| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
JAK2
Janus kinase 2 (JAK2). As a PROTAC, SJ1008030 TFA induces selective degradation of the JAK2 protein rather than simple enzymatic inhibition. It also shows dose-dependent degradation of other proteins including GSPT1 and IKZF1 in MHH-CALL-4 cells. The compound targets JAK2 for ubiquitination and subsequent proteasomal destruction. |
|---|---|
| ln Vitro |
Compound 8 (SJ1008030) TFA (72 hours) exhibits action with an IC50 of 5.4 nM in the CRLF2r cell line (MHH-CALL-4)[1]. (0-4.3 μM; 72 hours) SJ1008030 TFA causes dose-dependent degradation of JAK, GSPT1, and IKZF1 in MHH-CALL-4 cells [1]. The JAK-STAT signaling pathway is inhibited in xenografted bone marrow cells SJBALL021415 when SJ1008030 (0-10 μM; 24h) TFA dose-dependently degrades JAK2 and GSPT1 proteins [1].
In vitro, SJ1008030 TFA exhibits potent activity against MHH-CALL-4 (CRLF2r) cells with an IC50 of 5.4 nM after 72 hours of treatment. At concentrations ranging from 0-4.3 uM for 72 hours, it causes dose-dependent degradation of JAK2, GSPT1, and IKZF1 proteins in MHH-CALL-4 cells. The compound shows selective antiproliferative activity in leukemia cells and is inactive in normal cells. |
| ln Vivo |
In vivo efficacy data for SJ1008030 TFA are limited. As a PROTAC targeting JAK2, the compound is designed to achieve sustained target degradation in vivo. Based on its potent in vitro activity in CRLF2r leukemia cells and the known role of JAK2 in leukemia pathogenesis, SJ1008030 TFA is expected to show antitumor activity in xenograft models of JAK2-driven leukemia. Further in vivo studies are needed.
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| Enzyme Assay |
Non-cell-based JAK2 degradation assay (in vitro ubiquitination assay): Purified JAK2 protein is incubated with E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme, CRL2 E3 ligase complex, and increasing concentrations of SJ1008030 TFA (0-1000 nM) in reaction buffer containing ATP. The reaction proceeds at 37degC for 60 min. Ubiquitinated JAK2 is detected by Western blotting using anti-ubiquitin antibody or anti-JAK2 antibody. DC50 is determined by densitometry quantification.
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| Cell Assay |
Cell proliferation and degradation assay protocol: MHH-CALL-4 leukemia cells are seeded in 96-well plates (10,000 cells/well) and treated with SJ1008030 TFA at concentrations of 0-4.3 uM for 72 hours. Cell viability is measured using CellTiter-Glo or MTT assay. For degradation studies, cells are treated with SJ1008030 TFA (0-1000 nM) for 24-72 hours, then lysed and subjected to SDS-PAGE and Western blotting with antibodies against JAK2, GSPT1, and IKZF1. IC50/DC50 values are calculated by non-linear regression.
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| Animal Protocol |
Xenograft leukemia model protocol (suggested): Female NSG mice (6-8 weeks old) are intravenously injected with MHH-CALL-4-luciferase cells (1×10⁶ cells/mouse). After engraftment (detected by bioluminescence imaging), mice are randomized into treatment groups (n=6-8). SJ1008030 TFA is administered via intraperitoneal injection at 1-25 mg/kg, daily or every other day for 14-21 days. Tumor burden is monitored weekly by bioluminescence imaging. At study termination, bone marrow and spleen are harvested for flow cytometry analysis and protein degradation assessment.
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| ADME/Pharmacokinetics |
PK data for SJ1008030 TFA are limited. As a PROTAC with molecular weight of 987.96, the compound has moderate solubility in DMSO (125 mg/mL). The TFA salt form enhances aqueous solubility compared to the free base. In vivo pharmacokinetic properties including half-life, clearance, and bioavailability are likely to be determined in ongoing research studies. Formulation for in vivo studies typically involves DMSO/PEG300/Tween-80/saline mixtures.
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| Toxicity/Toxicokinetics |
Toxicity data for SJ1008030 TFA are limited. In vitro studies show potent antiproliferative activity against leukemia cells with IC50 of 5.4 nM. As a JAK2 degrader, potential toxicities may include effects on normal hematopoietic cells. The compound is intended for research use only and not for human therapeutic applications. The product has not been fully validated for medical applications. Standard safety precautions for handling chemical compounds should be observed.
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| References | |
| Additional Infomation |
SJ1008030 TFA is a research compound that has not entered clinical trials or received regulatory approval for human use. It represents a novel PROTAC-based approach to target JAK2 for degradation rather than inhibition, which may overcome resistance mutations and provide sustained target suppression. The compound is specifically designed for CRLF2-rearranged acute lymphoblastic leukemia research. Reference for the compound: Chang et al. (2021) in Blood.
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| Molecular Formula |
C44H44F3N13O9S
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|---|---|
| Molecular Weight |
987.96
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| Exact Mass |
987.306
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| CAS # |
2863634-97-1
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| Related CAS # |
SJ1008030 formic;SJ1008030;2863634-96-0
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| PubChem CID |
168475845
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
5
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
70
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| Complexity |
2010
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCS(=O)(=O)N1CC(C1)(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC(=N3)NC5=CC=C(C=C5)C(=O)NCCN6CCN(CC6)C7=CC8=C(C=C7)C(=O)N(C8=O)C9CCC(=O)NC9=O.C(=O)(C(F)(F)F)O
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| InChi Key |
RRJQTSMHAOAMTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C42H43N13O7S.C2HF3O2/c1-2-63(61,62)53-24-42(25-53,12-13-43)54-23-27(22-46-54)35-31-11-14-44-36(31)50-41(49-35)47-28-5-3-26(4-6-28)37(57)45-15-16-51-17-19-52(20-18-51)29-7-8-30-32(21-29)40(60)55(39(30)59)33-9-10-34(56)48-38(33)58;3-2(4,5)1(6)7/h3-8,11,14,21-23,33H,2,9-10,12,15-20,24-25H2,1H3,(H,45,57)(H,48,56,58)(H2,44,47,49,50);(H,6,7)
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| Chemical Name |
4-[[4-[1-[3-(cyanomethyl)-1-ethylsulfonylazetidin-3-yl]pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-[2-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperazin-1-yl]ethyl]benzamide;2,2,2-trifluoroacetic acid
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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 | 1.0122 mL | 5.0609 mL | 10.1219 mL | |
| 5 mM | 0.2024 mL | 1.0122 mL | 2.0244 mL | |
| 10 mM | 0.1012 mL | 0.5061 mL | 1.0122 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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