TM-1
目录号 : GC65502
TM-1 是丙酮酸脱氢酶激酶 (PDHK) 的强效抑制剂。TM-1 抑制 PDHK1 和 PDHK2 的活性，IC50 分别为2.97 μM 和 5.2 μM。TM-1 能够阻断丙酮酸脱氢酶复合物 (PDHC) 磷酸化，并抑制癌细胞增殖。
Cas No.:921099-13-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
TM-1 is a potent inhibitor of pyruvate dehydrogenase kinase (PDHK1). TM-1 inhibits PDHK1 and PDHK2 with IC50s of 2.97 μM and 5.2 μM, respectively. TM-1 blocks pyruvate dehydrogenase complex (PDHC) phosphorylation, and inhibits cell proliferation[1].
TM-1 (0-10 μM) inhibits PDHK1 activity with the inhibition rate of 80.5% (dosage at 10 μM) and an IC50 value of 2.97 μM[1].TM-1 (0-2.1 μM; 12 h) shows anti-osteosarcoma activity and inhibits MG-63 cells with an EC50 value of 14.5 μM[1].TM-1 (3, 6, 12 μM; 24 h) decreases PDHC phosphorylation of both Ser293 and Ser232 sites in a dose-dependent manner[1].
[1]. Fang A, et al. Identification of pyruvate dehydrogenase kinase 1 inhibitors with anti-osteosarcoma activity. Bioorg Med Chem Lett. 2017 Dec 15;27(24):5450-5453.
| Cas No. | 921099-13-0 | SDF | Download SDF |
| 分子式 | C26H32N2O6 | 分子量 | 468.54 |
| 溶解度 | 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 | 2.1343 mL | 10.6714 mL | 21.3429 mL |
| 5 mM | 0.4269 mL | 2.1343 mL | 4.2686 mL |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1343 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 |
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| % 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。
Mechanisms of tomato mosaic virus RNA replication and its inhibition by the host resistance factor TM-1
Curr Opin Virol 2014 Dec;9:8-13.PMID:25212767DOI:10.1016/j.coviro.2014.08.005.
In the plant immune system, sensor proteins encoded by dominant resistance genes activate a defense response upon pathogen infection. The tomato mosaic virus (ToMV) resistance gene TM-1 is exceptional in that it inhibits ToMV multiplication without inducing a defense response. Several lines of evidence had suggested that TM-1 encodes a direct inhibitor of ToMV RNA replication. The TM-1 gene product was identified by purification of an inhibitor protein using a cell-free translation and replication system for ToMV RNA. Further analyses using the system showed that TM-1 bound ToMV replication proteins, and that the Tm-1-bound ToMV replication proteins retained the ability to bind membranes, while TM-1 inhibited replication complex formation on the membranes.
Dexamethasone increases Cdc42 expression in human TM-1 cells
Curr Eye Res 2015 Mar;40(3):290-9.PMID:24871483DOI:10.3109/02713683.2014.922191.
Purpose: Changes in the cytoskeletal organization of the human trabecular meshwork (HTM) is thought to be responsible for primary open-angle glaucoma (POAG) pathologies. Cdc42 is a Rho GTPase; Rho GTPases are important modulatory agents of the cytoskeleton. This study aimed to investigate the effects of dexamethasone (DEX) on Cdc42 in a transformed HTM cell line, TM-1 to understand the molecular pathologies underlying POAG. Methods: TM-1 cells were cultured in vitro. The cultures were treated with DEX at 10(-6) and 10(-7) M for 1-4 days. Cdc42 was silenced using small interfering RNA (siRNA). The expression levels of Cdc42 in the TM-1 cells were measured using reverse transcription (RT)-PCR, western blotting analysis and immunofluorescence. Its downstream effectors, p21-activated kinase phosphorylation (phospho-PAK) and myosin light chain kinase (MLCK), were measured using western blotting analysis. In addition, the F-actin of TM-1 cells was stained using phalloidin. Results: The mRNA and protein levels of Cdc42 showed an increase in TM-1 cells with DEX treatment and a decrease in TM-1 cells transfected with Cdc42 siRNA. Moreover, phospho-PAK levels increased, whereas MLCK levels appeared to decrease, with DEX treatment. The F-actin of DEX-treated TM-1 cells displayed a rearrangement. Cdc42 siRNA decreased the expression of Cdc42 and its related proteins, resulting in an attenuation of the effects of DEX on Cdc42 and F-actin organization in TM-1 cells. Conclusions: DEX increases Cdc42 expression in TM-1. This may represent a potential mechanism of DEX-induced HTM cytoskeletal rearrangement.
Characterization of TM-1 gene action on replication of common isolates and a resistance-breaking isolate of TMV
Virology 1987 Dec;161(2):527-32.PMID:3686829DOI:10.1016/0042-6822(87)90147-4.
TM-1 is a gene which confers resistance to infection, in tomatoes, by tobacco mosaic virus (TMV). To investigate the biochemical mechanism of the resistance, we have established cell suspensions of three lines of tomatoes, i.e., +/+ (susceptible, wild-type, no TM-1 gene), TM-1/+ (heterozygous for the TM-1 gene), and TM-1/TM-1 (homozygous for the TM-1 gene). Protoplasts isolated from these cells were inoculated with RNA of the tomato strain L and Lta1 (a resistance-breaking strain which was recently isolated spontaneously from L) of TMV by means of electrophoration. The syntheses of all viral-coded proteins and TMV-specific RNAs could be detected in L-inoculated +/+ and Lta1-inoculated +/+, TM-1/+, TM-1/TM-1 protoplasts, while their production was markedly reduced in L-inoculated TM-1/+ protoplasts. L strain could multiply in TM-1/+ protoplasts to a greater extent with less delay when a large amount of inoculum RNA was used. However, viral production was completely blocked in TM-1/TM-1 protoplasts even when a large amount of L-RNA was used for inoculation.
Expression of 14-3-3 Zeta Protein in Dexamethasone-Treated Mice and Human TM-1 Cells
Curr Eye Res 2017 Aug;42(8):1124-1129.PMID:28494163DOI:10.1080/02713683.2017.1284242.
Purpose: 14-3-3 zeta protein plays a potential protective role in neurodegenerative disease. Given that glaucoma and neurodegenerative diseases share a similar pathogenesis, it is possible that 14-3-3 zeta may have a similar protective effect in the glaucomatous process. In the present study, we measured the expression of 14-3-3 zeta in vivo (mouse eyes) and in vitro in a transformed human trabecular meshwork (HTM) cell line, TM-1, and assessed the possible roles of this protein in dexamethasone (DEX)-treated eyes and HTM cells. Methods: Mouse eyes were randomly treated with 0.1% dexamethasone (DEX) eye drops or phosphate-buffered solution (PBS) for 28 days. The expression and distribution of 14-3-3 zeta protein in mouse eyes were examined using immunofluorescence. TM-1 cells were treated with DEX (10-6 or 10-7 M) or PBS for 1, 4, or 7 days, and the mRNA and protein expression of 14-3-3 zeta were detected by real-time RT-PCR and Western blotting. Results: 14-3-3 zeta protein was highly expressed in the mouse cornea, trabecular meshwork (TM), and ciliary body. Intraocular pressure (IOP) was significantly elevated, whereas the 14-3-3 zeta expression was significantly decreased in mouse TM after 0.1% DEX treatment for 28 days. In vitro, treatment with 10-7 M DEX mildly increased 14-3-3 zeta mRNA and protein expression (p > 0.05), whereas 10-6 M DEX significantly decreased expression of 14-3-3 zeta mRNA and protein (p < 0.05) compared to the control (Ctrl) group at the seventh day. Conclusions: DEX can increase IOP in mouse eyes and concurrently downregulate 14-3-3 zeta protein expression in mouse TM. The effects of DEX on 14-3-3 zeta expression in vitro were both dose- and time-related. Our results suggest that alterations in 14-3-3 zeta protein may be implicated in DEX-induced pathological elevated IOP.
Characterization of Developmental Immature Fiber ( im) Mutant and Texas Marker-1 (TM-1) Cotton Fibers Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy
Appl Spectrosc 2017 Jul;71(7):1689-1695.PMID:28106475DOI:10.1177/0003702816684639.
The immature fiber ( im) mutant is one type of cotton fiber mutant with unique characteristics of non-fluffy cotton bolls. Compared to its near-isogenic wild type Texas Marker-1 (TM-1), im fiber has a thin secondary cell wall and is less mature. In this work, we applied the previously proposed principal component analysis (PCA) and simple algorithms to analyze the attenuated total reflection Fourier transform infrared (ATR FT-IR) spectra of developmental im and TM-1 fibers. The results from these approaches could not effectively and consistently indicate the inherent difference between TM-1 and im fibers at the same developmental stage. The difference between TM-1 and corresponding im fibers was detected when comparing the normalized intensity variations of the 730 cm-1 bands. The 730 cm-1 band intensities in developmental im fibers are temporally lower than those in developmental TM-1 fibers although they became similar when the TM-1 and im fibers are fully mature. The observation might imply the likelihood of temporal reduction of amorphous regions in developmental im fibers rather than in developmental TM-1 fibers.