| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Bruton's Tyrosine Kinase (BTK) and Cereblon (CRBN). SJF620 is a heterobifunctional PROTAC that simultaneously binds to BTK via its kinase inhibitor-based warhead and to the E3 ubiquitin ligase Cereblon (CRBN) via its lenalidomide analog. This induced proximity leads to the ubiquitination of BTK, marking it for degradation by the proteasome. Unlike inhibitors which only block kinase activity, SJF620 eliminates the entire BTK protein, disrupting both enzymatic and scaffolding functions.
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| ln Vitro |
In cellular studies, SJF620 is a PROTAC that maintains effective BTK degradation, with a DC50 of 7.9 nM in the Burkitt's lymphoma cell line NAMALWA [1].
In NAMALWA cells (a Burkitt lymphoma cell line), SJF620 demonstrates potent degradation of BTK in cellular assays with a DC₅0 (concentration for 50% degradation) of 7.9 nM. This confirms that the PROTAC is highly effective at very low concentrations, leading to the rapid and sustained depletion of BTK protein and resulting in the blockage of downstream survival pathways, thereby inducing apoptosis in BTK-dependent cancer cells. |
| ln Vivo |
SJF620 has better pharmacokinetic properties in mice (1 mg/kg; iv) with a half-life (t1/2) of 1.64 hours. The pharmacokinetic properties of SJF620 are much superior than those of MT802[1].
SJF620 has a superior pharmacokinetic profile in mice compared to MT802. When administered intravenously (i.v.) at 1 mg/kg, SJF620 has a half-life (t1/2) of 1.64 hours. This improved PK profile suggests better systemic stability and exposure, making it a more promising candidate for in vivo studies of BTK degradation. The improved PK likely translates to sustained target engagement and robust efficacy in animal models of leukemia/lymphoma. |
| Enzyme Assay |
Cell-free assays are not standard for PROTACs as activity requires the ternary complex formation. Target engagement is typically confirmed via a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) ternary complex formation assay, where recombinant biotin-labeled BTK, GST-labeled CRBN, and SJF620 are mixed. If the PROTAC engages both proteins, a signal is produced.
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| Cell Assay |
NAMLWA cells (human Burkitt‘s lymphoma line) are seeded in 6-well plates and treated with increasing concentrations of SJF620 (0.001-1 microM) for 24 hours. Cells are collected, lysed, and protein concentration is normalized. Lysates are resolved by SDS-PAGE, transferred to membranes, and immunoblotted with anti-BTK antibody and anti-beta-actin as a loading control. The DC₅0 (concentration for 50% degradation) is determined by densitometry analysis. Cell viability is assessed by CCK-8 or MTT assay.
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| ADME/Pharmacokinetics |
SJF620 exhibits a superior pharmacokinetic profile in mice compared to MT802. A typical in vivo protocol involves male CD-1 mice (n=3) dosed intravenously (i.v.) with SJF620 at 1 mg/kg formulated in a vehicle (e.g., 10% DMSO/10% ethanol/30% PEG400/50% water). Blood samples are collected at various time points, and plasma concentrations are quantified by LC-MS/MS to calculate PK parameters. For efficacy studies, mice bearing NAMALWA xenografts would be treated with SJF620. S onlineIn mouse in vivo studies, SJF620 (1 mg/kg; i.v.) demonstrates a half-life (t1/2) of 1.64 hours, indicating a favorable pharmacokinetic profile compared to earlier BTK degraders. The compound has a molecular weight of 760.84 and is soluble in DMSO (100 mg/mL). Its high molecular weight, typical for PROTACs, suggests poor oral bioavailability, making intravenous or intraperitoneal administration the preferred routes for in vivo studies.
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| Toxicity/Toxicokinetics |
No specific toxicology data for SJF620 is detailed. However, BTK is critical for B-cell development and function, so on-target degradation would cause immunosuppression (B-cell depletion) in animals. This is a predictable, mechanism-based effect rather than specific chemical toxicity. In preliminary PK studies, i.v. administration at 1 mg/kg was well-tolerated. Standard safety precautions for handling potent PROTACs should be followed.
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| References | |
| Additional Infomation |
SJF620 is a research chemical and has not been approved for human clinical use. It is a next-generation BTK degrader built upon the backbone of earlier degraders like MT802. It is designed to overcome drug resistance mutations (specifically the C481S mutation) that render covalent BTK inhibitors like Ibrutinib ineffective. SJF620 serves as a valuable pharmacological tool to validate BTK degradation as a therapeutic modality for B-cell malignancies.
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| Molecular Formula |
C41H44N8O7
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|---|---|
| Molecular Weight |
760.8375
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| Exact Mass |
760.333
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| CAS # |
2376187-16-3
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| Related CAS # |
SJF620 hydrochloride;2821938-05-8
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| PubChem CID |
139466026
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| Appearance |
White to light yellow solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
56
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| Complexity |
1310
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC1C([H])=C([H])C2C(N(C([H])([H])C=2C=1[H])C1([H])C(N([H])C(C([H])([H])C1([H])[H])=O)=O)=O)C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N1C2C(=C(N([H])[H])N=C([H])N=2)C(C2C([H])=C([H])C(=C([H])C=2[H])OC2C([H])=C([H])C([H])=C([H])C=2[H])=N1
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| InChi Key |
UJJYPBWMGIPXOE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C41H44N8O7/c42-38-36-37(27-6-8-31(9-7-27)56-30-4-2-1-3-5-30)46-49(39(36)44-26-43-38)29-14-16-47(17-15-29)18-19-53-20-21-54-22-23-55-32-10-11-33-28(24-32)25-48(41(33)52)34-12-13-35(50)45-40(34)51/h1-11,24,26,29,34H,12-23,25H2,(H2,42,43,44)(H,45,50,51)
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| Chemical Name |
3-[6-[2-[2-[2-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]ethoxy]ethoxy]ethoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione
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| Synonyms |
SJF620 SJF-620
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~100 mg/mL (~131.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3143 mL | 6.5717 mL | 13.1434 mL | |
| 5 mM | 0.2629 mL | 1.3143 mL | 2.6287 mL | |
| 10 mM | 0.1314 mL | 0.6572 mL | 1.3143 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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