| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
TAS1440 benzoate is a highly selective histone H3 competitive inhibitor that inhibits purified recombinant human LSD1 with an IC50 value of 4.8 nM. It has no significant activity against LSD2, MAO-A, MAO-B, or various other epigenetic enzymes [1]. TAS1440 (0-7500 nM; 8 days) benzoate selectively inhibits the proliferation of SCLC-A cell lines, with the strongest inhibitory efficacy against NCI-H1417, NCI-H510A, NCI-H146, and COR-L51 cells, and exhibits stronger antiproliferative activity than covalent LSD1 inhibitors in these sensitive models [1]. TAS1440 (300 nM; 1-7 days) benzoate can induce transcriptional reprogramming in small cell lung cancer (SCLC) cell lines, activate the tumor suppressor TGF-β and NOTCH signaling pathways, and inhibit the expression of neuroendocrine genes, with the most significant changes in TAS1440-sensitive SCLC-A cell lines [1]. TAS1440 (300 nM; 30 min-5 days) benzoate activates the TGF-β and NOTCH signaling pathways in SCLC-A cell lines by inducing SMAD2 phosphorylation, NOTCH1 upregulation, and accumulation of active pathway components in the cell nucleus. At the same time, its efficiency in disrupting the INSM1-LSD1 and SMAD2-LSD1 protein complex is also higher than that of covalent LSD1 inhibitors [1]. TAS1440 (300 nM; 5 days) benzoate can induce global epigenetic reprogramming in SCLC-A cell lines, increase active histone modifications (H3K4me1, H3K4me2, H3K27ac) at the transcription start site (TSS), and promote the binding of INSM1 and SMAD2 to the promoters of tumor suppressor genes NOTCH and TGF-β pathway genes [1]. The antiproliferative and transcriptional effects of TAS1440 (100–3,000 nM; 7 days) benzoate in SCLC-A cell lines depend on the expression and catalytic activity of LSD1, while its ability to disrupt the INSM1/SMAD2-LSD1 complex is independent of the catalytic function of LSD1 [1]. TAS1440 (300 nM; 2 hours–10 days) benzoate requires INSM1 to exert its antiproliferative, transcriptional reprogramming, and TGF-β/NOTCH signaling effects in SCLC-A cell lines [1].
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| ln Vivo |
TAS1440 (16.7-50 mg/kg/day; orally; once daily; for 3 weeks) benzoate significantly inhibited tumor growth in various SCLC-A subcutaneous xenograft models and activated the tumor suppressor NOTCH/TGF-β signaling pathway in xenograft tumors [1]. TAS1440 (50 mg/kg/day; orally; once daily; for 3 weeks) benzoate significantly inhibited tumor growth in INSM1 wild-type NCI-H146 SCLC-A xenograft models, but had no such effect on INSM1 knockout NCI-H146 SCLC-A xenograft models, indicating that the in vivo efficacy depended on INSM1 [1]. TAS1440 (50 mg/kg/day; orally; once daily; for 4 weeks) benzoate reduced the lung tumor burden by 67% in orthotopic NCI-H146 SCLC-A xenograft models [1].
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| Animal Protocol |
Animal/Disease Models:CB-17 SCID mice (male, 6 weeks old, subcutaneously injected with NCI-H1417, NCI-H146, NCI-H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
Doses: 16.7 mg/kg; 50 mg/kg Route of Administration: Oral; once daily for 3 weeks Experimental Results: Compared with the vector group, the growth of NCI-H1417 xenografts was significantly reduced in the 16.7 and 50 mg/kg/day dose groups. Compared with the vector group, the growth of NCI-H146, NCI-H510A and COR-L51 xenografts was significantly reduced in the 50 mg/kg/day dose group. In xenograft tumors, NOTCH1 expression is upregulated and phosphorylated SMAD2 (pSMAD2) levels are increased. It induces the expression of NOTCH/TGF-β pathway genes (NOTCH1, HES1, TGFB2, TGFBR2, ID3) and reduces the expression of ASCL1 and DLL3. Animal/Disease Models:CB-17 SCID mice (male, 6 weeks old, subcutaneously injected with NCI-H1417, NCI-H146, NCI-H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1] Doses: 50 mg/kg Route of Administration: Oral; once daily; for 3 weeks Experimental Results: Compared with the vector group, the growth of INSM1 wild-type NCI-H146 xenografts was significantly inhibited. The growth of INSM1 knockout NCI-H146 xenografts was not significantly affected. Animal/Disease Models:CB-17 SCID mice (male, 6 weeks old, subcutaneously injected with NCI-H1417, NCI-H146, NCI-H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1] Doses: 50 mg/kg Route of Administration: Oral; daily; 4 weeks Experimental Results: Lung tumor area was reduced by 67% compared with the vector, as measured by volumetric quantification by microCT. |
| References |
| Molecular Formula |
C35H33F2N3O4
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|---|---|
| Molecular Weight |
597.65
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| CAS # |
2642224-15-3
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
O=C(O)C1=CC=CC=C1.N[C@H](C2)CCN2C(C(C=C3C4=CC=C(C#N)C(F)=C4)=CC=C3C5=CC=C(C=C5F)CC(C)(C)O)=O
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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) |
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
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|---|---|
| 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 | 1.6732 mL | 8.3661 mL | 16.7322 mL | |
| 5 mM | 0.3346 mL | 1.6732 mL | 3.3464 mL | |
| 10 mM | 0.1673 mL | 0.8366 mL | 1.6732 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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