| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
SBI-0640756 targets eukaryotic translation initiation factor 4 gamma 1 (eIF4G1), a scaffolding protein that is essential for the assembly of the eIF4F translation initiation complex. By binding directly to eIF4G1, the compound disrupts the eIF4F complex, thereby inhibiting cap-dependent translation initiation. This disruption is not regulated by mTOR signaling. SBI-0640756 also suppresses AKT and NF-κB signaling, which are downstream of eIF4F complex function. The compound's mechanism of action involves inhibition of protein synthesis in cancer cells.
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| ln Vitro |
SBI-0640756 (SBI-756) is an eIF4G1 inhibitor that is soluble in water. In parental and BRAFi-resistant melanomas, eIF4F complexes are disrupted by SBI-0640756 (SBI-756) (0-1 μM). SBI-0640756 (SBI-756) suppresses AKT, NF-κB, and AKT/mTORC1 activities in addition to having inhibitory effects on human melanoma lines [1].
In vitro, SBI-0640756 acts as an inhibitor of eIF4G1 and disrupts the eIF4F complex. It suppresses AKT and NF-κB signaling. The compound reduces the growth rate of BRAF-resistant and BRAF-dependent melanoma. SBI-0640756 has been shown to inhibit protein synthesis and induce apoptosis in cancer cells. Its ability to disrupt the eIF4F complex and inhibit downstream signaling pathways has been demonstrated in various cancer cell lines. The compound is water-soluble, facilitating its use in in vitro studies. |
| ln Vivo |
SBI-0640756 (SBI-756) (0.5 mg/kg, i.p.) 50% decreased tumor incidence and delayed carcinogenesis in the NrasQ61K/Ink4a–/– genetic model. When used in conjunction with a BRAF inhibitor, SBI-0640756 (SBI-756) (1 mg/kg, twice weekly, i.p.) efficiently suppresses the growth of existing tumors without turning immunodeficient mice bearing A375 tumors back into normal. of tumor development [1].
In vivo, SBI-0640756 has demonstrated anti-tumor efficacy in preclinical models. It reduces the growth rate of BRAF-resistant and BRAF-dependent melanoma. However, specific in vivo experimental details are limited in the available literature. As a first-in-class inhibitor of eIF4G1, SBI-0640756 represents a novel therapeutic approach for targeting translation initiation in cancer. The compound's ability to suppress AKT and NF-κB signaling further supports its potential for treating cancers with dysregulated signaling pathways. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for SBI-0640756 are not typically performed because the compound targets a protein-protein interaction rather than an enzyme or receptor. However, the compound's ability to bind to eIF4G1 can be assessed using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The disruption of the eIF4F complex can be assessed using co-immunoprecipitation or pull-down assays.
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| Cell Assay |
In vitro cellular assays for SBI-0640756 are performed using cancer cell lines, including melanoma cells. Cells are treated with varying concentrations of SBI-0640756, and cell viability is measured using MTT or CellTiter-Glo assays. Protein synthesis is assessed by measuring the incorporation of labeled amino acids (e.g., [35S]methionine) or using puromycin-based assays (e.g., SUnSET). The disruption of the eIF4F complex is assessed by co-immunoprecipitation. AKT and NF-κB signaling are assessed by Western blotting. Apoptosis is evaluated using annexin V staining or caspase activity assays.
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| Animal Protocol |
In vivo animal experiments for SBI-0640756 are conducted in xenograft mouse models of melanoma or other cancers. Immunocompromised mice are implanted with human tumor cells and treated with SBI-0640756 via oral or intraperitoneal administration. Tumor growth inhibition is monitored, and endpoints include tumor volume, tumor weight, and survival. Pharmacodynamic markers such as eIF4F complex disruption, AKT and NF-κB signaling, and apoptosis in tumor tissues are assessed.
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| ADME/Pharmacokinetics |
SBI-0640756 has a molecular weight of 404.82 g/mol and a molecular formula of C23H14ClFN2O2. The compound is water-soluble and is soluble in DMSO at concentrations up to 80 mg/mL (197.61 mM). Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been extensively reported. As a first-in-class inhibitor, further pharmacokinetic studies would be necessary to support its development as a therapeutic agent.
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| Toxicity/Toxicokinetics |
The toxicological profile of SBI-0640756 has not been extensively characterized in publicly available literature. As a translation inhibitor, SBI-0640756 may have potential toxicity to normal cells, particularly those with high rates of protein synthesis. Standard toxicology studies, including assessment of cytotoxicity in normal cell lines and acute toxicity in animal models, would be necessary to establish its safety profile. No significant toxicity has been reported in the available literature.
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| References | |
| Additional Infomation |
SBI-0640756 is a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex. It also suppresses AKT and NF-κB signaling. The compound reduces the growth rate of BRAF-resistant and BRAF-dependent melanoma. SBI-0640756 is water-soluble and is a research compound for studying translation initiation in cancer. It is not an approved drug and requires further development for clinical use.
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| Molecular Formula |
C23H14CLFN2O2
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| Molecular Weight |
404.820868015289
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| Exact Mass |
404.072
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| CAS # |
1821280-29-8
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| PubChem CID |
121241171
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
701
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2=C(C=1)C(C1C=CC=CC=1)=C(C(C=CC1C=NC=C(C=1)F)=O)C(N2)=O
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| InChi Key |
VVWGPQZBDQVQRC-RMKNXTFCSA-N
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| InChi Code |
InChI=1S/C23H14ClFN2O2/c24-16-7-8-19-18(11-16)21(15-4-2-1-3-5-15)22(23(29)27-19)20(28)9-6-14-10-17(25)13-26-12-14/h1-13H,(H,27,29)/b9-6+
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| Chemical Name |
6-chloro-3-[(E)-3-(5-fluoropyridin-3-yl)prop-2-enoyl]-4-phenyl-1H-quinolin-2-one
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| Synonyms |
SBI0640756; SBI 0640756; SBI-0640756
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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 : ≥ 26 mg/mL (~64.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (12.35 mM) in 50% PEG300 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (6.18 mM) in 0.5% CMC-Na/saline water (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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4702 mL | 12.3512 mL | 24.7023 mL | |
| 5 mM | 0.4940 mL | 2.4702 mL | 4.9405 mL | |
| 10 mM | 0.2470 mL | 1.2351 mL | 2.4702 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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