| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
ALK degrader 1 (compound H7) (72 hours) showed antiproliferative activity in ALK-dependent cell lines, with an IC50 of 0.23 μM in H3122 cells and 0.19 μM in Karpas 299 cells[1]. ALK degrader 1 (0.5-5 μM, 24 hours) can effectively degrade EML4-ALK in H3122 cells, achieving more than 80% degradation at 0.5 μM; while its degradation activity against NPM-ALK in Karpas 299 cells is relatively weak, with a degradation rate of about 70% at 5 μM[1]. ALK degrader 1 (0.1-5 μM, 2-24 hours) is a potent EML4-ALK degrader (DC50 = 0.13 μM) with rapid and sustained degradation properties, which can effectively inhibit ALK phosphorylation and downstream STAT3 signaling pathway in H3122 cells [1]. ALK degrader 1 (2 μM, 24 hours) can maintain the degradation effect of EML4-ALK for up to 48 hours after withdrawal [1]. ALK degrader 1 (0.5-2 μM, 24 hours) can effectively inhibit the mitotic process in H3122 cells, induce G0/G1 phase arrest, and thus induce apoptosis [1]. ALK degrader 1 (2 μM, 24 h) upregulated ALK mRNA expression and promoted the binding of ALK to Hsp70. Its degradation was significantly inhibited by MG-132, indicating that the degradation process depends on the ubiquitin-proteasome system [1]. ALK degrader 1 (0.1-1 μM, 72 h) showed good selectivity for ALK-negative tumor cells (A549) and normal lung epithelial fibroblasts (HFL-1) and had no obvious toxic side effects, indicating that it has good safety [1].
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| ln Vivo |
ALK degrader 1 (20 mg/kg, intravenous injection, single dose) can effectively degrade EML4-ALK protein in tumor tissue in the H3122 xenograft model [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: H3122 and Karpas 299 cells Tested Concentrations: 0.5, 1, and 5 μM Incubation Duration: 24 h Experimental Results: Effectively degraded EML4-ALK in H3122 cells at 5 μM after 24 h. Exhibited substantial EML4-ALK degradation efficacy even at 0.5 μM, with more than 80 % reduction observed in Karpas 299 cells. Showed reduced degradation activity against NPM-ALK in Karpas 299 cells compared to its activity against EML4-ALK in H3122 cells. Demonstrated appreciable NPM-ALK degradation in Karpas 299 cells, achieving approximately 70 % degradation at 5 μM. Western Blot Analysis[1] Cell Types: H3122 cells Tested Concentrations: 0.1, 0.5, 1, 2, and 5 μM Incubation Duration: 2, 4, 8, 16, 24 h Experimental Results: Exhibited a concentration-dependent ability to degrade EML4-ALK in H3122 cells, with complete degradation observed and a DC50 of 0.13 μM. Significant reduced ALK levels in H3122 cells at 0.5, 1 and 2 μM for 24 h. Decreased ALK phosphorylation in H3122 cells at 0.1 μM. Decreased p-STAT3 levels but did not change STAT3 levels in H3122 cells. (2 μM)Induced effective and sustained degradation of EML4-ALK in H3122 cells, reaching approximately 30 % at 2 h, peaking by 4 h, maintaining suppression to 23 % at 24 h. Western Blot Analysis[1] Cell Types: H3122 cells Tested Concentrations: 2 μM Incubation Duration: 24 h Experimental Results: Maintained low EML4-ALK levels for 48 hours after removal. Cell Cycle Analysis[1] Cell Types: H3122 cells Tested Concentrations: 0.5, 1, and 2 μM Incubation Duration: 24 h Experimental Results: Significantly increased the G0/G1 phase cell population and reduced the G2 phase population compared to control after 24 h at 2 μM. Significantly increased the sub-G0 phase cell population. Apoptosis Analysis[1] Cell Types: H3122 cells Tested Concentrations: 0.5, 1, and 2 μM Incubation Duration: 24 h Experimental Results: Increased the proportion of apoptotic cells from 9.41 % to 21.07 % after 24 h at 2 μM. Cell Proliferation Assay[1] Cell Types: H3122, HFL-1 and A549 cells. Tested Concentrations: 0.1, 0.5, and 1 μM Incubation Duration: 72 h Experimental Results: Inhibited H3122 cell proliferation by 30 % at 0.1 μM, while the inhibition rates for A549 and HFL-1 cells were 14 % and 12 %, respectively. Iinhibited the proliferation of over 80 % of H3122 cells at 0.5 μM, but showed minimal activity against HFL-1 and A549 cells. Exhibited a 90 % inhibition rate against H3122 cells at 1 μM, while its toxicity toward HFL-1 and A549 cells remained very low. |
| Animal Protocol |
Animal/Disease Models: Female BALB/c nude mice (4 weeks old) subcutaneously inoculated with H3122 cells[1]
Doses: 20 mg/kg Route of Administration: i.v., once Experimental Results: Exhibited sustained EML4-ALK degradation, detectable by 12 hours post-treatment and achieving over 85 % by 36 hours. |
| References |
| Molecular Formula |
C39H47N5O2
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|---|---|
| Molecular Weight |
617.82
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| Appearance |
Typically exists as solids at room temperature
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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 | 1.6186 mL | 8.0930 mL | 16.1859 mL | |
| 5 mM | 0.3237 mL | 1.6186 mL | 3.2372 mL | |
| 10 mM | 0.1619 mL | 0.8093 mL | 1.6186 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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