Crotonoside
(Synonyms: 巴豆苷; Isoguanosine) 目录号 : GC38412
A guanosine analog with diverse biological activities
Cas No.:1818-71-9
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
Crotonoside is a guanosine analog originally isolated from C. tiglium that has diverse biological activities.1,2,3 It is cytotoxic to P338, L5178Y, Sp2/O, HL-60, and Raji cells in vitro (EC50s = 21, 370, 120, 70, and 400 μM, respectively).1 Crotonoside (48 mg/kg per day for 12 days) reduces tumor growth by 60% in S-180 sarcoma and Ehrlich carcinoma solid tumor mouse models. It has been used as an internal standard for the semi-quantitative analysis and comparison of RNA metabolites in MCF-7 breast cancer cells and MCF-10A mammary epithelial cells.4 Crotonoside decreases the force and rate of contraction in isolated guinea pig atria (EC50s = 2.8 and 17.8 μM, respectively) and reduces carotid blood pressure in anesthetized cats when administered intravenously at a dose of 0.5 μmol/kg.2,3
1.Kim, J.H., Lee, S.J., Han, Y.B., et al.Isolation of isoguanosine from Croton tiglium and its antitumor activityArch. Pharm. Res.17(2)115-118(1994) 2.Fuhrman, F.A., and Fuhrman, G.J.Effects of some naturally-occurring purine ribosides on purinergic receptors in cardiac and smooth muscleComp. Biochem. Physiol. C72(2)203-210(1982) 3.Ewing, P.L., Schlenk, F., and Emerson, G.A.Comparison of smooth muscle effects of crotonoside (isoguanosine) and adenosineJ. Pharmacol. Exp. Ther.97(3)379-383(1949) 4.Bullinger, D., Neubauer, H., Fehm, T., et al.Metabolic signature of breast cancer cell line MCF-7: Profiling of modified nucleosides via LC-IT MS couplingBMC Biochem.825(2007)
| Cas No. | 1818-71-9 | SDF | |
| 别名 | 巴豆苷; Isoguanosine | ||
| Canonical SMILES | OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC(C(N)=N3)=C2NC3=O)O1)O)O | ||
| 分子式 | C10H13N5O5 | 分子量 | 283.24 |
| 溶解度 | DMSO: 25 mg/mL (88.26 mM) | 储存条件 | Store at -20°C,protect from light |
| 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 | 3.5306 mL | 17.6529 mL | 35.3057 mL |
| 5 mM | 0.7061 mL | 3.5306 mL | 7.0611 mL |
| 10 mM | 0.3531 mL | 1.7653 mL | 3.5306 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。
Pharmacokinetics and tissue distribution of Crotonoside
Xenobiotica 2018 Jan;48(1):28-36.PMID:28100102DOI:10.1080/00498254.2016.1276311.
1. Crotonoside is a bioactive ingredient from Croton Herba with a strong antitumour activity. This study aimed to develop a highly sensitive and selective high-performance liquid chromatography (HPLC) method to quantify Crotonoside in biological samples for pharmacokinetics and distribution studies. 2. Protein precipitation by perchloric acid was used to separate Crotonoside from the biological samples, and the recovery rates for Crotonoside and the internal standard (luteoloside) were >80%. All calibration curves examining the Crotonoside levels in plasma and tissues were linear (all correlation coefficients > 0.99). 3. The response to Crotonoside appeared to be dose disproportional to the maximum plasma concentration and the area under the time-concentration curve in plasma over the range of 12.5-50.0 mg/kg, and Crotonoside was highly distributed in tissues after intravenous administration. The highest Crotonoside level was detected in the liver (28.79 ± 14.96 μg/g), whereas Crotonoside was undetected in the brain.
Crotonoside exhibits selective post-inhibition effect in AML cells via inhibition of FLT3 and HDAC3/6
Oncotarget 2017 Sep 8;8(61):103087-103099.PMID:29262547DOI:10.18632/oncotarget.20710.
Targeted therapies for the treatment of acute myeloid leukemia (AML), specifically the FLT3 inhibitors, have shown promising results. Nevertheless, it is very unlikely that inhibitors which target a single pathway will provide long-term disease control. Here, we report the characterization of Crotonoside, a natural product extracted from Chinese medicinal herb, Croton, for the treatment of AML via inhibition of FLT3 and HDAC3/6. In vitro, Crotonoside exhibited selective inhibition in AML cells. In vivo, Crotonoside treatment at 70 and 35 mg/kg/d produced significant AML tumor inhibition rates of 93.5% and 73.6%, respectively. Studies on the anti-AML mechanism of Crotonoside demonstrated a significant inhibition of FLT3 signaling, cell cycle arrest in G0/G1 phase, and apoptosis. In contrast to classic FLT3 inhibitor; sunitinib, Crotonoside was able to selectively suppress the expression of HDAC3 and HDAC6 without altering the expression of other HDAC isoforms. Inhibitors of HDAC3 and HDAC6; RGFP966 and HPOB, respectively, also exhibited selective inhibition in AML cells. Furthermore, we established novel signaling pathways including HDAC3/NF-κB-p65 and HDAC6/c-Myc besides FLT3/c-Myc which are aberrantly regulated in the progression of AML. In addition, Crotonoside alone or the combination of sunitinib/RFP966/HPOB exhibited a significant post-inhibition effect in AML cells by the inhibition of FLT3 and HDAC3/6. Inhibitors targeting the FLT3 and HDAC3/6 might provide a more effective treatment strategy for AML. Taken together, the present study suggests that Crotonoside could be a promising candidate for the treatment of AML, and deserves further investigations.
Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation
Plants (Basel) 2020 Nov 10;9(11):1535.PMID:33182776DOI:10.3390/plants9111535.
Crotonoside, a guanosine analog originally isolated from Croton tiglium, is reported to be a potent tyrosine kinase inhibitor with immunosuppressive effects on immune cells. Due to its potential immunotherapeutic effects, we aimed to evaluate the anti-arthritic activity of Crotonoside and explore its immunomodulatory properties in alleviating the severity of arthritic symptoms. To this end, we implemented the treatment of Crotonoside on collagen-induced arthritic (CIA) DBA/1 mice and investigated its underlying mechanisms towards pathogenic dendritic cells (DCs). Our results suggest that Crotonoside treatment remarkably improved clinical arthritic symptoms in this CIA mouse model as indicated by decreased pro-inflammatory cytokine production in the serum and suppressed expression of co-stimulatory molecules, CD40, CD80, and MHC class II, on CD11c+ DCs from the CIA mouse spleens. Additionally, Crotonoside treatment significantly reduced the infiltration of CD11c+ DCs into the synovial tissues. Our in vitro study further demonstrated that bone marrow-derived DCs (BMDCs) exhibited lower yield in numbers and expressed lower levels of CD40, CD80, and MHC-II when incubated with Crotonoside. Furthermore, LPS-stimulated mature DCs exhibited limited capability to prime antigen-specific CD4+ and T-cell proliferation, cytokine secretions, and co-stimulatory molecule expressions when treated with Crotonoside. Our pioneer study highlights the immunotherapeutic role of Crotonoside in the alleviation of the CIA via modulation of pathogenic DCs, thus creating possible applications of Crotonoside as an immunosuppressive agent that could be utilized and further explored in treating autoimmune disorders in the future.
Antiarrhythmic effect of Crotonoside by regulating sodium and calcium channels in rabbit ventricular myocytes
Life Sci 2020 Mar 1;244:117333.PMID:31962132DOI:10.1016/j.lfs.2020.117333.
Aims: Detect the antiarrhythmic effect of Crotonoside (Cro). Main methods: We used whole-cell patch-clamp techniques to detect the effects of Cro on action potentials (APs) and transmembrane ion currents in isolated rabbit left ventricular myocytes. We also verified the effect of Cro on ventricular arrhythmias caused by aconitine in vivo. Key findings: Cro reduced the maximum depolarization velocity (Vmax) of APs and shortened the action potential duration (APD) in a concentration-dependent manner, but it had no significant effect on the resting membrane potential (RMP) or action potential amplitude (APA). It also inhibited the peak sodium current (INa) and L-type calcium current (ICaL) in a concentration-dependent manner with half-maximal inhibitory concentrations (IC50) of 192 μmol/L and 159 μmol/L, respectively. However, Cro had no significant effects on the inward rectifier potassium current (IK1) or rapidly activating delayed rectifier potassium current (IKr). Sea anemone toxin II (ATX II) increased the late sodium current (INaL), but Cro abolished this effect. Moreover, Cro significantly abolished ATX II-induced early afterdepolarizations (EADs) and high extracellular Ca2+ concentration (3.6 mmol/L)-induced delayed afterdepolarizations (DADs). We also verified that Cro effectively delayed the onset time and reduced the incidence of ventricular arrhythmias caused by aconitine in vivo. Significance: These results revealed that Cro effectively inhibits INa, INaL, and ICaL in ventricular myocytes. Cro has antiarrhythmic potential and thus deserves further study.
The Identification of APOBEC3G as a Potential Prognostic Biomarker in Acute Myeloid Leukemia and a Possible Drug Target for Crotonoside
Molecules 2022 Sep 7;27(18):5804.PMID:36144542DOI:10.3390/molecules27185804.
The apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G) converts cytosine to uracil in DNA/RNA. Its role in resisting viral invasion has been well documented. However, its expression pattern and potential function in AML remain unclear. In this study, we carried out a bioinformatics analysis and revealed that the expression of APOBEC3G was significantly upregulated in AML, and high expression of APOBEC3G was significantly associated with short overall survival (OS). APOBEC3G expression was especially increased in non-M3AML, and correlated with the unfavorable cytogenetic risks. Additionally, Cox regression analyses indicated APOBEC3G is a hazard factor that cannot be ignored for OS of AML patients. In molecular docking simulations, the natural product Crotonoside was found to interact well with APOBEC3G. The expression of APOBEC3G is the highest in KG-1 cells, and the treatment with Crotonoside can reduce the expression of APOBEC3G. Crotonoside can inhibit the viability of different AML cells in vitro, arrest KG-1 and MV-4-11 cells in the S phase of the cell cycle and affect the expression of cycle-related proteins, and induce cell apoptosis. Therefore, APOBEC3G could be a potential drug target of Crotonoside, and Crotonoside can be considered as a lead compound for APOBEC3G inhibition in non-M3 AML.