Tofacitinib-d3 (citrate)
(Synonyms: Tasocitinib-d3 citrate; CP-690550-d3 citrate) 目录号 : GC49692
An internal standard for the quantification of tofacitinib
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tofacitinib-d3 (citrate) is intended for use as an internal standard for the quantification of tofacitinib by GC- or LC-MS. Tofacitinib is a potent, cell-permeable inhibitor of all JAK isoforms (IC50s = 6.1, 12, and 8 nM for JAK1, JAK2, and JAK3, respectively).1 It is selective for JAK1-3 over ROCK-2 and Lck (IC50s = 3,400 and 3,870 nM, respectively) as well as 28 additional kinases in enzyme assays (IC50s = >10,000 nM). It inhibits IL-2-mediated phosphorylation of JAK3 and STAT5 when used at a concentration of 30 ng/ml.2 Tofacitinib prevents rejection and prolongs survival in murine and cynomolgus monkey models of heterotopic heart and kidney transplantation, respectively. Formulations containing tofacitinib have been used in the prevention of organ allograft rejection as well as in the treatment of the inflammatory or autoimmune components of a host of diseases, including rheumatoid arthritis and ulcerative colitis.2,3,4,5
1.Haan, C., Rolvering, C., Raulf, F., et al.Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptorsChem. Biol.18(3)314-323(2011) 2.Changelian, P.S., Flanagan, M.E., Ball, D.J., et al.Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitorScience302(5646)875-878(2003) 3.Flanagan, M.E., Blumenkopf, T.A., Brissette, W.H., et al.Discovery of CP-690,550: A potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejectionJ. Med. Chem.53(24)8468-8484(2010) 4.Cutolo, M.The kinase inhibitor tofacitinib in patients with rheumatoid arthritis: Latest findings and clinical potentialTher. Adv. Musculoskelet. Dis.5(1)3-11(2013) 5.Sandborn, W.J., Ghosh, S., Panes, J., et al.Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitisN. Engl. J. Med.367(7)616-624(2012)
| Cas No. | N/A | SDF | Download SDF |
| 别名 | Tasocitinib-d3 citrate; CP-690550-d3 citrate | ||
| Canonical SMILES | O=C(CC#N)N1CC[C@@H](C)[C@@H](N(C([2H])([2H])[2H])C2=NC=NC3=C2C=CN3)C1.OC(CC(O)=O)(C(O)=O)CC(O)=O | ||
| 分子式 | C16H17D3N6O • C6H8O7 | 分子量 | 507.5 |
| 溶解度 | DMSO: soluble,Water: soluble | 储存条件 | -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9704 mL | 9.8522 mL | 19.7044 mL |
| 5 mM | 0.3941 mL | 1.9704 mL | 3.9409 mL |
| 10 mM | 0.197 mL | 0.9852 mL | 1.9704 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Effects of sodium citrate, citric acid and lactic acid on human blood coagulation
Perfusion 2018 Oct;33(7):577-583.PMID:29783879DOI:10.1177/0267659118777441.
Introduction: Citric acid infusion in extracorporeal blood may allow concurrent regional anticoagulation and enhancement of extracorporeal CO2 removal. Effects of citric acid on human blood thromboelastography and aggregometry have never been tested before. Methods: In this in vitro study, citric acid, sodium citrate and lactic acid were added to venous blood from seven healthy donors, obtaining concentrations of 9 mEq/L, 12 mEq/L and 15 mEq/L. We measured gas analyses, ionized calcium (iCa++) concentration, activated clotting time (ACT), thromboelastography and multiplate aggregometry. Repeated measure analysis of variance was used to compare the acidifying and anticoagulant properties of the three compounds. Results: Sodium citrate did not affect the blood gas analysis. Increasing doses of citric and lactic acid progressively reduced pH and HCO3- and increased pCO2 (p<0.001). Sodium citrate and citric acid similarly reduced iCa++, from 0.39 (0.36-0.39) and 0.35 (0.33-0.36) mmol/L, respectively, at 9 mEq/L to 0.20 (0.20-0.21) and 0.21 (0.20-0.23) mmol/L at 15 mEq/L (p<0.001). Lactic acid did not affect iCa++ (p=0.07). Sodium citrate and citric acid similarly incremented the ACT, from 234 (208-296) and 202 (178-238) sec, respectively, at 9 mEq/L, to >600 sec at 15 mEq/L (p<0.001). Lactic acid did not affect the ACT values (p=0.486). Sodium citrate and citric acid similarly incremented R-time and reduced α-angle and maximum amplitude (MA) (p<0.001), leading to flat-line thromboelastograms at 15 mEq/L. Platelet aggregometry was not altered by any of the three compounds. Conclusions: Citric acid infusions determine acidification and anticoagulation of blood similar to lactic acid and sodium citrate, respectively.
Extracellular citrate and metabolic adaptations of cancer cells
Cancer Metastasis Rev 2021 Dec;40(4):1073-1091.PMID:34932167DOI:10.1007/s10555-021-10007-1.
It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.
citrate chemistry and biology for biomaterials design
Biomaterials 2018 Sep;178:383-400.PMID:29759730DOI:10.1016/j.biomaterials.2018.05.003.
Leveraging the multifunctional nature of citrate in chemistry and inspired by its important role in biological tissues, a class of highly versatile and functional citrate-based materials (CBBs) has been developed via facile and cost-effective polycondensation. CBBs exhibiting tunable mechanical properties and degradation rates, together with excellent biocompatibility and processability, have been successfully applied in vitro and in vivo for applications ranging from soft to hard tissue regeneration, as well as for nanomedicine designs. We summarize in the review, chemistry considerations for CBBs design to tune polymer properties and to introduce functionality with a focus on the most recent advances, biological functions of citrate in native tissues with the new notion of degradation products as cell modulator highlighted, and the applications of CBBs in wound healing, nanomedicine, orthopedic, cardiovascular, nerve and bladder tissue engineering. Given the expansive evidence for citrate's potential in biology and biomaterial science outlined in this review, it is expected that citrate based materials will continue to play an important role in regenerative engineering.
Pharmaceutical versus Over-the-Counter Potassium citrate: A Benchtop Comparison
Urol Pract 2022 May;9(3):205-211.PMID:37145541DOI:10.1097/UPJ.0000000000000300.
Introduction: Potassium citrate has been shown to significantly reduce kidney stone recurrence by alkalinizing urine and increasing citrate excretion. However, the cost of potassium citrate can be prohibitive. Thus, over-the-counter use of potassium citrate supplements has gained interest from patients and providers due to reported decreased cost. Prior studies show that fluids such as orange juice, Crystal Light and certain sodas are reasonable sources of alkali citrate; however, the true alkali citrate content among leading over-the-counter supplements is unknown. We investigate popular supplements and compare them to pharmaceutical potassium citrate. Methods: The top 6 potassium citrate supplements were purchased from Amazon.com in October 2020 and April 2021. These supplements and Urocit®-K were dissolved in deionized water and diluted before measurement with a colorimetric citrate assay kit. A pH electrode was used to measure the pH of each sample and the alkali citrate content of each supplement was calculated. Results: Urocit-K and Thorne® had the highest percentage of alkali citrate per gram. NOW® supplements and Nutricost® offered the cheapest alkali citrate at less than 1 cent per mEq. Conclusions: citrate supplements vary widely in their cost and citrate content. Patients and providers may find this information useful depending on their individual preferences for cost and pill size. Pharmaceutical Urocit-K was not the most cost-effective option; however, it may be the more convenient option as it requires fewer pills.
citrate tolerance
Calif Med 1950 Dec;73(6):494-6.PMID:14792339doi
There is a wide variation among human beings in tolerance to sodium citrate. It is important to those concerned with blood transfusions that the incidence of reactions to citrate is quite low, except in the event of massive transfusing, when the amount of citrate with the blood being given to the patient must be carefully considered.