Chetomin (also called NSC289491, BRN0077366), an antibiotic metabolite of chaetomium cochliodes and a natural product isolated from Chaetomium species which has anticancer, antibacterial and antifungal properties, is an inhibitor of HIF-1 which weakens transcription of HIF-1, and disrupts the binding of HIF-1α and HIF-2α to p300 at low nanomolar concentrations. Chetomin may find application as a chemotherapeutic agent for cancer treatment. Chetomin specifically inhibits HIF-1 activities by interfering with HIF-1's interaction with p300, a transcriptional coactivator. In vitro, chetomin-induced HIF-1 inhibition significantly lowers hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells. Additionally, chemomin causes XIAP to break down and increases TRAIL sensitivity in urogenital cancer cells.

Physicochemical Properties

Molecular Formula	C31H30N6O6S4
Molecular Weight	710.87
Exact Mass	712.126
Elemental Analysis	C, 52.38; H, 4.25; N, 11.82; O, 13.50; S, 18.04
CAS #	1403-36-7
Related CAS #	1403-36-7
PubChem CID	10417379
Appearance	White to light yellow solid powder
Density	1.8±0.1 g/cm3
Melting Point	710.9ºC
Index of Refraction	1.869
LogP	3.85
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	5
Heavy Atom Count	47
Complexity	1460
Defined Atom Stereocenter Count	6
SMILES	CN1C(=O)[C@@]2(CO)N(C)C(=O)[C@]1(CC3=CN(C4=CC=CC=C34)[C@]56C[C@]78C(=O)N(C)[C@](CO)(C(=O)N7[C@H]5NC9=CC=CC=C96)SS8)SS2
InChi Key	ZRZWBWPDBOVIGQ-YWZWRZHGSA-N
InChi Code	InChI=1S/C31H30N6O6S4/c1-33-25(42)30(15-38)34(2)23(40)28(33,44-46-30)12-17-13-36(21-11-7-4-8-18(17)21)27-14-29-24(41)35(3)31(16-39,47-45-29)26(43)37(29)22(27)32-20-10-6-5-9-19(20)27/h4-11,13,22,32,38-39H,12,14-16H2,1-3H3/t22-,27+,28+,29+,30+,31+/m1/s1
Chemical Name	(1S,3S,11R,14S)-14-(hydroxymethyl)-3-[3-[[(1S,4S)-4-(hydroxymethyl)-5,7-dimethyl-6,8-dioxo-2,3-dithia-5,7-diazabicyclo[2.2.2]octan-1-yl]methyl]indol-1-yl]-18-methyl-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-triene-13,17-dione
Synonyms	NSC289491; BRN0077366; Chetomin; CTM; NSC-289491; NSC 289491
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	HSP90
ln Vitro	Hypoxia-inducible factors 1 (HIF-1) is a transcription factor that reacts to oxygen changes in the cellular environment. Chetomin specifically inhibits HIF-1 activities by interfering with HIF-1's interaction with p300, a transcriptional coactivator. In vitro, chetomin-induced HIF-1 inhibition significantly lowers hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells. Chetomin reduces malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18) and U343MG (DMF10: 1.78 and 1.48) radioresistance caused by hypoxia. Hypoxia-inducible factor-1α's differentiation-inhibitory effect is eliminated when HIF-1 is targeted with chetomin.
ln Vivo	In an in vivo xenograft model, the coadministration of chetomin and forskolin significantly suppresses the growth of malignant gliomas. Che-M (chetomin loaded micelles) significantly suppresses zebrafish tumor growth, tumor-induced angiogenesis, and embryonic angiogenesis. Che-M inhibits the growth of tumors in mice and increases the survival time of the subcutaneous CT26 tumor model.
Cell Assay	Chetomin is added to fully supplemented medium in RT-PCR and clonogenic survival experiments at a concentration of 150 nM four hours prior to treatment with hypoxia. After that, without altering the medium, HT 1080 cells are moved to either the well-humidified incubator (12 hours) or the hypoxic workstation (0.1% O2). Therefore, HT1080 cells are treated with chetomin (150 nM) for 16 hours before receiving radiation therapy.
Animal Protocol	Chetomin was loaded in micelles; 1 mg/mL(for zebrafish); 2 mg/kg(for mouse); s.c. Transgenic fish Tg(flk1:EGFP); Mouse model(BALB/c mice)
References	[1]. Chetomin, a Hsp90/HIF1α pathway inhibitor, effectively targets lung cancer stem cells and non-stem cells. Cancer Biol Ther. 2020;21(8):698-708.
Additional Infomation	Chetomin has been reported in Chaetomium cochliodes, Chaetomium elatum, and other organisms with data available.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~140.7 mM) Water: <1 mg/mL Ethanol: ~10 mg/mL (~14.0 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4067 mL	7.0336 mL	14.0673 mL
	5 mM	0.2813 mL	1.4067 mL	2.8135 mL
	10 mM	0.1407 mL	0.7034 mL	1.4067 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.