Chiauranib
(Synonyms: CS2164) 目录号 : GC62145
Chiauranib (CS2164) selectively inhibits multiple kinase targets aurora B kinase (AURKB), colony-stimulating factor 1 receptor (CSF1R), and vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-Kit , thereby inhibiting the rapid proliferation of tumor cells, enhancing the antitumor immunity, and inhibiting tumor angiogenesis, to achieve the anti-tumor efficacy.
Cas No.:1256349-48-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chiauranib (CS2164) selectively inhibits multiple kinase targets aurora B kinase (AURKB), colony-stimulating factor 1 receptor (CSF1R), and vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-Kit , thereby inhibiting the rapid proliferation of tumor cells, enhancing the antitumor immunity, and inhibiting tumor angiogenesis, to achieve the anti-tumor efficacy.
[1] Zhou Y, et al. Cancer Sci. 2017 Mar;108(3):469-477.
| Cas No. | 1256349-48-0 | SDF | |
| 别名 | CS2164 | ||
| 分子式 | C27H21N3O3 | 分子量 | 435.47 |
| 溶解度 | DMSO : 62.5 mg/mL (143.52 mM; Need ultrasonic) | 储存条件 | 4°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 | 2.2964 mL | 11.4818 mL | 22.9637 mL |
| 5 mM | 0.4593 mL | 2.2964 mL | 4.5927 mL |
| 10 mM | 0.2296 mL | 1.1482 mL | 2.2964 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。
Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway
Pharmaceuticals (Basel) 2022 Dec 22;16(1):15.PMID:36678513DOI:10.3390/ph16010015.
Transformed follicular lymphoma (t-FL), for which there is no efficient treatment strategy, has a rapid progression, treatment resistance, and poor prognosis, which are the main reasons for FL treatment failure. In this study, we identified a promising therapeutic approach with Chiauranib, a novel orally developed multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. We first determined the cytotoxicity of Chiauranib in t-FL cell lines through CCK-8, EdU staining, flow cytometry, and transwell assays. We also determined the killing effect of Chiauranib in a xenograft model. More importantly, we identified the underlying mechanism of Chiauranib in t-FL tumorigenesis by immunofluorescence and Western blotting. Treatment with Chiauranib significantly inhibited cell growth and migration, promoted apoptosis, induced cell cycle arrest in G2/M phase, and resulted in significant killing in vivo. Mechanistically, Chiauranib suppresses the phosphorylation level of VEGFR2, which has an anti-t-FL effect by inhibiting the downstream MEK/ERK/STAT3 signaling cascade. In conclusion, Chiauranib may be a potential therapy to treat t-FL, since it inhibits tumor growth and migration and induces apoptosis by altering the VEGFR2/ERK/STAT3 signaling pathway.
Chiauranib selectively inhibits colorectal cancer with KRAS wild-type by modulation of ROS through activating the p53 signaling pathway
Am J Cancer Res 2020 Nov 1;10(11):3666-3685.PMID:33294260doi
Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiauranib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiauranib in the treatment of CRC remain to be elucidated. Our study shows that Chiauranib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiauranib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiauranib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiauranib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiauranib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiauranib. Our findings provide the rationale for further clinical evaluation of Chiauranib as a therapeutic agent in treating KRAS wild-type CRC.
Phase I dose-escalation study of Chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors
J Hematol Oncol 2019 Jan 14;12(1):9.PMID:30642372DOI:10.1186/s13045-018-0695-0.
Background: Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα, and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF-1R. This phase I dose-escalation study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor activity of Chiauranib in patients with refractory advanced solid tumor and lymphoma. Methods: Eighteen patients were treated with continuous dosing of Chiauranib from 10 to 65 mg once daily in a dose-escalation 3 + 3 design and evaluated in 28-day cycles. Pharmacokinetic profile of plasma Chiauranib was analyzed in both single and multiple dose studies. Results: Dose-limiting toxicity (DLT) as of grade 3 hypertension occurred in two patients at 65 mg/day, and one dose level below as MTD was 50 mg/day. The most common treatment-related adverse events included fatigue (61.1%), proteinuria (44.4%), hematuria (38.9%), hypothyroidism (38.9%), hypertriglyceridemia (33.3%), and hypertension (33.3%). A linear and dose-dependent pharmacokinetic profile of Chiauranib was characterized with rapid absorption and slow elimination feature in both single and multiple dose studies. The accumulative exposure of Chiauranib reached the steady state within 8 days and was approximately increased by twofold as those in the single dose study. No complete or partial response was observed, and 12 patients (66.7%) achieved stable disease (SD). Conclusions: Chiauranib demonstrated an acceptable safety and favorable pharmacokinetic profile with potential antitumor activity. Several phase Ib/II clinical studies are currently under further investigation. Trial registration: NCT, NCT02122809 . Registered 25 April 2014.
CS2164 suppresses acute myeloid leukemia cell growth via inhibiting VEGFR2 signaling in preclinical models
Eur J Pharmacol 2019 Jun 15;853:193-200.PMID:30928630DOI:10.1016/j.ejphar.2019.03.041.
Acute myeloid leukemia (AML) arises from neoplastic transformation of hematopoietic stem and progenitor cells, and resistance to conventional chemotherapy remains one of the greatest challenges in treating the disease. Extensive data have demonstrated that angiogenesis is associated with AML progression and chemotherapy resistance. Thus, targeting angiogenesis may be a promising approach for AML treatment. In this study, we investigated the effectiveness of CS2164 (named as Chiauranib), a novel receptor tyrosine kinase inhibitor, in AML cells. Our results illustrated that CS2164 significantly suppressed cell proliferation and abolished clonogenicity in AML cells in a dose- and time-dependent manner. Meanwhile, CS2164 markedly induced apoptosis of AML cell lines and primary AML cells from 42 adult patients. Furthermore, we found that CS2164 has a comprehensive activity against AML irrespective of disease status and genetic mutations. Also, CS2164 suppressed AML growth in xenograft models in vivo. Mechanistically, CS2164-induced cytotoxicity was closely associated with inhibition of VEGFR2 and its downstream signaling cascades, including Src/Fyn/p38 and Erk/MEK. In conclusion, our study indicates that CS2164 exerts anti-leukemia effect by inducing apoptosis through suppressing the VEGFR2 pathway, supporting a potential role for CS2164 in the treatment of AML.