| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
PROTAC JAK2 degrader-1 (compound 10i) (8 nM-5 μM; 24 h) effectively degrades JAK2V617F protein in SET-2 cells via a proteasome-dependent pathway, with a DC50 of 27.35 nM and a degradation rate of up to 91.32% after 24 h of treatment with 5 μM [1]. PROTAC JAK2 degrader-1 (8 nM-5 μM; 24 h) inhibits the JAK2-STAT signaling pathway in SET-2 cells in a dose-dependent manner by reducing the phosphorylation levels of JAK2, STAT3 and STAT5 [1]. PROTAC JAK2 degrader-1 effectively inhibits the proliferation of SET-2 cells with an IC50 of 0.12 μM; at the same time, it can also inhibit the proliferation of HEL cells with an IC50 of 1.43 μM [1]. PROTAC JAK2 degrader-1 (0-1 μM, 24 h) blocks the G2/M cell cycle progression of SET-2 cells and induces apoptosis in a dose-dependent manner [1].
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| ln Vivo |
PROTAC JAK2 degrader-1 (30 mg/kg; intraperitoneal injection; daily; 4 days) effectively reduced erythrocyte polycythemia, splenomegaly, erythroid progenitor cell population and JAK2-STAT pathway activation in rhEPO-induced polycythemia mice [1].
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| Cell Assay |
Western Blot Analysis [1]
Cell Types: SET-2 cells (carrying JAK2 V617F mutation) Tested Concentrations: 8 nM, 40 nM, 200 nM, 1 μM, 5 μM Incubation Duration: 24 hours Experimental Results: In SET-2 cells, JAK2 V617F protein was induced to undergo dose-dependent degradation. The degradation rate was 15.12% at 8 nM, 56.91% at 40 nM, 76.45% at 200 nM, 78.40% at 1 μM, and 91.32% at 5 μM. The DC50 reached 27.35 nM. Dose-dependent inhibition of phosphorylation of JAK2, STAT3, and STAT5 in SET-2 cells had no significant effect on total STAT3 and STAT5 protein levels. Western Blot Analysis [1] Cell Types: Jurkat cells Tested Concentrations: 8 nM, 40 nM, 200 nM, 1 μM, 5 μM Incubation Duration: 24 hours Experimental Results: Even at the highest test concentration of 5 μM, JAK1, JAK3, TYK2, or GSPT1 did not show significant degradation in Jurkat cells. Cell cycle analysis [1] Cell Types: SET-2 cells Tested Concentrations: 0, 0.1, 1 μM Incubation Duration: 24 hours Experimental Experimental Results: Blocked G2/M cell cycle progression.
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| Animal Protocol |
Animal/Disease Models:BALB/c (female, 8-10 weeks old, 20-25 g, rhEPO-induced polycythemia and splenomegaly) [1]
Doses: 30 mg/kg Route of Administration: Intraperitoneal injection; once daily for 4 consecutive days Experimental Results: Reticulocyte count decreased from 18.25% (model group) to 10.94%. Hematocrit decreased from 49.80% (model group) to 44.81%. The proportion of Ter119/CD71 positive erythroid progenitor cells in the spleen decreased from 41.25% (model group) to 25.43%, and the proportion of Ter119/CD71 positive erythroid progenitor cells in the bone marrow decreased from 19.71% (model group) to 6.16%. The average spleen weight decreased from 0.269 g (model group) to 0.216 g. The level of JAK2 protein in spleen tissue was reduced, and the phosphorylation of STAT3 and STAT5 was inhibited. |
| References |
| Molecular Formula |
C45H51CLFN9O5
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|---|---|
| Molecular Weight |
852.40
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
FC1=CC([C@H](OC2=C(N=CC(C3=CN(N=C3)C4CCN(CC4)CC5CN(CC5)CC6CCN(CC6)C7=CC(C(N8C9CCC(NC9=O)=O)=O)=C(C=C7)C8=O)=C2)N)C)=C(C=C1)Cl
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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 | 1.1732 mL | 5.8658 mL | 11.7316 mL | |
| 5 mM | 0.2346 mL | 1.1732 mL | 2.3463 mL | |
| 10 mM | 0.1173 mL | 0.5866 mL | 1.1732 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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