FUMITREMORGIN C
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| Category | Enzyme inhibitors |
| Catalog number | BBF-04546 |
| CAS | 118974-02-0 |
| Molecular Weight | 379.45 |
| Molecular Formula | C22H25N3O3 |
| Purity | ≥95% |
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Description
Fumitremorgin C, isolated from Aspergillus fumigatus, is a potent and specific inhibitor of the breast cancer resistance protein (BCRP/ABCG2) multidrug transporter. It reverses multidrug resistance mediated by BCRP and increases cytotoxicity of several anticancer agents in vitro.
Specification
| Synonyms | tryproquivaline D (2'S-(2'alpha,9'alpha(4R*(S*)),9'abeta))-isomer; tryproquivaline L (9'R-(9'alpha(R*),9'abeta))-isomer; tryproquivaline M (2'S-(2'alpha,9'alpha(4R*(S*)),9'abeta))-isomer; tryproquivaline N (2'S-(2'alpha,9'alpha(R*),9'abeta))-isomer; tryptoquivaline; (5aS,12S,14aS)-1,2,3,5a,6,11,12,14a-Octahydro-9-methoxy-12-(2-methyl-1-propen-1-yl)-5H,14H-pyrrolo[1'',2'':4',5']pyrazino[1',2':1,6]pyrido[3,4-b]indole-5,14-dione |
| Storage | Store at -20°C |
| IUPAC Name | (1S,12S,15S)-7-methoxy-12-(2-methylprop-1-enyl)-10,13,19-triazapentacyclo[11.7.0.03,11.04,9.015,19]icosa-3(11),4(9),5,7-tetraene-14,20-dione |
| Canonical SMILES | CC(=CC1C2=C(CC3N1C(=O)C4CCCN4C3=O)C5=C(N2)C=C(C=C5)OC)C |
| InChI | InChI=1S/C22H25N3O3/c1-12(2)9-18-20-15(14-7-6-13(28-3)10-16(14)23-20)11-19-21(26)24-8-4-5-17(24)22(27)25(18)19/h6-7,9-10,17-19,23H,4-5,8,11H2,1-3H3/t17-,18-,19-/m0/s1 |
| InChI Key | DBEYVIGIPJSTOR-FHWLQOOXSA-N |
| Source | Fumitremorgin C is a mycotoxin that has been found in the fungus Aspergillus fumigatus. |
Properties
| Appearance | White to Light Yellow Solid |
| Boiling Point | 642.9±55.0°C at 760 Torr |
| Melting Point | 259.5-260.5°C |
| Density | 1.34±0.1 g/cm3 |
| Solubility | Slightly soluble in DMSO, Chloroform |
Toxicity
| Carcinogenicity | No indication of carcinogenicity to humans (not listed by IARC). |
| Mechanism Of Toxicity | Fumitremorgin C inhibits ATP-binding cassette transporter (ACBG2), also known as breast cancer resistance protein. ACBG2 is known to confer multidrug resistance and also affects the bioavailability of different drugs. Thus fumitremorgin C is often used to sensitize cancer patients to chemotherapeutic drugs. Tremorgenic mycotoxins exert their toxic effects by interfering with neurotransmitter release, possibly by causing degeneration of nerve terminals. They are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse. |
Reference Reading
1. Fumitremorgin C Attenuates Osteoclast Formation and Function via Suppressing RANKL-Induced Signaling Pathways
Yu Yuan, Kai Chen, Xi Chen, Chao Wang, Heng Qiu, Zhen Cao, Dezhi Song, Youqiang Sun, Jianmin Guo, Jennifer Tickner, Jiake Xu, Jun Zou Front Pharmacol. 2020 Mar 10;11:238. doi: 10.3389/fphar.2020.00238. eCollection 2020.
Excessive bone resorption conducted by osteoclasts is considered as the main cause of osteoclast-related bone diseases such as osteoporosis. Therefore, the suppression of excessive osteoclast formation and function is one of the strategies to treat osteoclast-related bone diseases. Fumitremorgin C (Fum) is a mycotoxin extracted from Aspergillus fumigatus. It has been shown to have extensive pharmacological properties, but its role in the treatment of osteoclast-related bone diseases remains unclear. In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together, the present study showed that Fum could attenuate the formation and function of osteoclast via suppressing RANKL-induced signaling pathways, suggesting that Fum might be a potential novel drug in the treatment of osteoclast-related bone diseases.
2. Chevalone C analogues and globoscinic acid derivatives from the fungus Neosartorya spinosa KKU-1NK1
Oue-Artorn Rajachan, Kwanjai Kanokmedhakul, Wareerat Sanmanoch, Sophon Boonlue, Supa Hannongbua, Patchreenart Saparpakorn, Somdej Kanokmedhakul Phytochemistry. 2016 Dec;132:68-75. doi: 10.1016/j.phytochem.2016.09.008. Epub 2016 Sep 25.
Four meroterpenoids, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11-dihydroxychevalone C, and 11-hydroxychevalone C and two ester epimers, 2S,4S-spinosate and 2S,4R-spinosate, together with seven known compounds, chevalones B, C, and E, tryptoquivaline, nortryptoquivaline, tryptoquivaline L, and quinadoline A were isolated from the fungus Neosartorya spinosa. Their structures were established based on spectroscopic data analyses. The theoretical ECD spectra of epimers, 2S,4S-spinosate and 2S,4R-spinosate were calculated to support the experimental results of their CD spectra. 1-hydroxychevalone C exhibited antimycobacterial activity against Mycobacterium tuberculosis with a MIC value of 26.4 μM. 1-Acetoxychevalone C and tryptoquivaline showed antimalarial activity against Plasmodium falciparum with IC50 values of 6.67 and 2.65 μM, respectively. In addition, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11-dihydroxychevalone C and quinadoline A showed cytotoxicity against KB and NCI-H187 cancer cell lines with IC50 values in the range of 32.7-103.3 μM.
3. Fumitremorgin C alleviates advanced glycation end products (AGE)-induced chondrocyte inflammation and collagen II and aggrecan degradation through sirtuin-1 (SIRT1)/nuclear factor (NF)-κB/ mitogen-activated protein kinase (MAPK)
Yeli Zhou, Jing Li, Chenglong Wang, Zheer Pan Bioengineered. 2022 Feb;13(2):3867-3876. doi: 10.1080/21655979.2021.2024387.
Fumitremorgin C is a potent and selective inhibitor of the breast cancer resistance protein. This study aimed to explore the role of fumitremorgin C in osteoarthritis (OA) and disclose the underlying mechanism. The cell viability of AGE-treated SW1353 cells in the presence of fumitremorgin C was detected by Cell Counting Kit-8 (CCK-8) assay. The inflammation and extracellular matrix (ECM) deposition of AGE-induced SW1353 cells was respectively measured by enzyme linked immunosorbent assay (ELISA), immunofluorescence, and Western blot. The expression of SIRT1 and NF-KB/MAPK signal was examined by Western blot. After that, SIRT1 inhibitor EX527 was added to observe the mechanism of action of fumitremorgin C. Fumitremorgin C restored the cell viability of SW1353 cells injured by AGE. Furthermore, it alleviated inflammation and ECM degradation in AGE-induced SW1353 cell. The SIRT1 expression decreased by AGE was recovered upon fumitremorgin C to SW1353 cells. The ratio of phosphorylated p65 (p-p65) and p65, phosphorylated JNK (p-JNK) and JNK, and phosphorylated 38 (p-38) and 38 were increased by AGE treatment, which was recovered by fumitremorgin C addition. SIRT1 inhibitor EX527 reverts the repressive effects of fumitremorgin C on inflammation and ECM degradation in AGE-induced SW1353 cell. In conclusion, fumitremorgin C alleviates AGE-induced inflammation and the degradation of collagen II and aggrecan through SIRT1/NF-κB/MAPK, which reveals the underlying mechanism by which fumitremorgin C alleviates OA.
Spectrum
Predicted LC-MS/MS Spectrum - 10V, Positive
Experimental Conditions
Ionization Mode: Positive
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
