Canfosfamide
Canfosfamide (TLK-286, TER286) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. Canfosfamide also inhibits the catalytic kinase activity of DNA-dependent protein kinase (DNA-PK). Canfosfamide produces an anticancer alkylating agent and a glutathione derivative after activation. Canfosfamide can be used to research malignancies.
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- CAS 番号: 158382-37-7
- 分子式: C26H40Cl4N5O10PS
- 分子量:787.47
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
製品説明
IC50 & Target
IC50: ~1 µM (DNA-PK)[3]
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| B16 | IC50 |
710 nM
Compound: TLK286; Telcyta
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Antiproliferative activity against mouse B16 cells after 72 hrs by MTT assay
Antiproliferative activity against mouse B16 cells after 72 hrs by MTT assay
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[PMID: 29420887] |
| MCF7 | IC50 |
870 nM
Compound: TLK286; Telcyta
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Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay
Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay
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[PMID: 29420887] |
体外実験
Canfosfamide (TLK-28) inhibit the catalytic kinase activity of purified DNA-dependent protein kinase (DNA-PK) with an IC50 value of ~1 µM, but causes minimal direct damage to DNA[2].
Canfosfamide (TER286) inhibits MCF-7, NIH-3T3 and M7609 in a dose-dependent manner[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MCF-7, NIH-3T3 and M7609
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Concentration:0-100 μM
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Incubation Time:Co-incubated for 2 h then removed and incubated for 5 days in MCF-7; co-incubated for 10 days in NIH-3T3; co-incubated for 48 h in M7609
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Result:Inhibited these cancer cell lines in a dose-dependent manner.
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (s.c. with tumors of M7609, MX-1 human breast tumor, lung tumor[3]
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Dosage:150 mg/kg for M7609 xenografts; 400 mg/kg or 200 mg/kg for other xenografts
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Administration:i.v., single dosage for M7609 xenograft; i.p., single dosage for other xenografts; i.p., daily for 5 days
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Result:The best response to TER286 was for the MX-1 human breast tumor treated with an aggressive regimen (daily for 5 days), under which nearly all of the tumors were either severely growth inhibited or substantially regressed.
化学情報
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CAS 番号 158382-37-7
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分子量 787.47
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分子式 C26H40Cl4N5O10PS
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SMILES
ClCCN(CCCl)P(N(CCCl)CCCl)(OCCS(C[C@H](NC(CC[C@H](N)C(O)=O)=O)C(N[C@H](C1=CC=CC=C1)C(O)=O)=O)(=O)=O)=O
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別名
TLK-286; TER286
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
プロトコル
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
純度とドキュメンテーション
参考文献
[1]. Dourado DF, et al. Mechanism of glutathione transferase P1-1-catalyzed activation of the prodrug canfosfamide (TLK286, TELCYTA). Biochemistry. 2013 Nov 12;52(45):8069-78. [Content Brief]
[2]. Tew KD. TLK-286: a novel glutathione S-transferase-activated prodrug. Expert Opin Investig Drugs. 2005 Aug;14(8):1047-54. [Content Brief]
[3]. Morgan AS, et al. Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase. Cancer Res. 1998 Jun 15;58(12):2568-75. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)