| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
BCR-ABL fusion oncoprotein. SIAIS100 TFA functions as a PROTAC degrader, inducing ubiquitination and proteasomal degradation of the BCR-ABL protein with a DC50 of 2.7 nM. The compound specifically targets BCR-ABL for degradation, thereby inhibiting its kinase activity and downstream signaling pathways critical for CML cell proliferation and survival.
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| ln Vitro |
On K562 cells, SIAIS100 exhibits anti-proliferative action with an IC50 value of 12 nM[1]. BCR-ABL degraded at rates of 81.78% and 91.20%, respectively, at dosages of 5 nM and 100 nM of SIAIS100 [1]. BCR-ABL in K562 cells is considerably reduced by SIAIS100 (100 nM; 8 h)[1]. After the medication is removed, SIAIS100 (100 nM; 6 h) prolongs the cellular response while steadily and robustly degrading BCR-ABL [1]. While reducing BCR-ABL signaling (measured by p-BCR-ABL levels) in 32D cells, SIAIS100 (1-1000 nM) greatly reduced mutant G250E/T315I in a dose-dependent manner [1].
In vitro, SIAIS100 TFA is a potent BCR-ABL PROTAC degrader with a DC50 of 2.7 nM, used in chronic myeloid leukemia (CML) research. The compound exhibits antiproliferative activity against BCR-ABL-positive CML cell lines. By degrading the BCR-ABL fusion protein, SIAIS100 TFA effectively blocks downstream signaling pathways including STAT5, CRKL, and AKT, leading to reduced cell survival and proliferation. |
| ln Vivo |
In vivo efficacy data for SIAIS100 TFA are not detailed in available literature. As a potent BCR-ABL PROTAC degrader with a DC50 of 2.7 nM, the compound is expected to demonstrate antitumor activity in mouse xenograft models of chronic myeloid leukemia. The degradation approach may offer advantages over traditional kinase inhibitors by eliminating the entire oncoprotein rather than merely inhibiting its kinase activity.
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| Enzyme Assay |
BCR-ABL degradation assay protocol: Recombinant BCR-ABL protein or lysates from BCR-ABL-positive cells are incubated with increasing concentrations of SIAIS100 TFA (0-1000 nM) in the presence of E3 ligase components (CRBN), ubiquitin, E1, and E2 enzymes for 60 min at 37degC. The reaction is stopped with SDS-PAGE sample buffer. Ubiquitinated BCR-ABL and total BCR-ABL are detected by Western blotting using anti-BCR-ABL or anti-ubiquitin antibody. DC50 is determined by densitometry quantification.
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| Cell Assay |
Cell proliferation and degradation assay protocol: BCR-ABL-positive CML cells (e.g., K562 or KU812) are seeded in 96-well plates (10,000 cells/well) and treated with SIAIS100 TFA at concentrations of 0-1000 nM for 48-72 hours. Cell viability is measured using CellTiter-Glo or MTT assay. For degradation studies, cells are treated with SIAIS100 TFA (0-100 nM) for 24-48 hours, lysed, and analyzed by Western blotting for BCR-ABL protein levels and downstream signaling (p-STAT5, p-CRKL, p-AKT). DC50 is calculated by non-linear regression.
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| Animal Protocol |
Xenograft CML model protocol (suggested): Female NSG mice (6-8 weeks old) are intravenously injected with K562-luciferase cells (2×10⁶ cells/mouse). After engraftment (detected by bioluminescence imaging), mice are randomized into treatment groups (n=6-8). SIAIS100 TFA is administered via intraperitoneal injection or oral gavage at 1-25 mg/kg, once daily for 14-21 days. Tumor burden is monitored weekly by bioluminescence imaging. At study termination, spleen and bone marrow are harvested for flow cytometry, Western blotting, and histology.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for SIAIS100 TFA are limited. As a PROTAC (MW 918.91) with TFA salt form, the compound is formulated for in vivo studies using DMSO/PEG300/Tween-80/saline mixtures (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline). PK parameters including half-life, Cmax, AUC, and bioavailability should be determined in future studies by LC-MS/MS after intravenous or oral administration in rodents.
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| Toxicity/Toxicokinetics |
Toxicity data for SIAIS100 TFA are limited. The compound is intended for research use only and not for human therapeutic applications. As a BCR-ABL degrader, potential toxicities may include effects on normal hematopoietic stem cells. The compound should be handled with appropriate safety precautions in a laboratory setting. The TFA salt is stable; store powder at -20degC for long-term stability.
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| References | |
| Additional Infomation |
SIAIS100 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 for degrading the BCR-ABL oncoprotein, which is the driver of CML. Unlike tyrosine kinase inhibitors (e.g., imatinib) that only block kinase activity, PROTAC degraders eliminate the entire protein, potentially overcoming resistance mutations. SIAIS100 TFA is a valuable tool for studying BCR-ABL biology and resistance mechanisms.
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| Molecular Formula |
C46H51CLF5N9O7S
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| Molecular Weight |
1004.46
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| Related CAS # |
SIAIS100
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| Appearance |
White to off-white solid powder
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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 (~99.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.49 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 (2.49 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 (2.49 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 | 0.9956 mL | 4.9778 mL | 9.9556 mL | |
| 5 mM | 0.1991 mL | 0.9956 mL | 1.9911 mL | |
| 10 mM | 0.0996 mL | 0.4978 mL | 0.9956 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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