Chetomin (Synonyms: NSC 289491) |
رقم الكتالوجGC17405
One-Click Copy Product Info
|
Chetomin is a natural alkaloid derived from Chaetomium species, known for its significant anticancer and anti-inflammatory properties.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1403-36-7
Sample solution is provided at 25 µL, 10mM.
Chetomin is a natural alkaloid derived from Chaetomium species, known for its significant anticancer and anti-inflammatory properties[1]. Chetomin functions by inhibiting hypoxia-inducible factor-1 (HIF-1) and disrupting the interaction between HIF-1α and p300, thereby suppressing hypoxia-related gene transcription[2]. Chetomin serves as an important tool compound for studying hypoxia signaling pathways[3]. Additionally, Chetomin has demonstrated efficacy in tumor models by inhibiting tumor growth and angiogenesis[4].
In vitro, Chetomin (1–100nM) treatment of non-small cell lung cancer (NSCLC) cell lines H1299 and H460 in tumor spheroid cultures for 2 weeks significantly inhibited spheroid formation and the expression of stemness markers (Sox2, Nanog, Oct4), reduced the proportion of cancer stem cells with high aldehyde dehydrogenase activity (ALDH⁺), and induced apoptosis via activation of caspase-3 and PARP cleavage. In non-stem NSCLC cells, Chetomin (1–10μM) treatment for 24 hours significantly inhibited cell proliferation and colony formation, induced cell cycle arrest in the sub-G0/G1 phase, and exerted cytotoxic effects through a caspase-3-dependent apoptotic mechanism[5]. Chetomin (1.56–25nM) treatment of human multiple myeloma cell lines (HMCL) and primary myeloma cells for 4 days significantly inhibited cell growth and induced cytotoxicity, particularly in myeloma cells with high EP300/HIF-1α expression, while downregulating the expression of HIF-1α target genes (VEGF, IL-8, and CCL3)[6].
In vivo, Chetomin (0.5mg/kg) was administered intraperitoneally to C57BL/6J mice exposed to LiCoO₂ (LCO) particles via oropharyngeal aspiration, with treatment starting one day before exposure and continuing for two days post-exposure. Chetomin significantly attenuated LCO-induced early lung inflammation, including neutrophil infiltration and elevated levels of IL-1β and IL-6, and effectively inhibited HIF-1α activation in lung tissue[7]. Chetomin (1 and 5mg/kg) was administered via intraperitoneal injection to mice bearing U251-MG glioblastoma multiforme xenografts. Treatment was initiated when the tumor volume reached approximately 200mm³ and continued for 25 or 42 days. Chetomin significantly inhibited tumor growth in a dose-dependent manner and reduced the expression of p-FAK, p-AKT, and PCNA in tumor tissues[8].
References:
[1] Staab A, Loeffler J, Said HM, et al. Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma cells. BMC Cancer. 2007 Nov 13;7:213.
[2] Bravo-Reyna C, Zentella A, Ventura-Gallegos J, et al. Experimental Lung Transplantation Related With HIF-1, VEGF, ROS. Assessment of HIF-1alpha, VEGF, and Reactive Oxygen Species After Competitive Blockade of Chetomin for Lung Transplantation in Rats. Physiol Res. 2024 Nov 19;73(5):809-817.
[3] Dewangan J, Srivastava S, Mishra S, et al. Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction. Biochem Biophys Res Commun. 2018 Jan 8;495(2):1915-1921.
[4] Yano K, Horinaka M, Yoshida T, et al. Chetomin induces degradation of XIAP and enhances TRAIL sensitivity in urogenital cancer cells. Int J Oncol. 2011 Feb;38(2):365-74.
[5] Min S, Wang X, Du Q, et al. Chetomin, a Hsp90/HIF1α pathway inhibitor, effectively targets lung cancer stem cells and non-stem cells. Cancer Biol Ther. 2020 Aug 2;21(8):698-708.
[6] Viziteu E, Grandmougin C, Goldschmidt H, et al. Chetomin, targeting HIF-1α/p300 complex, exhibits antitumour activity in multiple myeloma. Br J Cancer. 2016 Mar 1;114(5):519-23.
[7] Sironval V, Palmai-Pallag M, Vanbever R, et al. HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles. Part Fibre Toxicol. 2019 Sep 18;16(1):35.
[8] Lee J, Kim E, Chong K, et al. Atypical induction of HIF-1α expression by pericellular Notch1 signaling suffices for the malignancy of glioblastoma multiforme cells. Cell Mol Life Sci. 2022 Oct 2;79(10):537.
| Cell experiment [1]: | |
Cell lines | Human non-small cell lung cancer (NSCLC) cell lines H1299 and H460, including paclitaxel-resistant sublines H460/R and H226B/R. |
Preparation Method | Cells were cultured under hypoxic conditions (1% O₂) for 24 hours to activate HIF-1α signaling. Chetomin was added at concentrations ranging from nanomolar (for sphere-forming assays) to micromolar (for monolayer proliferation assays) during hypoxia exposure. Cells were divided into control (vehicle-treated), hypoxia-only, and Chetomin-treated hypoxia groups. |
Reaction Conditions | 1–100nM for sphere formation; 1–10μM for proliferation assays; 24 hours (monolayer) or 2 weeks (sphere culture). |
Applications | Chetomin significantly inhibited sphere formation and stemness marker expression (Sox2, Nanog, Oct4) in NSCLC cancer stem cells, and reduced proliferation in both parental and chemoresistant NSCLC non-stem cells. Chetomin induced apoptosis via caspase-3 activation and PARP cleavage, while showing minimal toxicity to non-cancerous cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6JRj mice |
Preparation Method | Mice were exposed to LiCoO₂ (LCO) particles (0.5 or 2mg) via oro-pharyngeal aspiration. Chetomin (0.5mg/kg/day) was administered intraperitoneally starting one day before particle exposure and continued for two days. Mice were euthanized three days post-exposure for analysis |
Dosage form | 0.5mg/kg/day; i.p. |
Applications | Chetomin significantly reduced LCO-induced lung inflammation by decreasing alveolar inflammatory cell infiltration and neutrophil recruitment, downregulating pro-inflammatory cytokines IL-1β and IL-6 in bronchoalveolar lavage fluid (BALF), and attenuating HIF-1α stabilization in lung tissue. These effects were specific to LCO-induced inflammation and not observed in silica-exposed controls. |
References: | |
| Cas No. | 1403-36-7 | SDF | |
| المرادفات | NSC 289491 | ||
| Chemical Name | (3S,5aR,10bS,11aS)-2,3,5a,6,10b,11-hexahydro-3-(hydroxymethyl)-10b-(3-[(1S,4S)-3-[[4-(hydroxymethyl)-5,7-dimethyl-6,8-dioxo-2,3-dithia-5,7-diazabicyclo[2.2.2]oct-1-yl)methyl]-1H-indol-1-yl]-2-methyl-3,11a-epidithio-11aH-pyrazino[1,2:1,5]pyrrolo[2,3-b]indo | ||
| Canonical SMILES | O=C([C@@](N1C)(SS2)CC3=CN([C@@]([C@]4([H])N5)(C[C@@]6(SS7)N4C([C@@]7(CO)N(C)C6=O)=O)C8=C5C=CC=C8)C9=C3C=CC=C9)N(C)[C@]2(CO)C1=O | ||
| Formula | C31H30N6O6S4 | M.Wt | 710.87 |
| الذوبان | 5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4067 mL | 7.0336 mL | 14.0673 mL |
| 5 mM | 281.3 μL | 1.4067 mL | 2.8135 mL |
| 10 mM | 140.7 μL | 703.4 μL | 1.4067 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >95.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)