6H05 (TFA)
目录号 : GC60533
An allosteric inhibitor of oncogenic K-Ras(G12C)
Cas No.:2061344-88-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
The Ras family of small GTPases (H-Ras, K-Ras, and N-Ras) function as molecular switches, cycling between a GTP-bound active state and a GDP-bound inactive state, to turn on downstream Raf protein kinases. This initiates complex signaling pathways involved in cell growth, differentiation, and apoptosis. Mutations leading to aberrant Ras activation are frequently associated with various human cancers. 6H05 is a small molecule that allosterically binds to a mutant cysteine on oncogenic K-Ras(G12C), thus inhibiting its function.1 Binding of 6H05 to K-Ras(G12C) disrupts both switch-I and switch-II, altering the native nucleotide preference to favor GDP over GTP, which impedes binding to Raf.1 Because 6H05 is selective for mutant Cys-12, it does not affect wild-type K-Ras.1
1.Ostrem, J.M., Peters, U., Sos, M.L., et al.K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactionsNature503(7477)548-551(2013)
| Cas No. | 2061344-88-3 | SDF | |
| Canonical SMILES | O=C(C1CCN(C(CSC2=CC=C(Cl)C=C2)=O)CC1)NCCSSCCN(C)C.O=C(O)C(F)(F)F | ||
| 分子式 | C22H31ClF3N3O4S3 | 分子量 | 590.14 |
| 溶解度 | DMSO: ≥ 51 mg/mL (86.42 mM) | 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 | 1.6945 mL | 8.4726 mL | 16.9451 mL |
| 5 mM | 0.3389 mL | 1.6945 mL | 3.389 mL |
| 10 mM | 0.1695 mL | 0.8473 mL | 1.6945 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。
Trans-Fatty Acid (TFA) elimination in Pakistan: A situational analysis
J Pak Med Assoc 2020 May;70(Suppl 2)(5):S1-S30.PMID:33144736doi
Recent research studies have highlighted that the consumption of industrially produced trans-fatty acids (TFAs) causes detrimental effects on human health. The World Health Organization (WHO) has recommended the elimination of TFA from diets to reduce the risk of non-communicable diseases (NCDs). In this paper, we use WHO's REPLACE framework for a situation analysis of TFAs in Pakistan's context by reviewing the literature on its dietary and industrial sources along with the legislative and regulatory context surrounding TFA related affairs in Pakistan. To maintain the authenticity of the data and the various actions implemented in Pakistan, we interviewed government officials, experts and researchers engaged in this field. By combining this information with a review of effective policies and best practices applied for TFA elimination around the world, we have prepared recommendations for policymakers in the country. The primary dietary sources of TFA in Pakistan are vanaspati ghee (partially hydrogenated vegetable oil), kinds of margarine, bakery shortenings and fat spreads. Whereas, their main producers are the edible oil, margarine, bakery and confectionary industries. Federal and provincial governments have introduced TFA regulations, but these vary across jurisdictions, complicating enforcement. Lack of credible penalties for violation of regulations, low public awareness and capacity and data gaps among regulators also inhibit TFA elimination. We recommend multi-stakeholder efforts for harmonization of mandatory TFA limits and labeling, replacement of traditional vanaspati ghee, communication efforts for behavioral change, promotion of replacement oils and strengthening regulators' assessment capacities.
TFA-Net: A Deep Learning-Based Time-Frequency Analysis Tool
IEEE Trans Neural Netw Learn Syst 2022 Mar 21;PP.PMID:35312624DOI:10.1109/TNNLS.2022.3157723.
Recently, synchrosqueenzing transform (SST)-based time-frequency analysis (TFA) methods have been developed for achieving the highly concentrated TF representation (TFR). However, SST-based methods suffer from two drawbacks. The first one is that the TFRs are unsatisfactory when dealing with the multicomponent signals, the instantaneous frequencies (IFs) of which are closely adjacent or intersected. Besides, the exhaustive adjustment of window length is required for SST-based methods to obtain the optimal TFR. To tackle these problems, in this article, we first analyze the concentration of TFRs for SST-based methods. A deep learning (DL)-based end-to-end replacement scheme for SST-based methods, named TFA-Net, is then proposed, which learns complete basis functions to obtain various TF characteristics of time series. The 2-D filter kernels are subsequently used for energy concentration. Different from the two-step SST-based methods where the TF transform and energy concentration are separated, the proposed end-to-end architecture makes the basis functions used for extracting TF features more beneficial to energy concentration. The comprehensive numerical experiments are conducted to demonstrate the effectiveness of the TFA-Net. The applications of the proposed method to real-world vital signs, undersea voices and micro-Doppler signatures show its great potential in analyzing nonstationary signals.
Development of a theory-informed questionnaire to assess the acceptability of healthcare interventions
BMC Health Serv Res 2022 Mar 1;22(1):279.PMID:35232455DOI:10.1186/s12913-022-07577-3.
Background: The theoretical framework of acceptability (TFA) was developed in response to recommendations that acceptability should be assessed in the design, evaluation and implementation phases of healthcare interventions. The TFA consists of seven component constructs (affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy) that can help to identify characteristics of interventions that may be improved. The aim of this study was to develop a generic TFA questionnaire that can be adapted to assess acceptability of any healthcare intervention. Methods: Two intervention-specific acceptability questionnaires based on the TFA were developed using a 5-step pre-validation method for developing patient-reported outcome instruments: 1) item generation; 2) item de-duplication; 3) item reduction and creation; 4) assessment of discriminant content validity against a pre-specified framework (TFA); 5) feedback from key stakeholders. Next, a generic TFA-based questionnaire was developed and applied to assess prospective and retrospective acceptability of the COVID-19 vaccine. A think-aloud method was employed with two samples: 10 participants who self-reported intention to have the COVID-19 vaccine, and 10 participants who self-reported receiving a first dose of the vaccine. Results: 1) The item pool contained 138 items, identified from primary papers included in an overview of reviews. 2) There were no duplicate items. 3) 107 items were discarded; 35 new items were created to maximise coverage of the seven TFA constructs. 4) 33 items met criteria for discriminant content validity and were reduced to two intervention-specific acceptability questionnaires, each with eight items. 5) Feedback from key stakeholders resulted in refinement of item wording, which was then adapted to develop a generic TFA-based questionnaire. For prospective and retrospective versions of the questionnaire, no participants identified problems with understanding and answering items reflecting four TFA constructs: affective attitude, burden, perceived effectiveness, opportunity costs. Some participants encountered problems with items reflecting three constructs: ethicality, intervention coherence, self-efficacy. Conclusions: A generic questionnaire for assessing intervention acceptability from the perspectives of intervention recipients was developed using methods for creating participant-reported outcome measures, informed by theory, previous research, and stakeholder input. The questionnaire provides researchers with an adaptable tool to measure acceptability across a range of healthcare interventions.
Trans fatty acids (TFA): analysis, occurrence, intake and clinical relevance
Eur J Med Res 2003 Aug 20;8(8):358-62.PMID:12915330doi
More than one quarter of total daily calories are normally provided by fatty acids which contain at least one double bond. The usual configuration of these double bonds is the cis configuration. Trans fatty acids (TFA) are formed in technological and microbiological processes by isomerization of cis double bonds to trans double bonds. In the 1990s, there was public health concern about epidemiological studies suggesting that TFA increase the risk of coronary heart disease. High intakes of TFA may have an influence on total cholesterol and other blood parameters; but on the other hand there have been a lot of studies which have not been able to confirm these results. TFA are formed in varying amounts during the industrial hydrogenation of vegetable oils and in the first stomach of ruminants. Regular margarines contain varying contents of partially hydrogenated vegetable oils, and therefore of TFA. The main dietary TFA are the trans octadecenoic acids, which contribute to approximately 80-90 % of total TFA content in foods. The predominant isomer of milk fat is trans vaccenic acid, which is directly influenced by ruminant feeding conditions. For a reliable identification and quantification of TFA in foods and other biological matrices it is necessary to use a combination of chromatographic methods (GC-FID, GC-MS, GC-FTIR, Ag superset +-HPLC).
Diprotin A TFA Exerts Neurovascular Protection in Ischemic Cerebral Stroke
Front Neurosci 2022 May 9;16:861059.PMID:35615279DOI:10.3389/fnins.2022.861059.
Background: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved β-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods: C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 μg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results: Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion: Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced β-catenin cleavage to protect blood vessels.