C29
(Synonyms: TLR2-IN-C29) 目录号 : GC33820
C29 是一种 Toll 样受体 2 (TLR2) 抑制剂。
Cas No.:363600-92-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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| Cell experiment [1]: | |
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Cell lines |
HEK-Blue cells,RAW macrophages,THP-1 macrophages |
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Preparation Method |
C29 were dissolved in DMSO as 50mM stock solution. Final DMSO concentrations in cell culture were below 0.2% (v/v). The cells were first incubated with the C29 for 1h and afterwards stimulated with the respective TLR(Toll like receptor) agonist. |
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Reaction Conditions |
0.01µM, 0.1µM, 1µM, 10µM 100µM for 1 hour |
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Applications |
C29 showed inhibit affection for TLR2/1 or TLR2/6 (IC50 21µM and 23µM). |
| Animal experiment [2]: | |
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Animal models |
Female C57BL/6J mice |
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Preparation Method |
C29 was dissolved and diluted in solution (10% DMSO/40% PEG300/5% Tween-80/45% saline), then injected intraperitoneally (1.3 µmol/g) 1 h before HBeAg treatment, with the same volume of dissolving reagent as the vehicle group. |
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Dosage form |
Intraperitoneal injection, 1.3 µmol/g |
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Applications |
To verify the roles of TLR-2 in vivo, mice were pretreated with C29 before the administration of HBeAg. The expression of IL-6, TNF-α, and CCL-2 was significantly alleviated, but IL-10 was upregulated in the liver. |
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References: [1]: Grabowski, M.; Murgueitio, M.S.; Bermudez, M.; Wolber, G.; Weindl, G. The novel small-molecule antagonist MMG-11 preferentially inhibits TLR2/1 signaling. Biochem. Pharmacol. 2020, 171, 113687. | |
C29 is a Toll-like receptor 2 (TLR2) inhibitor. C29, inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles [1].
C29 inhibited TLR2/1-mediated NF-κB activation (IC50 0.87μM), and inhibited TLR2/6 heterodimer with IC50 23μM [2]. C29 and o-vanillin may function by specifically targeting the BB loop pocket of the TLR2 TIR domain, altering its function and/or position [1].
Mice were pretreated with C29 before the administration of hepatitis B e antigen (HBeAg), to verify the roles of TLR-2 in vivo, the expression of IL-6, TNF-α, and CCL-2 was significantly alleviated, but IL-10 was upregulated in the liver [3]. C29 did not affect lipid accumulation, but the adipogenesis inhibitory effects of exopolysaccharide (EPS) significantly decreased in the C29-treated group. The results showed that activation of the AMPK signalling pathway by EPS was inhibited in the early stage (day 4) of adipogenic differentiation, when TLR2 and myeloid differentiation primary response 88 (MyD88) expression is inhibited by C29, indicating that EPS activates the AMPK signalling pathway by interacting with TLR2, consequently inhibiting adipogenesis [4].
References:
[1]. Mistry P, Laird MH, Schwarz RS, Greene S, Dyson T, Snyder GA, et al. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain. Proc Natl Acad Sci U S A (2015) 112(17):5455-60. doi:10.1073/pnas.1422576112
[2]. Grabowski, M.; Murgueitio, M.S.; Bermudez, M.; Wolber, G.; Weindl, G. The novel small-molecule antagonist MMG-11 preferentially inhibits TLR2/1 signaling. Biochem. Pharmacol. 2020, 171, 113687.
[3]. Xie X, Lv H, Liu C, Su X, Yu Z, Song S, et al. HBeAg Mediates Inflammatory Functions of Macrophages by TLR2 Contributing to Hepatic Fibrosis. BMC Med (2021) 19:247. doi: 10.1186/s12916-021-02085-3
[4]. Lee, J.; Park, S.; Oh, N.; Park, J.; Kwon, M.; Seo, J.; Roh, S. Oral intake of Lactobacillus plantarum L-14 extract alleviates TLR2-and AMPK-mediated obesity- associated disorders in hight-fat-diet-induced obese C57BL/6J mice. Cell Prolif. 2021, 54, e13039
C29 是一种 Toll 样受体 2 (TLR2) 抑制剂。 C29 在人 HEK-TLR2 和 THP-1 细胞中抑制由合成和细菌 TLR2 激动剂诱导的 TLR2/1 和 TLR2/6 信号传导，但仅抑制小鼠巨噬细胞中的 TLR2/1 信号传导。 C29 未能抑制由其他 TLR 激动剂和 TNF-α 诱导的信号传导。 BB 环袋残基的诱变揭示了 TLR2/1 而非 TLR2/6 信号传导不可或缺的作用，表明不同的作用[1]。
C29 抑制 TLR2/1 介导的 NF-κB 激活（IC50 0.87μM），并抑制 TLR2/6 异二聚体，IC50 23μM [2 ]。 C29 和 o-香兰素可能通过特异性靶向 TLR2 TIR 结构域的 BB 环口袋、改变其功能和/或位置[1] 发挥作用。
小鼠在给予乙型肝炎e抗原（HBeAg）之前用C29预处理，以验证TLR-2在体内的作用，IL-6、TNF-α和CCL-2的表达显着减轻，但 IL-10 在肝脏中上调 [3]。 C29 不影响脂质积累，但胞外多糖 (EPS) 的脂肪形成抑制作用在 C29 处理组中显着降低。结果表明，EPS 对 AMPK 信号通路的激活在成脂分化的早期（第 4 天）受到抑制，此时 TLR2 和髓系分化初级反应 88（MyD88）的表达被 C29 抑制，表明 EPS 激活 AMPK 信号通路通路通过与 TLR2 相互作用，从而抑制脂肪生成[4]。
| Cas No. | 363600-92-4 | SDF | |
| 别名 | TLR2-IN-C29 | ||
| Canonical SMILES | OC1=C(/C=N/C2=C(C)C(C(O)=O)=CC=C2)C=CC=C1OC | ||
| 分子式 | C16H15NO4 | 分子量 | 285.29 |
| 溶解度 | DMSO : ≥ 30 mg/mL (105.16 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 | 3.5052 mL | 17.526 mL | 35.0521 mL |
| 5 mM | 0.701 mL | 3.5052 mL | 7.0104 mL |
| 10 mM | 0.3505 mL | 1.7526 mL | 3.5052 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。
The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags
Chem Commun (Camb) 2021 Oct 12;57(81):10540-10543.PMID:34553712DOI:10.1039/d1cc04259a.
Anticancer drug development inspired by natural products based on protein-protein interactions (PPI) is a promising strategy. We developed structurally-simplified C29-C34 side-chain analogs of aplyronine A (ApA), an antitumor marine macrolide. Among them, the analog possessing the C23 acyloxy group, the C29 N,N-dimethyl-L-alanine ester and the C34 N-methyl enamide showed potent actin-depolymerizing activity. Binding kinetics, molecular docking, and affinity-purification experiments revealed that they are versatile actin-affinity tags to accelerate studies on the mode of action related to cytoskeletal dynamics and the development of PPI-based drug leads.
Lactobacillus plantarum C29 Alleviates TNBS-Induced Memory Impairment in Mice
J Microbiol Biotechnol 2018 Jan 28;28(1):175-179.PMID:29081213DOI:10.4014/jmb.1709.09042.
In a preliminary study, Lactobacillus plantarum C29 was found to suppress 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Therefore, to understand whether an anti-colitic probiotic C29 could attenuate memory impairment, we examined the effects of C29 on TNBS-induced memory impairment in mice. Orally administered Lactobacillus plantarum C29 attenuated TNBS-induced memory impairment in mice in the Y-maze, noble object, and passive avoidance task tests. C29 treatment increased TNBS-suppressed hippocampal brain-derived neurotrophic factor expression and inhibited TNBS-induced hippocampal NF-kappaB activation and blood LPS levels. Moreover, C29 restored the TNBS-disturbed gut microbiota composition. These findings suggest that C29 can alleviate memory impairment presumably by restoring the gut microbiota composition.
Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue
Acta Pharmacol Sin 2021 Jun;42(6):964-974.PMID:32934347DOI:10.1038/s41401-020-00524-0.
Beige adipocytes have been considered as a potential strategy in anti-obesity therapy because of its thermogenic capacity. AMP-activated protein kinase (AMPK) plays important roles in regulating adipose tissue function. C29 is a novel pyrazolone derivative with AMPK activity. In the current study, we investigated the role of C29 in the regulation of thermogenesis using differentiated adipocytes and diet-induced obese mice, and explored the mechanisms that might be involved in energy expenditure via adipocyte AMPK activation. We showed that treatment with C29 (2.5-10 μM) concentration-dependently increased thermogenesis in differentiated preadipocytes separated from inguinal white adipose tissue (iWAT), evidenced by increased expression levels of thermogenesis markers such as Ucp1, Pgc-1α, Dio2, Prdm16, Cox7a1, Cox8b, Elovl3, and Cidea, fatty acid oxidation (FAO) genes including Cpt1a, Lcad and Pparα, as well as beige-selective genes such as Cd137, Tmem26, Slc27a1, and Tbx1. In high-fat diet (HFD)-fed mice, oral administration of C29 (30 mg·kg-1·day-1) for 9 weeks alleviated HFD-induced obesity, promoted energy expenditure and modulated iWAT browning. However, these effects were not observed in adipose-specific AMPKα1/α2 knockout (AKO) mice following C29 administration. Together, this study demonstrates that C29 regulates energy balance via adipocyte AMPK. Our findings show that the discovery of AMPK activators that specifically target adipose tissue may have therapeutic potential for treating obesity-related metabolic diseases.
Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory impairment in Fischer 344 rats
Lett Appl Microbiol 2015 Apr;60(4):307-14.PMID:25598393DOI:10.1111/lam.12393.
To understand the anti-inflammaging effect of lactic acid bacteria, we selected NF-κB activation-inhibitory Lactobacillus pentosus var. plantarum C29 and investigated its memory-enhancing and anti-inflammatory effects in aged Fischer 344 rats. C29 (2 × 10(9) CFU rat(-1) ), which was orally administered once a day (6 days per week) for 8 weeks, significantly restored age-reduced spontaneous alternation to 95.2% of that seen in young rats (P < 0.05). C29 treatment also shortened the escape latency on the 4th day to 53.8% of that seen in young rats (P < 0.05). Twenty hours after the last training session, C29 significantly increased the swimming time within the platform quadrant, which was shortened in the aged control rats. Oral administration of C29 restored age-reduced doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) activation in aged rats. Treatment of aged rats with C29 suppressed the expression of p16, cyclooxygenase-2, and inducible nitric oxide synthase, as well as the activation of Akt, mTOR, and NF-κB in the hippocampus. These findings suggest that C29 ameliorates ageing-dependent memory impairment by inhibiting NF-κB signalling pathway, inducing DCX and BDNF expression and activating CREB. Significance and impact of the study: The anti-inflammatory Lactobacillus pentosus var. plantarum C29 had the memory-enhancing effect in aged Fischer 344 rats by restoring doublecortin and brain-derived neurotrophic factor expression and suppressing p16 expression and NF-κB activation in the brain. Therefore, C29 may be useful in ameliorating age-related degenerative dementia.
Lactobacillus pentosus var. plantarum C29 protects scopolamine-induced memory deficit in mice
J Appl Microbiol 2012 Dec;113(6):1498-506.PMID:22925033DOI:10.1111/j.1365-2672.2012.05437.x.
Aims: In the preliminary study, kimchi, a traditional food fermented with Chinese cabbage, protected scopolamine-induced mouse memory deficit in passive avoidance test. Therefore, we screened protective ingredients, particularly lactic acid bacteria, from Chinese cabbage kimchi against scopolamine-induced memory deficit in mice. Methods and results: Lactic acid bacteria, isolated from Chinese cabbage kimchi, were identified by 16S rDNA sequence analysis, G+C content and cellular fatty acid composition and sugar fermentation test. Memory deficit was induced in mice by intraperitoneally injecting with scopolamine. Kimchi, particularly its supernatant, protected scopolamine-induced memory deficit in mice in passive avoidance test. Of kimchi ingredients, a lactic acid bacterium, strain C29, potently protected scopolamine-induced memory deficit in mice. C29 was a gram-positive, catalase-negative, anaerobic and non-motile rod. Its pylogenetic property was near to Lactobacillus pentosus (99%) and Lact. plantarum (99%). However, C29 fermented inulin and L-rhamnose and grew in pH 3 and at 45°C in contrast with Lact. pentosus and Lact. plantarum. Therefore, it named to be Lact pentosus var. plantarum C29. The strain C29 protected scopolamine-induced memory deficit in Y-maze and Morris water maze tests. Furthermore, C29 increased hippocampal BDNF and p-CREB expressions, which were reduced by scopolamine. Conclusion: Lactobacillus pentosus var. plantarum C29 may protect memory deficit by inducing BDNF and p-CREB expressions. Significance and impact of the study: Lactic acid bacteria, such as Lact pentosus var. plantarum C29, may prevent memory deficit and its contained fermented foods may be beneficial for dementia.