| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| 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 belongs to the cyclohexenone class of compounds. More than a decade ago, scientists at the University of California, San Diego, synthesized a novel anticancer compound using the toxin from the poisonous pumpkin lantern mushroom. After demonstrating potential against one of the deadliest cancers, the compound received Fast Track designation from the U.S. Food and Drug Administration (FDA). MGI-114 (Irofulven) is currently being developed by MGI PHARMA, Inc., an emerging oncology pharmaceutical company located in Minneapolis. Phase III clinical trials of the drug have been conducted at multiple sites in the U.S. and Europe since early 2001. Irofulven is a semi-synthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens. Irofulven can alkylate DNA and protein macromolecules, forming adducts and arresting cells in the S phase of the cell cycle. The drug requires NADPH-dependent metabolism via enal/ketone oxidoreductases to exert its activity. Compared to other alkylating agents, Irofulven exhibits higher activity against epithelial-derived tumor cells in vitro and is more resistant to p53 deficiency and MDR1 inactivation. (NCI04)
Drug Indications It has been studied for the treatment of brain cancer, breast cancer, endometrial cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, pediatric diseases, prostate cancer, and sarcoma. Mechanism of Action MGI-114 (Irofulven), as an anti-tumor drug, has a unique mechanism of action in that it can be rapidly absorbed by tumor cells. After entering the cell, the compound binds to DNA and protein targets. This binding interferes with DNA replication and cell division in tumor cells, ultimately leading to tumor-specific apoptosis, or "cell suicide." In this process, when tumor cells sense that their own function is impaired, they often automatically shut themselves down. |
| 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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| Density |
1.28g/cm3
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| Boiling Point |
501ºC at 760 mmHg
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| Flash Point |
270.9ºC
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| Vapour Pressure |
3.9E-12mmHg at 25°C
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| Index of Refraction |
1.617
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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
|
| SMILES |
CC1=C(C2=C(C3(CC3)[C@@](C(=O)C2=C1)(C)O)C)CO
|
| 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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