1.5-10 μM) also protects cells from this Aβ-induced toxicity[1].
Cell Assay:	HT22 cells, a murine cell line of hippocampal origin, are grown in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum and 5% penicillin/streptomycin. At the outset, 90% confluent cells are dissociated and plated at 5 × 103 cells/well in a 96-well plate. When the cells are attached to the plate, the medium is replaced with plain DMEM. The cells are treated with DWK-1339. One hour after DWK-1339 treatment, 4 μL of pre-diluted 25 μM Aβ42 is added to the media, and the cells are further incubated for 18 h. For the determination of cell viability, 15 μL of 5 mg/mL MTT is added to each well and incubated for 3 h. The formazan that formed is dissolved in DMSO, and the absorbance is measured at 570-630 nm using a plate reader[1].
Animal Administration:	For this study, a total of 24 (n = 8 for each group) APP/PS1 [B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/J] Tg mice are utilized. The mice are housed in a controlled environment under standard room temperature, relative humidity and a 12 h light/dark cycle with free access to food and water. APP/PS1 treated groups are orally administered with DWK-1339 at a dose of 30 or 100 mg/kg body weight once daily. DWK-1339 treatment is at the age of 29 weeks, and the treatment is conducted for 8 weeks[1].
References:	[1]. Ha HJ, et al. Discovery of an Orally Bioavailable Benzofuran Analogue That Serves as a β-Amyloid Aggregation Inhibitor for the Potential Treatment of Alzheimer's Disease. J Med Chem. 2018 Jan 11;61(1):396-402.

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