RCM-1
(Synonyms: 2-((2-氧代-2-(噻吩-2-基)乙基)硫基)-4,6-二(噻吩-2-基)吡啶-3-腈) 目录号 : GC33117
RCM-1 is a nontoxic inhibitor of Forkhead box M1 (FOXM1) that suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice. RCM-1 decreases carcinogenesis and nuclear β-catenin.
Cas No.:339163-65-4
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
Cell experiment: | Rd76-9 rhabdomyosarcoma, B16-FlO melanoma, H2122 lung adenocarcinoma, 4T1 breast carcinoma, MyC-CaP prostate carcinoma and KPC-2 pancreatic carcinoma cells are seeded in 6-well plates and incubated overnight. The cells are treated with 20 μM concentration of RCM-1 for 24, 48 and 72 h and cell growth is analyzed by counting alive cells using trypan blue. Cells treated with DMSO are used as controls[1]. |
Animal experiment: | Mice[1]Mouse Rd76-9 rhabdomyosarcoma cells (1×106 cells) are injected intramuscularly in the flanks of C56Bl/6J mice (n=8 mice per group). Seven days after the tumor cells inoculation, 40 μL of either Vehicle (DMSO) or RCM-1 (20 mg/kg body weight) are injected intraperitoneally in the animals every other day. The animals are sacrificed and tumors are harvested on day 16. RCM-1 treatment decreases Rd76-9 tumor growth as compared to the DMSO-treated group. Mouse B 16-FlO melanoma cells (1×106 cells) are injected subcutaneously in C56Bl/6J mice (n=7 animals per group). Three days after the tumor cell inoculation, 40 μL of either Vehicle (DMSO) or RCM1 (20 mg/Kg body weight) are injected intraperitoneally in the animals every other day. The animals are sacrificed and tumors are harvested on day 12[1]. |
References: [1]. ARYL SULFONOHYDRAZIDES.WO2018057550A1. | |
RCM-1 is a nontoxic inhibitor of Forkhead box M1 (FOXM1) that suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice. RCM-1 decreases carcinogenesis and nuclear β-catenin.
[1] Lifeng Sun, et al. Sci Signal. 2017 Apr 18;10(475):eaai8583. [2] Samriddhi Shukla, et al. Mol Cancer Ther. 2019 Jul;18(7):1217-1229.
| Cas No. | 339163-65-4 | SDF | |
| 别名 | 2-((2-氧代-2-(噻吩-2-基)乙基)硫基)-4,6-二(噻吩-2-基)吡啶-3-腈 | ||
| Canonical SMILES | N#CC1=C(C2=CC=CS2)C=C(C3=CC=CS3)N=C1SCC(C4=CC=CS4)=O | ||
| 分子式 | C20H12N2OS4 | 分子量 | 424.58 |
| 溶解度 | DMSO : 16.67 mg/mL (39.26 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 | 2.3553 mL | 11.7763 mL | 23.5527 mL |
| 5 mM | 0.4711 mL | 2.3553 mL | 4.7105 mL |
| 10 mM | 0.2355 mL | 1.1776 mL | 2.3553 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 FOXM1 Inhibitor RCM-1 Decreases Carcinogenesis and Nuclear β-Catenin
Mol Cancer Ther 2019 Jul;18(7):1217-1229.PMID:31040162DOI:10.1158/1535-7163.MCT-18-0709.
The oncogenic transcription factor FOXM1 has been previously shown to play a critical role in carcinogenesis by inducing cellular proliferation in multiple cancer types. A small-molecule compound, Robert Costa Memorial drug-1 (RCM-1), has been recently identified from high-throughput screen as an inhibitor of FOXM1 in vitro and in mouse model of allergen-mediated lung inflammation. In the present study, we examined antitumor activities of RCM-1 using tumor models. Treatment with RCM-1 inhibited tumor cell proliferation as evidenced by increased cell-cycle duration. Confocal imaging of RCM-1-treated tumor cells indicated that delay in cellular proliferation was concordant with inhibition of FOXM1 nuclear localization in these cells. RCM-1 reduced the formation and growth of tumor cell colonies in the colony formation assay. In animal models, RCM-1 treatment inhibited growth of mouse rhabdomyosarcoma Rd76-9, melanoma B16-F10, and human H2122 lung adenocarcinoma. RCM-1 decreased FOXM1 protein in the tumors, reduced tumor cell proliferation, and increased tumor cell apoptosis. RCM-1 decreased protein levels and nuclear localization of β-catenin, and inhibited protein-protein interaction between β-catenin and FOXM1 in cultured tumor cells and in vivo Altogether, our study provides important evidence of antitumor potential of the small-molecule compound RCM-1, suggesting that RCM-1 can be a promising candidate for anticancer therapy.
The ham-5, RCM-1 and rco-1 genes regulate hyphal fusion in Neurospora crassa
Microbiology (Reading) 2010 Sep;156(Pt 9):2621-2629.PMID:20522492DOI:10.1099/mic.0.040147-0.
Mutants of Neurospora crassa unable to participate in vegetative hyphal fusion (anastomosis) were isolated and characterized. From this analysis, three genes, RCM-1, rco-1 and ham-5, were identified and shown to be required for hyphal fusion. The RCM-1 and rco-1 genes are homologues of the Saccharomyces cerevisiae SSN6 and TUP1 genes, which encode a dimeric transcription factor in yeast. We demonstrate that in N. crassa the RCM-1 and rco-1 genes are required for hyphal fusion and normal hyphal morphology, and influence both asexual and sexual development. The ham-5 gene encodes a 1686 amino acid protein with two putative WD40 domains, which might participate in protein-protein interactions. ham-5 deletion mutants had a reduced rate of hyphal extension and altered hyphal morphology, and were unable to produce the conidial anastomosis tubes that are required for hyphal fusion during colony initiation.
Regulation of glycogen metabolism by the CRE-1, RCO-1 and RCM-1 proteins in Neurospora crassa. The role of CRE-1 as the central transcriptional regulator
Fungal Genet Biol 2015 Apr;77:82-94.PMID:25889113DOI:10.1016/j.fgb.2015.03.011.
The transcription factor CreA/Mig1/CRE-1 is a repressor protein that regulates the use of alternative carbon sources via a mechanism known as Carbon Catabolite Repression (CCR). In Saccharomyces cerevisiae, Mig1 recruits the complex Ssn6-Tup1, the Neurospora crassa RCM-1 and RCO-1 orthologous proteins, respectively, to bind to promoters of glucose-repressible genes. We have been studying the regulation of glycogen metabolism in N. crassa and the identification of the RCO-1 corepressor as a regulator led us to investigate the regulatory role of CRE-1 in this process. Glycogen content is misregulated in the rco-1(KO), RCM-1(RIP) and cre-1(KO) strains, and the glycogen synthase phosphorylation is decreased in all strains, showing that CRE-1, RCO-1 and RCM-1 proteins are involved in glycogen accumulation and in the regulation of GSN activity by phosphorylation. We also confirmed the regulatory role of CRE-1 in CCR and its nuclear localization under repressing condition in N. crassa. The expression of all glycogenic genes is misregulated in the cre-1(KO) strain, suggesting that CRE-1 also controls glycogen metabolism by regulating gene expression. The existence of a high number of the Aspergillus nidulans CreA motif (5'-SYGGRG-3') in the glycogenic gene promoters led us to analyze the binding of CRE-1 to some DNA motifs both in vitro by DNA gel shift and in vivo by ChIP-qPCR analysis. CRE-1 bound in vivo to all motifs analyzed demonstrating that it down-regulates glycogen metabolism by controlling gene expression and GSN phosphorylation.
A role in the regulation of transcription by light for RCO-1 and RCM-1, the Neurospora homologs of the yeast Tup1-Ssn6 repressor
Fungal Genet Biol 2010 Nov;47(11):939-52.PMID:20709620DOI:10.1016/j.fgb.2010.08.001.
The activation of gene transcription by light is transient since light-dependent mRNA accumulation ceases after long exposures to light. This phenomenon, photoadaptation, has been observed in plants and fungi, and allows the perception of changes in light intensities. In the fungus Neurosporacrassa photoadaptation involves the transient binding of the photoresponsive White Collar Complex (WCC) to the promoters of light-regulated genes. We show that RCO-1 and RCM-1, the Neurospora homologs of the components of the yeast Tup1-Ssn6 repressor complex, participate in photoadaptation. Mutation in either rco-1 or RCM-1 result in high and sustained accumulation of mRNAs for con-10 and other light-regulated genes after long exposures to light. The mutation of rco-1 increased the sensitivity to light for con-10 activation and delayed synthesis and/or degradation of con-10 and con-6 mRNAs without altering the amount or the light-dependent phosphorylation of the photoreceptor WC-1. RCO-1 and RCM-1 are located in the Neurospora nuclei were they regulate gene transcription. We show that RCO-1 and RCM-1 participate in the light-transduction pathway of Neurospora and has a role in photoadaptation by repressing gene transcription after long exposures to light.
The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice
Sci Signal 2017 Apr 18;10(475):eaai8583.PMID:28420758DOI:10.1126/scisignal.aai8583.
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens. RCM-1 blocked the nuclear localization and increased the proteasomal degradation of Forkhead box M1 (FOXM1), a transcription factor critical for the differentiation of goblet cells from airway progenitor cells. RCM-1 reduced airway resistance, increased lung compliance, and decreased proinflammatory cytokine production in mice exposed to the house dust mite and interleukin-13 (IL-13), which triggers goblet cell metaplasia. In cultured airway epithelial cells and in mice, RCM-1 reduced IL-13 and STAT6 (signal transducer and activator of transcription 6) signaling and prevented the expression of the STAT6 target genes Spdef and Foxa3, which are key transcriptional regulators of goblet cell differentiation. These results suggest that RCM-1 is an inhibitor of goblet cell metaplasia and IL-13 signaling, providing a new therapeutic candidate to treat patients with asthma and other chronic airway diseases.