| ln Vitro |
PROTAC EML4-ALK Degrader-2 (compound B3) (72 hours) did not increase toxicity to normal human hepatocytes in the LO2 cell line and showed antiproliferative activity in H3122, H2228, H1299, A549 and HeLa cells, with IC50 values of 0.3, 0.9, 2.84, 1.6 and 1.18 μM, respectively [1]. PROTAC EML4-ALK Degrader-2 (0-50 nM, 0-32 hours) reduced the cellular level of ALK fusion protein in H3122 cells in a concentration- and time-dependent manner [1]. PROTAC EML4-ALK Degrader-2 (10-500 nM) showed high selectivity for ALK, maintained moderate inhibitory activity against IGF1R and INSR, but did not induce the degradation of IGF1R and INSR [1]. PROTAC EML4-ALK Degrader-2 is not effective against ALK resistance mutations: in BaF3-ALK-L1196M and BaF3-ALK-G1202R cells, its activity against BaF3-ALK-L1196M cells is slightly better than that against LDK378 [1].
|
|---|---|
| ln Vivo |
PROTAC EML4-ALK Degrader-2 (compound B3) (25-50 mg/kg, lateral wall, once daily for 15 days) was able to inhibit tumor growth in the H3122 xenograft model via dose-modulated therapy and had good safety [1].
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: H3122 cells Tested Concentrations: 0, 1, 5, 10, 20, 50 and 100 nM Incubation Duration: 0, 4, 8, 16, 24 and 32 h Experimental Results: Degraded ALK in a dose dependent manner for 8 h; effectively degraded ALK at 50 nM for 8 h; degraded all the ALK protein at 200 nM. Achieved amount (>80%) of EML4-ALK degradation after 16 h treatment at 100 nM. Not observed maximum degradation of EML4-ALK degradation until 24 h at 100 nM. Inhibited p-ALK and downregulated the level of p-STAT3 after 24 h at 100 nM. Induced ALK degradation in a concentration dependent manner after 24 h. Achieved maximum degradation of EML4-ALK degradation at 50 nM. Downregulated the level of p-ALK and p-STAT3 in a concentration dependent manner after 24 h. |
| Animal Protocol |
Animal/Disease Models: H3122 cells (5 x 106) induced-female BALB/c nude mice (6-7 weeks) (18-22g) [1]
Doses: 25, 50 mg/kg Route of Administration: o.p., once daily for 15 days Experimental Results: Observed tumor growth inhibitions (TGIs) of 37% and 48% at dose of 25 mg/kg and 50 mg/kg, respectively. Did not cause significant weight loss and toxicity. |
| References |
| CAS # |
2417174-28-6
|
|---|---|
| Appearance |
Typically exists as solids at room temperature
|
| 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.) |
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
Copyright 2020 InvivoChem LLC | All Rights Reserved
