达沙替尼盐酸盐作用机制- Medchemexpress- MCE中国

Product Data?SheetDasatinib hydrochlorideCat. No.:CAS No.:分?式:分?量:作?靶点:作?通路:储存?式:HY-10181A854001-07-3C??H??Cl?N?O?S524.47Bcr-Abl; Src; Autophagy; ApoptosisProtein Tyrosine Kinase/RTK; Autophagy; Apoptosis4°C, stored under nitrogen* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)Inhibitors?Agonists?Screening Libraries溶解性数据体外实验DMSO : 15 mg/mL (28.60 mM; Need ultrasonic and warming)H2O : 10 mg/mL (19.07 mM; Need ultrasonic)Mass1 mg5 mg10 mgSolventConcentration制备储备液1 mM5 mM10 mM1.9067 mL0.3813 mL0.1907 mL9.5334 mL1.9067 mL0.9533 mL19.0669 mL3.8134 mL1.9067 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；?旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存?式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个?内使?，-20°C 储存时，请在 1 个?内使?。体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照 In Vitro ?式配制澄清的储备液，再依次添加助溶剂： 为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的?作液，建议您现?现配，当天使?； 以下溶剂前显?的百分?是指该溶剂在您配制终溶液中的体积占?；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的?式助溶1. 请依序添加每种溶剂：?10% DMSO ?? 40% PEG300 ?? 5% Tween-80 ?? 45% salineSolubility: ≥ 3.33 mg/mL (6.35 mM); Clear solution此?案可获得 ≥ 3.33 mg/mL (6.35 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 33.3 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加? 50 μL Tween-80，混合均匀；然后继续加? 450 μL ?理盐?定容? 1 mL。2. 请依序添加每种溶剂：?10% DMSO ?? 90% (20% SBE-β-CD in saline)Solubility: ≥ 3.33 mg/mL (6.35 mM); Clear solution此?案可获得 ≥ 3.33 mg/mL (6.35 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 33.3 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD ?理盐??溶液中，混合Page 1 of 2 www.MedChemExpress.cn

均匀。3. 请依序添加每种溶剂：?10% DMSO ?? 90% corn oilSolubility: ≥ 3.33 mg/mL (6.35 mM); Clear solution此?案可获得 ≥ 3.33 mg/mL (6.35 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。 以 1 mL ?作液为例，取 100 μL 33.3 mg/mL 的澄清 DMSO 储备液加到 900 μL ??油中，混合均匀。BIOLOGICAL ACTIVITY?物活性Dasatinib hydrochloride (BMS-354825 hydrochloride) 是?种具有?服活性的，ATP 竞争性的 Src/Bcr-Abl 双重抑制剂，对 Src 和 Bcr-Abl 作?的 Ki 值分别为 16 pM 和 30 pM。Dasatinib hydrochloride 具有有效的抗肿瘤活性[1]。IC?? & TargetKi: 16 pM (Src), 30 pM (Bcr-Abl)[1] IC50: <1.0 (Bcr-Abl), 0.50 (Src), 0.40 (Lck), 0.50 (Yes), 5.0 (c-Kit), 28 (PDGFRβ), 100 (p38), 180 (Her1), 720 (Her2), 880 (FGFR-1), 1700 (MEK)[1]体外研究Dasatinib demonstrates significant activity against Bcr-Abl, Src, Lck, Yes, c-Kit, PDGFRβ, p38, Her1, Her2, FGFR-1, and MEK with IC50s of <1.0, 0.50, 0.40, 0.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively[1]. Dasatinib shows antiproliferative activities aversus K562 chronic myelogenous leukemia (CML), PC3 human prostate tumor, MDA-MB-231 human breast tumor, and WiDr human colon tumor cell lines with IC50s of <1.0 nM, 9.4 nM, 12 nM, and 52 nM, respectively[1].体内研究Dasatinib (5 mg/kg and 50 mg/kg, qd×10d, 5 on-2 off) possesses potent antitumor activity and a high safety margin in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels[1]. Dasatinib (10 mg/kg) has a pharmacokinetic profile appropriate for continued advancement into in vivo efficacy studies. Dasatinib (10 mg/kg) demonstrates favorable half-lives (t1/2s) of 3.3 and 3.1 h for i.v. and oral, respectively. The oral bioavailability (Fpo) in this study is 27%[1].Animal Model:Dosage:Administration:Result:Nude mice bearing K562 xenografts 5 mg/kg and 50 mg/kgOral administration on a 5 day on and 2 day off schedule.Showed partial tumor regressions after one treatment cycle and complete disappearance of the tumor mass by the end of drug treatment. No toxicity (animal deaths, lack of weight gain) was observed.Animal Model:Dosage:Administration:Result:Sprague-Dawley Rats 10 mg/kg (Pharmacokinetic Analysis)Oral and i.v.Cmax of 13.2 and 0.5 μM for i.v. and oral, respectively.客户使?本产品发表的科研?献Page 2 of 3 www.MedChemExpress.cn

????Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.????Nat Biomed Eng.?2018;2:578-588.?????J Pineal Res. 2019 Sep;67(2):e12588.????J Clin Invest. 2019 Mar 1;129(3):972-987.????Nat Commun. 2020 Apr 14;11(1):1790.

See more customer validations on www.MedChemExpress.cnREFERENCES

[1].?Lombardo LJ, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004 Dec 30;47(27):6658-61.

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