G-1
目录号 : GC12766
G-1 is a selective and potent agonist of GPR30 with EC50 value about 2 nM.
Cas No.:881639-98-1
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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
A549 human lung cancer cells |
|
Preparation Method |
A549 human lung cancer cells were treated with various concentrations (10-8, 10-7, 10-6, 10-5 and 10-4 M) of 17β-estradiol and G-1 in 96-well plates and incubated for 48 or 72 h. Following incubation, MTT solution (Sigma-Aldrich) was added to each well at a concentration of 0.5 mg/ml, and incubated for 4 h at 37°C. |
|
Reaction Conditions |
0.01-100 µM for 48 and 72 h |
|
Applications |
Treatment with G-1 (10-5 and 10-4 M) for 48 and 72 h significantly decreased cell proliferation. |
| Animal experiment [2]: | |
|
Animal models |
SJL mice (5-7 weeks old) |
|
Preparation Method |
SJL mice were immunized s.c. with 50 µg PLP139-151 and CFA (400 µg Mycobacterium tuberculosis). Mice were treated with 50 mg/kg/day G-1 daily for 21 days beginning at the day of disease induction. Control mice were similarly treated with vehicle (5% Dimethyl sulfoxide (DMSO), 95% Polyethylene glycol (PEG)-300. |
|
Dosage form |
50 mg/kg/day for 21 days |
|
Applications |
G-1 administration significantly reduced the severity of actively induced experimental allergic encephalomyelitis (EAE) but not the incidence of disease. |
|
References: [1]: Kurt A H, Çelik A, Kelleci B M. Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells[J]. Oncology Letters, 2015, 10(5): 3177-3182. | |
G-1 is a selective and potent agonist of GPR30 with EC50 value about 2 nM [1].
G-1 treatment (10-5 and 10-4 M) for 48 and 72 h significantly decreased A549 cell proliferation, at 72 h, the IC50 value for G-1 was calculated to be 2×10-5 M [2]. G-1 treatment at a concentration of 2×10-5 M had no significant effect on CAT activity but led to a significant increase in SOD activity, GPx activity and NO level [2]. G-1 inhibited TNF-α and IL-6 release on primary human macrophages derived from monocytes treated with GM-CSF over 6 days. The agonist inhibited the induction of both cytokines with IC50 values of 209 nM and 317 nM, respectively [3]. G-1 was also able to inhibit LPS induction of TNF-α in a mouse macrophage cell line, RAW 264.7 [3].
G-1 (50 mg/kg/day, 21 days) administration significantly reduced the severity of actively induced experimental allergic encephalomyelitis (EAE). G-1 treatment reduced the qualitative degree of inflammation in the lumbar spinal cord. G-1 treatment reduced the fraction of CNS-infiltrating macrophages (CD45hiCD11b+) in three individually analyzed mice [3]. G-1 could exert protective effects on motoneurons. The intraperitoneal injection of the GPR30 agonist G-1 for 14 days induces neuroprotective effects similar with the same dose of E2 [4].
References:
[1]. Bologa C G, Revankar C M, Young S M, et al. Virtual and biomolecular screening converge on a selective agonist for GPR30[J]. Nature chemical biology, 2006, 2(4): 207-212.
[2]. Kurt A H, Çelik A, Kelleci B M. Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells[J]. Oncology Letters, 2015, 10(5): 3177-3182.
[3]. Blasko E, Haskell C A, Leung S, et al. Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis[J]. Journal of neuroimmunology, 2009, 214(1-2): 67-77.
[4]. Cheng Q, Meng J, Wang X, et al. G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice[J]. Bioscience Reports, 2016, 36(4).
| Cas No. | 881639-98-1 | SDF | |
| 化学名 | rel-1-[4-(6-bromo-1,3-benzodioxol-5-yl)-3aR,4S,5,9bS-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone | ||
| Canonical SMILES | CC(C1=CC([C@@](C=CC2)([H])[C@@]2([H])[C@H](C3=CC(OCO4)=C4C=C3Br)N5)=C5C=C1)=O | ||
| 分子式 | C21H18BrNO3 | 分子量 | 412.28 |
| 溶解度 | 1mg/ml in ethanol; 20mg/ml in DMSO; 30mg/ml in DMF | 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。 |
||
| 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 | 2.4255 mL | 12.1277 mL | 24.2554 mL |
| 5 mM | 0.4851 mL | 2.4255 mL | 4.8511 mL |
| 10 mM | 0.2426 mL | 1.2128 mL | 2.4255 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 G-Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Proliferation and Causes Apoptosis in Leukemia Cell Lines of T Lineage
Front Cell Dev Biol2022 Feb 14;10:811479.PMID: 35237599DOI: 10.3389/fcell.2022.811479
The G-protein-coupled estrogen receptor (GPER) mediates non-genomic action of estrogen. Due to its differential expression in some tumors as compared to the original healthy tissues, the GPER has been proposed as a therapeutic target. Accordingly, the non-steroidal GPER agonist G-1, which has often demonstrated marked cytotoxicity in experimental models, has been suggested as a novel anticancer agent for several sensitive tumors. We recently revealed that cell lines derived from acute T-cell (query) lymphoblastic leukemia (T-ALL) express the GPER. Here, we address the question whether G-1 is cytotoxic to T-ALL. We have shown that G-1 causes an early rise of intracellular Ca2+, arrests the cell cycle in G2/M, reduces viability, and provokes apoptosis in T-ALL cell lines. Importantly, G-1 caused destabilization and depolymerization of microtubules. We assume that it is a disturbance of the cytoskeleton that causes G-1 cytotoxic and cytostatic effects in our model. The observed cytotoxic effects, apparently, were not triggered by the interaction of G-1 with the GPER as pre-incubation with the highly selective GPER antagonist G-36 was ineffective in preventing the cytotoxicity of G-1. However, G-36 prevented the intracellular Ca2+ rise provoked by G-1. Finally, G-1 showed only a moderate negative effect on the activation of non-leukemic CD4+ lymphocytes. We suggest G-1 as a potential antileukemic drug.
Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma
Int J Mol Sci2022 Nov 18;23(22):14309.PMID: 36430793DOI: 10.3390/ijms232214309
Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio-chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.
Determination of Clonogenic Radiosensitivity of HeLa Cells in Early and Late G1 Phases
Anticancer Res2022 Nov;42(11):5407-5413.PMID: 36288874DOI: 10.21873/anticanres.16045
Background/aim: Using a fluorescent ubiquitination-based cell cycle indicator (Fucci), we recently reported that post irradiation of HeLa cells, micronuclei frequency increased in the early G1 phase in comparison with that in the late G1 phase. This is inconsistent with the results of well-recognized studies that used clonogenic assays. In this study, we determined radiosensitivity of the cells using a clonogenic assay by making the best use of the Fucci property, while simultaneously characterizing cell cycle kinetics and DNA damage responses.
Materials and methods: Early and late G1 phase cell fractions were isolated using a cell sorter by exploiting the different red fluorescence intensities of Fucci. Radiosensitivity was determined by the colony formation assay. Time-lapse imaging and immunostaining were performed to analyze cell cycle kinetics and DNA damage.
Results: Late G1 cells were more radioresistant than early G1 cells. Cells irradiated in the early and late G1 phases induced G2 arrest, while the latter demonstrated a significantly longer duration of G2 arrest. This difference became more evident as the radiation dose increased. Furthermore, 16 h after irradiation, a greater number of γH2AX foci remained in cells irradiated in the early G1 phase than in those irradiated in the late G1 phase.
Conclusion: HeLa cells in the late G1 phase are more radioresistant than those in the early G1 phase, presumably because DNA damage is efficiently repaired during a longer G2 arrest in late G1 cells.
Interaction of aflatoxin G1 with free DNA in vitro and possibility of its application in removing aflatoxin G1
J Environ Sci Health B2021;56(10):932-940.PMID: 34554053DOI: 10.1080/03601234.2021.1979838
The present study sought to evaluate the interaction between aflatoxin G1 and free DNA in vitro through different analytical techniques. The UV-visible spectra results showed that the structure of DNA might be changed with a new aflatoxin G1-DNA complex forming, which indicated that the interacting mode between them was the intercalating mode. The DNA melting temperature increased by 12.80 °C, suggesting that the DNA double helix structure was more compact and stable through intercalation. The circular dichroism (CD) spectra results indicated that the interaction of aflatoxin G1 with DNA induced the DNA base stacking changes. The results of agarose gel electrophoresis and fluorescence microscope further verified that the interacting mode between aflatoxin G1 and DNA was intercalation mode. According to the fluorescence spectrum data, the binding constant was calculated 6.24 × 104 L·mol-1. The thermodynamic results demonstrated that the reaction of aflatoxin G1 intercalating to DNA was a spontaneous reaction. The elimination results suggested that aflatoxin G1 could be enriched and removed by DNA intercalation through magnetic beads separation, with the removal efficiency of 93.73%. The study results would provide a theoretical basis for establishing a new aflatoxin removal method based on DNA intercalation.
Final checkup of neoplastic DNA replication: evidence for failure in decision-making at the mitotic cell cycle checkpoint G(1)/S
Exp Hematol2008 Nov;36(11):1403-16.PMID: 18940520DOI: 10.1016/j.exphem.2008.07.009
Objectives: Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Further analyses of cycle progression will open up new approaches in antineoplastic therapy.
Materials and methods: The following bibliographic databases were consulted: Central Medical Library Cologne, PubMed (English), the last search was done on April 23,2008 and key words searched were: cell cycle, cell memory, DNA methylation, embryonal/neoplastic stem cells, enzyme-modulated chromatin, G(1)-G(1)/S checkpoint, genomic/epigenomics, genomic viral DNA, histones, telomere/telomerases, transcription factors, neoplastic transformation, senescence.
Results: Gene transcription and epigenomic surveillance form a functional entity. In proliferation programs, transcriptional information is mediated by chromatin and DNA methylation, analyzed and processed in G(1) phase, and converged on the parental checkpoint G(1)/S for final decision-making on DNA replication. Genomic reorientation appears to be associated with transcriptional instability, which normally is corrected, possibly during the G(2)/M phase, to new levels of epigenomic equilibria. We speculate that daughter stem cells inherit persistent neoplasm-specific transcriptional instabilities through failure of the parental G(1)/S checkpoint. Foreign, silenced, potentially oncogenic DNA sequences, i.e. regular components of the human genome such as endogenous retroviruses, could conceivably be activated for expression in neoplastic transformation by epigenomic histone deacetylase/acetyl transferase/histone methyltransferase-mixed lineage leukemia deregulations.
Conclusions: Failure of cell cycle G(1)/S decision-making for DNA replication is the final and possibly a major cause in neoplastic transformation. Therefore, further analysis of the dynamics of G(1)-G(1)/Sphases could provide new opportunities for therapeutic strategies.