Chloroquinoxaline sulfonamide
(Synonyms: 4-氨基-N-(5-氯-2-喹喔啉)苯磺酰胺,Chloroquinoxaline; NSC-339004) 目录号 : GC60107
Chloroquinoxaline sulfonamide (Chloroquinoxaline) 是 sulfaquinoxaline 的结构类似物，是拓扑异构酶 II alpha/beta (topoisomerase II alpha/beta) 毒物。Chloroquinoxaline sulfonamide 用于控制家禽，兔，绵羊和牛的球虫病。 具有抗肿瘤活性。
Cas No.:97919-22-7
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
Chloroquinoxaline sulfonamide (Chloroquinoxaline), a structural analogue of sulfaquinoxaline, is a topoisomerase II alpha/beta poison. Chloroquinoxaline sulfonamide is used to control coccidiosis in poultry, rabbit, sheep, and cattle[1]. Antitumor activity[2].
The Chloroquinoxaline sulfonamide IC50 for CV-1cells, obtained using an MTT cytotoxicity assay, was 1.8 mM. Chloroquinoxaline sulfonamide causes dose-dependent protein-DNA cross-links to CV-1 monkey kidney cell chromosomal DNA when drug treatment was terminated by lysis with GuHCl. Chloroquinoxaline sulfonamide-induced protein-DNA cross-links in CV-1 cells. Chloroquinoxaline sulfonamide-induced topoisomerase II-DNA cross-links[1].Chloroquinoxaline sulfonamide (Chloroquinoxaline), a chlorinated derivative of sulfaquinoxaline, inhibits proliferation of murine B16 melanoma cells, but only when relatively high drug concentrations (1 mM) are used[2]. Cell Proliferation Assay[2] Cell Line: B16 murine melanoma cells
[1]. Gao H, et al. Chloroquinoxaline sulfonamide (NSC 339004) is a topoisomerase IIalpha/beta poison. Cancer Res. 2000 Nov 1;60(21):5937-40. [2]. Branda RF, et al. Cellular pharmacology of chloroquinoxaline sulfonamide and a related compound in murine B16 melanoma cells. Biochem Pharmacol. 1988 Dec 1;37(23):4557-64.
| Cas No. | 97919-22-7 | SDF | |
| 别名 | 4-氨基-N-(5-氯-2-喹喔啉)苯磺酰胺,Chloroquinoxaline; NSC-339004 | ||
| Canonical SMILES | ClC1=CC=CC2=NC(NS(=O)(C3=CC=C(N)C=C3)=O)=CN=C12 | ||
| 分子式 | C14H11ClN4O2S | 分子量 | 334.78 |
| 溶解度 | DMSO: 125 mg/mL (373.38 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 | 2.987 mL | 14.9352 mL | 29.8704 mL |
| 5 mM | 0.5974 mL | 2.987 mL | 5.9741 mL |
| 10 mM | 0.2987 mL | 1.4935 mL | 2.987 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。
Chloroquinoxaline sulfonamide: a sulfanilamide antitumor agent entering clinical trials
Invest New Drugs 1993 Feb;11(1):1-9.PMID:8349430DOI:10.1007/BF00873904.
Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame. The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45-132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans. Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2.
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15
Science 2017 Apr 28;356(6336):eaal3755.PMID:28302793DOI:10.1126/science.aal3755.
Indisulam is an aryl sulfonamide drug with selective anticancer activity. Its mechanism of action and the basis for its selectivity have so far been unknown. Here we show that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. Mutations in RBM39 that prevent its recruitment to CUL4-DCAF15 increase RBM39 stability and confer resistance to indisulam's cytotoxicity. RBM39 associates with precursor messenger RNA (pre-mRNA) splicing factors, and inactivation of RBM39 by indisulam causes aberrant pre-mRNA splicing. Many cancer cell lines derived from hematopoietic and lymphoid lineages are sensitive to indisulam, and their sensitivity correlates with DCAF15 expression levels. Two other clinically tested sulfonamides, tasisulam and Chloroquinoxaline sulfonamide, share the same mechanism of action as indisulam. We propose that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides).
Chloroquinoxaline sulfonamide (NSC 339004) is a topoisomerase IIalpha/beta poison
Cancer Res 2000 Nov 1;60(21):5937-40.PMID:11085507doi
Chloroquinoxaline sulfonamide (chlorosulfaquinoxaline, CQS, NSC 339004) is active against murine and human solid tumors. On the basis of its structural similarity to the topoisomerase IIbeta-specific drug XK469, CQS was tested and found to be both a topoisomerase-IIalpha and a topoisomerase-IIbeta poison. Topoisomerase II poisoning by CQS is essentially undetectable in assays using the common protein denaturant SDS, but easily detectable with strong chaotropic protein denaturants. The finding that detection of topoisomerase poisoning can be so dependent on the protein denaturant used in the assay has implications for drug discovery efforts and for our understanding of topoisomerase poisons.
Immunosuppressive properties of Chloroquinoxaline sulfonamide
Biochem Pharmacol 1989 Oct 15;38(20):3521-6.PMID:2818644DOI:10.1016/0006-2952(89)90123-8.
Chloroquinoxaline sulfonamide (CQS), a sulfanilamide derivative with antitumor activity, was found to be toxic to lymphoid tissue during preclinical studies. The mechanism of this toxicity appears to involve profound inhibition of lymphocyte activation. Incubation of human peripheral blood mononuclear cells (PBMNCs) with CQS decreased cellular incorporation of thymidine and deoxyuridine in a dose-dependent manner. Analysis of cell cycle distribution by flow cytometry indicated that CQS blocked movement out of the G0/G1 phase. Drug-treated cells were smaller and expressed fewer receptors for interleukin-2 (IL-2) and transferrin than untreated mitogen-stimulated lymphocytes. These observations support the notion that CQS has cell cycle specificity in regulating lymphocyte proliferation. As little as 10 microM CQS markedly inhibited both human lymphocyte and murine CTLL cell replication in response to IL-2 containing growth factors. However, CQS did not block secretion of IL-2 into culture supernatant fractions by human PBMNCs. Finally, CQS inhibited in vitro production of immunoglobulins G and M by mitogen-stimulated lymphocytes, primarily by causing cytotoxicity. In all of these drug effects, CQS was approximately one to two logs more potent than the parent compound, sulfaquinoxaline (SQ). These studies indicate that CQS inhibits essential basic processes in human lymphocytes. This agent may find use as an immunosuppressive drug.
A phase II study of Chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC)
Invest New Drugs 2006 Jul;24(4):343-6.PMID:16446986DOI:10.1007/s10637-005-4827-3.
Purpose: Phase II multicenter study investigated the efficacy and toxicity of the novel halogenated derivative of sulfaquixonaline Chloroquinoxaline sulfonamide (CQS) in metastatic colorectal cancer. Experimental design: Eligible patients with metastatic or recurrent colorectal cancer received CQS at a dose schedule of 2000 mg/m2 over an hour weekly for 4 weeks every 42 days. Treatment was continued until unexpected toxicity or disease progression. Results: A total of seventeen patients were enrolled on this study. 94% of all patients enrolled had prior treatment. Sixteen patients were evaluable for response with fifteen patients showing evidence of disease progression and one patient with prolonged stable disease. One patient had non-evaluable disease. Following this interim analysis, the drug was considered ineffective and the study was terminated early. The most frequent adverse event was anemia. No patients discontinued the treatment because of toxicity. Conclusion: CQS, when given at a dose of 2000 mg/m2 weekly for 4 weeks every 42 days to patients with metastatic colorectal cancer, does not result in significant tumor regression.