达沙替尼盐酸盐作用机制 - Medchemexpress - MCE中国

1、Product Data SheetDasatinib hydrochlorideCat. No.: HY-10181ACAS No.: 854001-07-3分式: CHClNOS分量: 524.47作靶点: Bcr-Abl; Src; Autophagy; Apoptosis作通路: Protein Tyrosine Kinase/RTK; Autophagy; Apoptosis储存式: 4C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stored under nitrogen)溶解性数据体外实

2、验 DMSO : 15 mg/mL (28.60 mM; Need ultrasonic and warming)H2O : 10 mg/mL (19.07 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.9067 mL 9.5334 mL 19.0669 mL5 mM 0.3813 mL 1.9067 mL 3.8134 mL10 mM 0.1907 mL 0.9533 mL 1.9067 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

3、。储备液的保存式和期限：-80C, 6 months; -20C, 1 month (stored under nitrogen)。-80C 储存时，请在 6 个内使，-20C 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 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 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

4、 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 L 33.3 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.33

5、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 L 33.3 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合Page 1 of 2 www.MedChemE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 溶液，此案不适于实验周

6、期在半个以上的实验。以 1 mL 作液为例，取 100 L 33.3 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Dasatinib hydrochloride (BMS-354825 hydrochloride)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 & Target Ki: 16 pM (Src), 30 pM (Bcr-Abl)1

7、IC50: 1.0 (Bcr-Abl), 0.50 (Src), 0.40 (Lck), 0.50 (Yes), 5.0 (c-Kit), 28 (PDGFR), 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, PDGFR, p38, Her1, Her2, FGFR-1, andMEK with IC50s of 1.0, 0.50, 0.40, 0

8、.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively1.Dasatinib shows antiproliferative activities aversus K562 chronic myelogenous leukemia (CML), PC3 human prostatetumor, MDA-MB-231 human breast tumor, and WiDr human colon tumor cell lines with IC50s of 1.0 nM, 9.4 nM, 12nM, and 52 nM, resp

9、ectively1.体内研究 Dasatinib (5 mg/kg and 50 mg/kg, qd10d, 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 levels1.Dasatinib (10 mg/kg) has

10、 a pharmacokinetic profile appropriate for continued advancement into in vivo efficacystudies. 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: Nude mice bearing K562 xen

11、ograftsDosage: 5 mg/kg and 50 mg/kgAdministration: Oral administration on a 5 day on and 2 day off schedule.Result: Showed partial tumor regressions after one treatment cycle and completedisappearance of the tumor mass by the end of drug treatment. No toxicity (animal deaths, lack of weight gain) wa

12、s observed.Animal Model: Sprague-Dawley RatsDosage: 10 mg/kg (Pharmacokinetic Analysis)Administration: Oral and i.v.Result: Cmax of 13.2 and 0.5 M for i.v. and oral, respectively.户使本产品发表的科研献Page 2 of 3 www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Nat Biomed Eng. 2018;2:578-588. J

13、 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 HYPERLINK www.MedChemE www.MedChemEREFERENCES1. 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.McePdfHeightCauti