| Size | Price | |
|---|---|---|
| 1mg | ||
| 5mg | ||
| Other Sizes |
| References | |
|---|---|
| Additional Infomation |
Zotatifin is being investigated in the clinical trial NCT04092673 (Eft226 in patients with specific advanced solid tumors). Zotatifin is a selective inhibitor of eukaryotic translation initiation factor 4A (eIF4A) with potential antitumor activity. After administration, Zotatifin targets and binds to eIF4A, promoting the binding of eIF4A to mRNAs containing specific polypurine motifs within the 5' untranslated region (5'-UTR), thereby forming a stable sequence-specific ternary complex (eIF4A-zotatifin-mRNA). This leads to the inhibition of translation of key oncogenes and anti-apoptotic proteins involved in tumor cell proliferation, survival, and metastasis, such as KRAS, Myc, myeloid leukemia-1 (Mcl-1), B-cell lymphoma-2 (Bcl-2), cyclin-dependent kinases (CDKs) 4 and 6, cyclin D, fibroblast growth factor receptor (FGFR) 1 and 2, human epidermal growth factor receptor 2 (HER2; ERBB2), and β-catenin. The inhibition of these oncogene expression results in the suppression of multiple oncogenic signaling pathways, thereby inhibiting tumor cell proliferation and inducing apoptosis. eIF4A is an RNA helicase and a rate-limiting component of the eukaryotic translation initiation complex. It catalyzes ATP-dependent RNA double-strand unwinding and promotes the scanning of 43S ribosomes within the 5' untranslated region (5'-UTR). eIF4A can be activated by multiple oncogenic signaling pathways, including the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and regulates the translation of oncogenes and tumor survival factors with complex secondary structures in the 5'-UTR. These genes and factors are essential for the proliferation, survival and metastasis of tumor cells.
|
| Molecular Formula |
C28H29N3O5
|
|---|---|
| Molecular Weight |
487.55
|
| Exact Mass |
487.21
|
| CAS # |
2098191-54-7
|
| Related CAS # |
Zotatifin;2098191-53-6
|
| PubChem CID |
129138801
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
36
|
| Complexity |
819
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C(#N)C1=CC=C([C@]23[C@H](C4=CC=CC=C4)[C@@H](CN(C)C)[C@@H](O)[C@@]2(O)C2=C(O3)C=C(OC)N=C2OC)C=C1
|
| InChi Key |
QYCXWOACFWMQFO-WZWZCULESA-N
|
| InChi Code |
InChI=1S/C28H29N3O5/c1-31(2)16-20-23(18-8-6-5-7-9-18)28(19-12-10-17(15-29)11-13-19)27(33,25(20)32)24-21(36-28)14-22(34-3)30-26(24)35-4/h5-14,20,23,25,32-33H,16H2,1-4H3/t20-,23-,25-,27+,28+/m1/s1
|
| Chemical Name |
4-[(2S,3R,4S,5S,6R)-4-[(dimethylamino)methyl]-2,3-dihydroxy-10,12-dimethoxy-5-phenyl-7-oxa-11-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-trien-6-yl]benzonitrile
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0511 mL | 10.2554 mL | 20.5107 mL | |
| 5 mM | 0.4102 mL | 2.0511 mL | 4.1021 mL | |
| 10 mM | 0.2051 mL | 1.0255 mL | 2.0511 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.
Products are for research use only; We do not sell to patients
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