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Purity: ≥98%
Erastin is a cell-permeable small molecule and potent ferroptosis activator by acting on mitochondrial VDAC with potential antineoplastic activity. It exhibits selectivity for tumor cells bearing oncogenic RAS and shows high in vivo antitumor efficacy in mice with HT-29 xenograft. Erastin is an antitumor agent selective for tumor cells bearing oncogenic RAS (i.e. HRAS, KRAS). Ferroptosis is a unique iron-dependent form of nonapoptotic cell death. It is triggered by oncogenic RAS-selective lethal small molecule erastin. Acitvation of ferroptosis lead to nonapoptotic destruction of cancer cells.
| Targets |
VDAC2; VDAC3
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| ln Vitro |
Ferroptosis in ectopic endometrial stromal cells (EESC) is triggered by erematin (10 μM; 24 hours), and at 9 hours, total ROS levels rise [1]. In EESC cells, erythrin can reduce the length of mitochondria and raise their membrane density [1]. Iron-related proteins, including FPN (iron export protein), have lower levels of mRNA expression in EESCs when treated with erythrin (10 μM) for nine hours. On the other hand, overexpression of FPN can considerably prevent Erastin-induced ferroptosis of EESCs [1]. In HT-29 colorectal cancer cells, erematin (10 μM; 24 hours) causes the opening of the mitochondrial permeability transition pore (mPTP) [2]. The proliferation of HT-29 colorectal cancer cells is greatly inhibited by eratin (30 μM; 72 hours) [2]. The genes that control iron metabolism or mitochondrial fatty acid metabolism are involved in the biological mechanism by which erythropoidin triggers ferroptosis. comprises tetrapeptide repeat domain 35, citrate synthase, ATP synthase F0 complex subunit C3, ribosomal protein L8, iron response element binding protein 2 (IREB2), and acyl-CoA synthetase family member 2 (ACSF2)[3].
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| ln Vivo |
Ferroptosis-induced animal models can be created with Erastin. In a mouse model of endometriosis, Erastin (40 mg/kg; i.p.; every 3 days for 2 weeks) inhibits endometriotic implantation, indicating that Erastin promotes regression of ectopic lesions by inducing ferroptosis [1]. In SCID mice, eratin (10 mg/kg, 30 mg/kg; intraperitoneally; once daily for 4 weeks) suppresses the growth of HT-29 xenografts, with 30 mg/kg showing the greatest activity [2].
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| Enzyme Assay |
Erastin inhibits voltage-dependent anion channels (VDAC2/VDAC3) and accelerates oxidation, leading to the accumulation of endogenous reactive oxygen species.
We here evaluated the potential anti-colorectal cancer activity by erastin, a voltage-dependent anion channel (VDAC)-binding compound. Our in vitro studies showed that erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells, which was evidenced by VDAC-1 and cyclophilin-D (Cyp-D) association, mitochondrial depolarization, and cytochrome C release. Caspase inhibitors, the ROS scavenger MnTBAP, and mPTP blockers (sanglifehrin A, cyclosporin A and bongkrekic acid), as well as shRNA-mediated knockdown of VDAC-1, all significantly attenuated erastin-induced cytotoxicity and apoptosis in colorectal cancer cells. On the other hand, over-expression of VDAC-1 augmented erastin-induced ROS production, mPTP opening, and colorectal cancer cell apoptosis. In vivo studies showed that intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Together, these results demonstrate that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. Erastin may be further investigated as a novel anti-colorectal cancer agent. |
| Cell Assay |
Cell Viability Assay[1]
Cell Types: Normal endometrial stromal cells (NESCs) and endometrial stromal cells (EESCs) Tested Concentrations: 0, 0.5, 0.8, 1, 1.5, 2, 2.5, 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced cell detachment and overt death in EESCs, but not NESCs. Apoptosis Analysis[1] Cell Types: EESCs infected with adenovirus expressing FPN cDNA (co-incubation for 24 hr) Tested Concentrations: 0, 0.5, 1.5, 2.5, 5 and 2.5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced ferroptosis by decreasing the levels of total ROS and lipid ROS. And reversed by the overexpression of FPN in adenovirus-infected cells. |
| Animal Protocol |
Animal/Disease Models: Mouse model of endometriosis[1]
Doses: 40 mg/kg Route of Administration: intraperitoneal (ip)injection; once every 3 days for 2 weeks Experimental Results: demonstrated little impact on body weight of mice and hair of mice displayed neat and glossy. decreased the volume of ectopic lesions. Mouse model of endometriosis[1] Ten C57BL/6 female mice (7–8 weeks, weight 20–22 g) were used. Endometriotic lesions were surgically induced by autotransplantation of uterine horns onto the peritoneal wall as previously described. Briefly, uterine horns were removed and opened longitudinally, cut into homogeneous fragments using a 3-mm dermal biopsy punch and then transplanted onto own peritoneal wall of mice by suturing. 17-β-Estradiol-3-benzoate (30 μg/kg) was administered to each postoperative mouse every 3 days for 28 days. At 14 day after operation, endometrial-like lesions were established, and it was time for intervention. They were randomly divided into two groups. In the experimental group, each mouse received erastin (40 mg/kg) by intraperitoneal injection over a 14-day period. In the control group, in place of erastin, soybean oil was used. At 28 days, the mice were sacrificed and we harvested the ectopic tissues. The volumes of ectopic lesions were measured and analyzed as previously described (Zhao et al., 2015). |
| References | |
| Additional Infomation |
Erastin is a member of the class of quinazolines that is quinazolin-4(3H)-one in which the hydrogens at positions 2 and 3 are replaced by 1-{4-[(4-chlorophenoxy)acetyl]piperazin-1-yl}ethyl and 2-ethoxyphenyl groups, respectively. It is an inhibitor of voltage-dependent anion-selective channels (VDAC2 and VDAC3) and a potent ferroptosis inducer. It has a role as a ferroptosis inducer, an antineoplastic agent and a voltage-dependent anion channel inhibitor. It is a member of quinazolines, a member of monochlorobenzenes, an aromatic ether, a N-acylpiperazine, a N-alkylpiperazine, a diether and a tertiary carboxamide.
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| Molecular Formula |
C30H31CLN4O4
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|---|---|---|
| Molecular Weight |
547.04
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| Exact Mass |
546.203
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| Elemental Analysis |
C, 65.87; H, 5.71; Cl, 6.48; N, 10.24; O, 11.70
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| CAS # |
571203-78-6
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| Related CAS # |
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| PubChem CID |
11214940
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| Appearance |
White to off-white solid
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
721.9±70.0 °C at 760 mmHg
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| Flash Point |
390.4±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.634
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| LogP |
4.75
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
871
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])C(N1C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C([H])(C([H])([H])[H])C1=NC2=C([H])C([H])=C([H])C([H])=C2C(N1C1=C([H])C([H])=C([H])C([H])=C1OC([H])([H])C([H])([H])[H])=O)=O
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| InChi Key |
BKQFRNYHFIQEKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H31ClN4O4/c1-3-38-27-11-7-6-10-26(27)35-29(32-25-9-5-4-8-24(25)30(35)37)21(2)33-16-18-34(19-17-33)28(36)20-39-23-14-12-22(31)13-15-23/h4-15,21H,3,16-20H2,1-2H3
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| Chemical Name |
2-(1-(4-(2-(4-chlorophenoxy)acetyl)piperazin-1-yl)ethyl)-3-(2-ethoxyphenyl)quinazolin-4(3H)-one
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| Synonyms |
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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 Note: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 1 mg/mL (1.83 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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. View More
Solubility in Formulation 3: 5% DMSO+corn oil: 2.5mg/mL Solubility in Formulation 4: 5 mg/mL (9.14 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8280 mL | 9.1401 mL | 18.2802 mL | |
| 5 mM | 0.3656 mL | 1.8280 mL | 3.6560 mL | |
| 10 mM | 0.1828 mL | 0.9140 mL | 1.8280 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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