Sorafenib (D4)
(Synonyms: Bay 43-9006-d4) 目录号 : GC37665
Sorafenib D4 (Bay 43-9006 D4) 是 Sorafenib 氘代化合物标准品。Sorafenib 是一种多激酶抑制剂，抑制 Raf-1，B-Raf 和 VEGFR-3 的 IC50 分别为6 nM，20 nM，22 nM。
Cas No.:1207560-07-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sorafenib D4 (Bay 43-9006 D4) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
[1]. Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109.
| Cas No. | 1207560-07-3 | SDF | |
| 别名 | Bay 43-9006-d4 | ||
| Canonical SMILES | O=C(C1=NC=CC(OC2=C([2H])C([2H])=C(NC(NC3=CC=C(Cl)C(C(F)(F)F)=C3)=O)C([2H])=C2[2H])=C1)NC | ||
| 分子式 | C21H12D4ClF3N4O3 | 分子量 | 468.85 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1329 mL | 10.6644 mL | 21.3288 mL |
| 5 mM | 0.4266 mL | 2.1329 mL | 4.2658 mL |
| 10 mM | 0.2133 mL | 1.0664 mL | 2.1329 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。
Hepatocellular carcinoma treatment over Sorafenib: epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?
Expert Opin Ther Targets 2015;19(12):1623-35.PMID:26212068DOI:10.1517/14728222.2015.1071354.
Introduction: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. Areas covered: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. Expert opinion: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the 'therapeutic stranding' of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its 'actors' (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.
Last line therapy with Sorafenib in colorectal cancer: A retrospective analysis
World J Gastroenterol 2016 Jun 21;22(23):5400-5.PMID:27340356DOI:10.3748/wjg.v22.i23.5400.
Aim: To analyze the efficacy of last line Sorafenib treatment in colorectal cancer patients. Methods: All patients receiving chemotherapy for colorectal cancer in the outpatient clinic of the University of Mainz since 2006 were retrospectively analyzed for last line Sorafenib exposure. Charts of identified patients were analyzed for clinic-pathological parameters, like data on gender, age, date of initial diagnosis, UICC stage, number and kind of the pre-therapies, therapy start and end of Sorafenib, Sorafenib mediated treatment cessation, side effects, response rates, time to progression and overall survival. Results: Ten patients with a median of 3.0 prior chemotherapy lines had received a last line Sorafenib therapy either alone (10%) or in combination with 5-fluorouracil derivates (90%). All patients suffered from colorectal cancer stage UICC 4 and were routinely seen in 2-wk intervals in the oncology outpatient clinic. Median duration of treatment was 142.0 d. At 8 wk 80% of patients showed stable disease but we did not observe any remissions. Median time to progression was 140.5 d (4.7 mo), while median overall survival reached 176.5 d. One patient ceased treatment due to side effects. Reason for treatment stop was bleeding complication in one case and non-specified Sorafenib intolerance in another case. Due to the retrospective approach we did not further quantify side effects. Conclusion: This retrospective analysis encourages further investigation of Sorafenib in colorectal cancer last line therapy.
Multidisciplinary management of hepatocellular carcinoma in clinical practice
Biomed Res Int 2014;2014:806391.PMID:24900987DOI:10.1155/2014/806391.
Background: Hepatocellular carcinoma (HCC) patients require different treatment strategies according to disease extension, liver function, and patient's fitness. We evaluated HCC multidisciplinary management in clinical practice. Methods: Consecutive patients were followed and treated with tailored medical, locoregional, and surgical treatments, according to disease stage and patient's fitness (age, Cumulative Illness Rating Scale (CIRS)). Activity, efficacy, and safety were evaluated. Results: Thirty-eight patients were evaluated: median age, 74; elderly 92%; CIRS secondary 28 (74%); Child-Pugh A 20 (53%), B 11 (29%); and Barcelona Clinic Liver Cancer (BCLC) 0 2 (5%), A 9 (24%), B 10 (26%), C 13 (34%), and D 4 (11%). Overall survival (OS) was 30 months. At 9 months median follow-up, among 25 unresectable HCC, OS was 10 months; BCLC B-D unfit for Sorafenib showed OS 3 months. Ten patients (40%) received Sorafenib: Child-Pugh A 5 (50%) and B 5 (50%) and disease control rate 89%, progression-free survival 7 months, and OS 9 months. G3-4 toxicities: anorexia, hypertransaminaemia, hyperbilirubinemia, and hypercreatininemia. Limiting toxicity syndromes were 40%, all multiple sites. Conclusion: HCC patients require multidisciplinary clinical management to properly select tailored treatments according to disease stage, fitness, and liver function. Patients suitable for Sorafenib should be carefully selected, monitored for individual safety, and prevalently characterized by limiting toxicity syndromes multiple sites.
Combining functional imaging and interstitial pressure measurements to evaluate two anti-angiogenic treatments
Invest New Drugs 2012 Feb;30(1):144-56.PMID:20924644DOI:10.1007/s10637-010-9543-y.
Background: Interstitial hypertension is responsible for poor capillary blood flow and hampered drug delivery. The efficacy of combined Sorafenib/bevacizumab treatment given according to different administration schedules has been evaluated by measuring both interstitial pressure (IP) and quantitative dynamic contrast-enhanced ultrasonography (DCE-US) parameters in melanoma-bearing mice. Material and methods: [corrected] Sixty mice were xenografted with B16F10 melanoma. Animals received a daily administration over 4 days (D0 to D3) of either Sorafenib at 30 mg/kg, bevacizumab at 2.5 mg/kg alone, or different schedules of combined treatments. Perfusion parameters determined using an Aplio® sonograph (Toshiba) with SonoVue® contrast agent (Bracco) were compared to IP measurements using fiberoptic probes (Samba®) at D0, D2, D4, D8. Results: The mean baseline IP values ranged between 6.55 and 31.29 mmHg in all the groups. A transient IP decrease occurred at D2 in all treated groups, and especially in the concomitant group which exhibited a significant IP reduction compared to D0. A significant decrease in both the peak intensity and the area under the curve was observed at D4 in the group with concomitant administration of both molecules which yielded maximal inhibition of the tumor volume and the number of vessels. No correlation was found between IP values and volume or perfusion parameters, indicating complex relationships between IP and vascularization. No IP gradients were found between the center and the periphery but IP values in these two regions were significantly correlated (R = 0.93). Conclusion: The results suggest that IP variations could be predictive of vascular changes and that one single IP measurement is sufficient to fully characterize the whole tumor.
Sunitinib in metastatic renal cell carcinoma: Experience from single center study, efficacy and safety
Indian J Cancer 2016 Jan-Mar;53(1):118-22.PMID:27146758DOI:10.4103/0019-509X.180844.
Background: The 5-year survival rate for metastatic renal cell carcinoma (RCC) is estimated to be <10%. RCC is highly resistant to chemotherapy. Targeted agents are now first choice of therapy for metastatic RCC such as sunitinib and Sorafenib. Methods: This study is a retrospective analysis of 15 patients having metastatic RCC treated with sunitinib. Apart from three patients, all had clear cell histology. Thirteen patients received dosage of 50 mg/d (4 weeks on/2 weeks off cycles). In 14 patients sunitinib was used as 1st line. The primary end point was objective response rate. Secondary end points were progression free survival (PFS) and safety. Results: Until date of reporting, 3 out of 15 patients are currently on sunitinib. The most common Memorial Sloan = Kettering Cancer Centre poor prognostic factor was an interval of <1 year between diagnosis and starting of treatment (80%). The objective response rate was 13.66% (complete response [CR] + partial response [PR] = 0 + 2). Clinical benefit rate (CR + PR + stable disease) was 60% (n = 9). Median PFS in this study was 7.5 months, with a range of 2-22 month. Median overall survival (OS) of patients in this study was 12 months with a range of 3-24 month. An impact of the dose or/and number of cycles on response was seen in this study, with patients having average cycles >3 showing better response rates, PFS and OS. Major toxicities seen were fatigue ( n= 7), diarrhea (n = 3) and skin rash (n = 4) with majority patients experienced Grade 1-2 toxicities. While Grade 3-4 toxicities include fatigue (n = 1), mucositis (n = 1) and nausea (n = 1). Conclusions: These results confirm efficacy and safety profile of sunitinib in metastatic RCC, particularly as a first line. Sunitinib produced a 60% disease control rate for metastatic RCC in Indian patients, with acceptable rates of toxicity at a dose of 50 mg daily. Response rates were well matched to other studies confirming the efficacy of sunitinib.