ZSET1446-ST-101-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEZSET1446Cat. No.: HY-11013CAS No.: 887603-94-3Synonyms: ST-101分式: CHNO分量: 236.27作靶點(diǎn): Calcium Channel; nAChR作通路: Membrane Transporter/Ion Channel; Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 34 mg/mL (143.90 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 4.2324 mL 21.1622 mL 42.3245 mL5 mM 0.8465 mL 4.2324 mL 8.4649 mL10 mM 0.4232 mL 2.1162 mL 4.2324 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性

3、 ZSET1446種新穎的促進(jìn)認(rèn)知藥，在不同的阿爾茨海默病模型中，能夠改善學(xué)習(xí)功能障礙。體外研究ZSET1446 (100 pM-10 nM) exerts limited effects on the basal neuronal excitability and synaptictransmission. ZSET1446 potentiates the facilitatory effect of nAChR stimulation on sPSC frequency.ZSET1446 potentiates the increase in sIPSC frequency by loca

4、l application of nicotine (5 M; 2 minutes)1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEwithout affecting the basal sIPSC frequency at the range of 10 pM to 1 nM 1.體內(nèi)研究 ZSET1446 enhances object recognition memory in mice and ameliorates cognitive impairment caused byscopolamine in rats. Concomita

5、nt administration of subeffective doses of ZSET1446 and memantinesignificantly ameliorates the cognitive performance in the novel object recognition task in both mice and rats.Moreover, oral administration of ZSET1446 or memantine increases the extracellular level of ACh in thehippocampus as compare

6、d with the control. Further, concomitant administration of subeffective doses ofZSET1446 and memantine significantly increases the extracellular level of ACh as compared with the groupof ZSET1446 or memantine alone 2. ZSET1446 (0.002, 0.01, and 0.1 mg/kg, p.o.) ameliorates cognitivedeficits of SAMP8

7、 after 4, 8, 12, and 16 weeks of treatment in a novel object recognition test. ZSET1446 alsoreduces grading scores of SAMP8 after 16 weeks of treatment. Further, 8-week treatment of ZSET1446significantly reduces the total number of A-positive granules in the hippocampus 3.PROTOCOLAnimal The experime

8、ntal apparatus consists of a Plexiglas open-field box 25 cm (width) 41 cm (length) 17 cmAdministration 2 (depth), model TP-105, the floor of which is covered with sawdust. The apparatus is located in a sound-attenuated room. The procedure for the novel object recognition task consists of three diffe

9、rent sessions:habituation, training, and retention sessions. Each mouse is individually habituated to the box, with 10 min ofexploration in the absence of objects (day 1: habituation session). ZSET1446 at doses of 0.001, 0.003, 0.01,and 0.03 mg/kg and/or memantine at doses of 3 and 10 mg/kg is orall

10、y administered 60 min before thetraining trial. In the experiment of injection of nicotinic receptor antagonists, oral administration of ZSET1446and i.p. injection of mechamylamine or DHbE at each dose of 1 mg/kg are given 60 min before the trainingtrial. During the training session, two different n

11、ovel objects are symmetrically fixed to the floor in the box,and each animal is allowed to explore in the box for 10 min (day 2: training session). These objects aredifferent in shape and color but similar in size. The mice are considered to be exploring the object when themouse is facing, touching,

12、 or sniffing the object. The time spent for exploring each object ismanuallymeasured by a stopwatch. In the training session, locomotor activity is simultaneously measured fora period of 10 min automatically, using an Animex Auto placed under the open-field box. After the trainingtrial, mice are imm

13、ediately returned to their home cages.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Takeda K, et al. Potentiation of Acetylcholine-Mediated Facilitation of Inhibitory Synaptic Transmission by an Azaindolizione Derivative,ZSET1446 (ST101),

14、 in the Rat Hippocampus. J Pharmacol Exp Ther. 2016 Feb;356(2):445-55.2. Yamaguchi Y, et al. Combination effects of ZSET1446/ST101 with memantine on cognitive function and extracellular acetylcholine in thehippocampus. J Pharmacol Sci. 2013;123(4):347-55. Epub 2013 Nov 29.3. Yamaguchi Y, et al. Effects of ZSET1446/ST101 on cognitive deficits and amyloid deposition in the senescence accelerated pronemouse brain. J Pharmacol Sci. 20