| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
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| ln Vitro |
(-)-Irofulven (2.8 μM; 1 hour) triggers p53-dependent cell cycle arrest [1]. Induction of CHK2 activation by (-)-Irofulven (0.8 μM, 0.9 μM and 2.8 μM; 1 hour) corresponds with p53 status in cells [1]. (-)-Irofulven inhibits DNA replication and generates chromosomal abnormalities (breaks and radials) [1].
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|---|---|
| ln Vivo |
(-)-Irofulven (7 mg/kg; intraperitoneal injection; days 1-5 and 8-12) significantly enhances the median survival rate of mice carrying tumor cells [2].
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| Cell Assay |
Cell cycle analysis [1]
Cell Types: A2780, CAOV3 and HCT116 Cell Tested Concentrations: 2.8 μM Incubation Duration: 1 hour Experimental Results: p53 wild-type cells mainly arrested in G1/S phase, while p53 mutant or p53 deleted cells arrested in G1/ S period. S and G2/M stages. Western Blot Analysis[1] Cell Types: A2780, CAOV3 and HCT116 Cell Tested Concentrations: 0.8 μM, 0.9 μM and 2.8 μM Incubation Duration: 1 hour Experimental Results: Induction of Thr 68 phosphorylation of intracellular CHK2 kinase. |
| Animal Protocol |
Animal/Disease Models: Male and female athymic balb/c (Bagg ALBino) mouse (nu/nu genotype, 6 weeks of age or older) injected with human glioblastoma multiforme [2].
Doses: 7 mg/kg Route of Administration: intraperitoneal (ip) injection; Days 1-5 and 8-12 Experimental Results: Active against all tumor lines. |
| References |
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| Additional Infomation |
Irofulven is a member of cyclohexenones.
A novel anti-cancer compound synthesized by scientists at the University of California, San Diego more than a decade ago from toxins of the poisonous jack-o-lantern mushroom, has been granted “fast track” status by the U.S. Food and Drug Administration (FDA) after demonstrating promise against one of the most deadly cancers. MGI-114 (Irofulven) is currently being developed by MGI PHARMA, Inc., an emerging oncology-focused pharmaceutical company based in Minneapolis. Phase III clinical trials involving the drug have been underway since early 2001 at sites in the U.S. and Europe. Irofulven is a semisynthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens. Irofulven alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle. This agent requires NADPH-dependent metabolism by alkenal/one oxidoreductase for activity. Irofulven is more active in vitro against tumor cells of epithelial origin and is more resistant to deactivation by p53 loss and MDR1 than other alkylating agents. (NCI04) Drug Indication Investigated for use/treatment in brain cancer, breast cancer, endometrial cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, pediatric indications, prostate cancer, and sarcoma. Mechanism of Action MGI-114(Irofulven) has unique mechanism of action as an anti-tumor agent is due to its ability to be rapidly absorbed by tumor cells. Once inside the cells, the compound binds to DNA and protein targets. This binding interferes with DNA replication and cell division of tumor cells, leading to tumor-specific apoptotic cell death, or “cell suicide.” During this process, tumor cells tend to automatically shut themselves down when they sense their function is compromised. |
| Molecular Formula |
C15H18O3
|
|---|---|
| Molecular Weight |
246.30162
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| Exact Mass |
246.125
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| Elemental Analysis |
C, 73.15; H, 7.37; O, 19.49
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| CAS # |
158440-71-2
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| PubChem CID |
148189
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| Appearance |
Yellow to orange solid powder
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| LogP |
-0.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
558
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C2=C(C3(CC3)[C@@](C(=O)C2=C1)(C)O)C)CO
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| InChi Key |
NICJCIQSJJKZAH-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C15H18O3/c1-8-6-10-12(11(8)7-16)9(2)15(4-5-15)14(3,18)13(10)17/h6,16,18H,4-5,7H2,1-3H3/t14-/m0/s1
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| Chemical Name |
(5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one
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| Synonyms |
MGI 114; HMAF; Irofulven
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~203.00 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0601 mL | 20.3004 mL | 40.6009 mL | |
| 5 mM | 0.8120 mL | 4.0601 mL | 8.1202 mL | |
| 10 mM | 0.4060 mL | 2.0300 mL | 4.0601 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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