| Fostamatinib (R788)Spleen tyrosine kinase (Syk) inhibitor |
Sample solution is provided at 25 µL, 10mM.
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Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.15%
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| Cell experiment [1]: | |
Cell lines | Diffuse large B-cell lymphoma (DLBCL) cell lines |
Preparation method | The solubility of this compound in DMSO is > 100.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | 4 μM, 96 h |
Applications | R788 was a prodrug of the active metabolite. R406 induced apoptosis of the majority of examined DLBCL cell lines. In R406-sensitive DLBCL cell lines, R406 specifically inhibited both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). |
| Animal experiment [2]: | |
Animal models | Eμ- TCL1 transgenic mouse model of CLL, B6/C3H F1 mice |
Dosage form | Intraperitoneal administration, 18 consecutive days at a daily dose of 80 mg/kg |
Application | R788 (80 mg/kg/d) inhibited the growth of adoptively transferred TCL1 leukemias in vivo. R788 treatment administered from days 4 to 25 after adoptive transfer significantly prevented the outgrowth of leukemias. Treatment with R788 significantly prolonged the survival of the animals. In B6/C3H mice, after 4 days of treatment animals receiving R788 showed a greater rise in the number of circulating malignant lymphocytes than controls. In B6/C3H F1 mice, treatment with R788 for 7 days blocked BCR signaling and inhibited leukemic cell survival and proliferation in vivo. In Eμ- TCL1 transgenic mouse model of CLL, R788 inhibited the growth of spontaneously developing TCL1 leukemias. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Chen L, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma[J]. Blood, 2008, 111(4): 2230-2237. [2]. Suljagic M, Longo P G, Bennardo S, et al. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Eμ-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling[J]. Blood, 2010, 116(23): 4894-4905. | |
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| Cas No. | 901119-35-5 | SDF | Download SDF |
| Chemical Name | [6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate | ||
| Canonical SMILES | CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C | ||
| Formula | C23H26FN6O9P | M.Wt | 580.46 |
| Solubility | ≥100.4mg/mL in DMSO | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Fostamatinib is a small molecule inhibitor of spleen tyrosine kinase (Syk) with IC50 value of 41nM [1].
Fostamatinib is an orally bioavailable prodrug of R406. It is developed for the treatment of autoimmune diseases. The effective metabolite of fostamatinib, R406, is an ATP-competitive inhibitor of Syk with Ki value of 30nM. R406 also inhibits the activity of other kinases including Flt3, Lyn (IC50=63nM) and Lck (IC50=37nM). It is found that R406 inhibits both BCR and FcR mediated responses in vitro. Besides that, R406 also shows effects in other cells types and signalling pathways. In the in vivo assay, fostamatinib shows to be highly active to inhibit FcR-mediated signaling in various animal models of allergy, autoimmunity and inflammation. Moreover, fostamatinib also exerts efficacy in SLE animal models. Treatment of fostamatinib suppresses the established renal and skin disease and reduces lymphadenopathy in the MRL/lpr strain [1].
References:[1] McAdoo S P, Tam F W K. Fostamatinib disodium. Drugs of the future, 2011, 36(4): 273.
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培养一段时间后（一般小于一个细胞周期），固定细胞。根据所使用模拟核苷酸的不同，使用不同的方法。EdU，改变缓冲液的pH值，就会发出荧光。而BrdU则需用荧光抗体识别，需要对细胞膜和核膜进行通透处理。
再加入PI对DNA染色。
在二维坐标图上，横坐标设为线性PI荧光强度，纵坐标设为模拟核苷酸的荧光强度（log）。
典型的图就像下面一样：
G1, G2 和S期就按照图中的划分来做。G1期的细胞没有新合成DNA，所以BrdU信号是阴性，而PI的信号位于1倍体期。S期是正在合成DNA，所以BrdU都是阳性。G2期是已经合成好了2倍的DNA，所以位于2倍体期，信号是G1期的一倍。这个图中，G1 PI信号是300， G2就是600.
流式细胞仪（Flow cytometry ）是对细胞进行自动分析和分选的装置。它可以快速测量、存贮、显示悬浮在液体中的分散细胞的一系列重要的生物物理、生物化学方面的特征参量，并可以根据预选的参量范围把指定的细胞亚群从中分选出来。多数流式细胞计是一种零分辨率的仪器，它只能测量一个细胞的诸如总核酸量，总蛋白量等指标，而不能鉴别和测出某一特定部位的核酸或蛋白的多少。也就是说，它的细节 分辨率为零。
染色的各种染料，标记好的荧光抗体染色所需要的缓冲液，封闭液，PBS最终由于上样的缓冲液
不过还要考虑很多因素：标记的方法会不会影响细胞下面的培养细胞是否能够耐受长时间接触房间中的氧气和二氧化碳的浓度机器的无菌情况
（溶血）：红细胞，血红蛋白分解，红细胞溶解逃逸所述，称为溶血。通过各种物理和化学因素和毒素。在体外，如低渗溶液中，强烈的机械振荡，突然冷冻（-20℃-25℃）或突然化冻，过酸或过碱，以及乙醇，乙醚，皂碱，胆碱盐可引起溶血。人血浆的等渗溶液为0.9％NaCl溶液，红细胞在低于0.45％的NaCl溶液中，由于水的渗透，肿胀和红细胞破裂，血红蛋白逸出。在体内，溶血溶血性细菌侵入或某些毒素的抗原 - 抗体反应（如输入配血不合的血液），各种机械性损伤，红细胞内在（膜，酶）引起某些药物的缺陷。溶血性细菌，如某些溶血性链球菌和产气荚膜梭菌可导致败血症。的红血细胞和某些溶血性毒液含酶卵磷脂，卵磷脂血浆或红细胞成溶血卵磷脂，使红细胞膜分解疟原虫破坏。
比较常用的是用计数微球。比如临床上的CD4细胞绝对计数，就是采用这个方法。试管内事先已经有固定数目的计数微球和染色抗体。按要求加入固定体积的抗凝血液，裂解红细胞后上机。记录一千个微球，同时就会得到不同染色区域细胞的数量。这样就可以算出单位体积血液内CD4细胞的绝对数目了。
这样的计数微球也可以另外购买。浓度是固定的。在你已知体积的细胞悬液中加入一定体积的微球后上机，记录一千个微球的数据，细胞的计数也会同时记录。根据微球的浓度就可以推算出细胞的浓度，从而得出绝对计数了
另外一个方法是有些流式细胞仪是使用微泵加样，而不是连续吸取样本，这样样本的体积是已知的，记录一次就是所有样本的数量，可以算出细胞浓度
