| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PROTAC FLT-3 degrader 1 targets FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase that is frequently mutated in acute myeloid leukemia (AML). The compound functions as a PROTAC that simultaneously binds to FLT3 and the E3 ubiquitin ligase VHL. This brings FLT3 into proximity with the ubiquitin-proteasome system, leading to its ubiquitination and subsequent proteasomal degradation. The compound targets both wild-type and mutant FLT3 proteins.
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|---|---|
| ln Vitro |
In vitro, PROTAC FLT-3 degrader 1 is a FLT-3 internal tandem duplication (ITD) degrader with an IC₅0 of 0.6 nM. It exhibits anti-proliferative activity and induces apoptosis. The compound's high potency and ability to degrade both wild-type and mutant FLT3 make it a valuable tool for studying FLT3 biology and for developing therapies for FLT3-driven AML.
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| ln Vivo |
In vivo studies of PROTAC FLT-3 degrader 1 are focused on evaluating its efficacy in animal models of FLT3-mutant AML. As a PROTAC degrader, the compound may offer advantages over conventional FLT3 inhibitors by inducing degradation of both wild-type and mutant FLT3 proteins. Further in vivo studies are needed to fully characterize its efficacy, safety, and pharmacokinetic profile.
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| Enzyme Assay |
For in vitro binding assays, PROTAC FLT-3 degrader 1 can be evaluated using binding studies to confirm its interaction with FLT3 and VHL. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be used to measure binding affinities. The compound's ability to induce ternary complex formation between FLT3 and VHL can be assessed using biophysical methods. Ubiquitination assays can be used to measure the compound-induced ubiquitination of FLT3.
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| Cell Assay |
For in vitro cellular experiments, PROTAC FLT-3 degrader 1 is tested in FLT3-mutant AML cell lines. Cells are cultured in appropriate media and treated with various concentrations of the compound. FLT3 protein levels are assessed by Western blotting or immunofluorescence to determine the extent of degradation. Cell viability and proliferation are assessed using standard assays. Apoptosis is evaluated using Annexin V staining or caspase activity assays.
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| Animal Protocol |
For in vivo animal experiments, PROTAC FLT-3 degrader 1 can be administered to tumor-bearing mice via various routes including intravenous injection or intraperitoneal injection. Xenograft models using FLT3-mutant AML cell lines are commonly used. Typical dosing regimens may range from 1 to 50 mg/kg. FLT3 protein levels in tumors are assessed by Western blotting or immunohistochemistry. Tumor volume, body weight, and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PROTAC FLT-3 degrader 1 are not extensively detailed in the public literature. As a PROTAC molecule with a molecular weight of 1020.23, it may have limited oral bioavailability and may require parenteral administration for in vivo studies. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for PROTAC FLT-3 degrader 1 are limited, as it is primarily a research tool. As a FLT3 degrader, its toxicity would depend on the importance of FLT3 signaling for normal hematopoiesis and immune function. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
PROTAC FLT-3 degrader 1 is a research compound used for targeted protein degradation studies. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a VHL-based FLT-3 ITD degrader with an IC₅0 of 0.6 nM.
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| Molecular Formula |
C52H61N9O9S2
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|---|---|
| Molecular Weight |
1020.22564959526
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| Exact Mass |
1019.403
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| CAS # |
2230826-81-8
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| PubChem CID |
135172387
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| Appearance |
White to light yellow solid powder
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| LogP |
7.7
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
72
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| Complexity |
1800
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CCOCCOCCOC1C=CC2=C(C=1)SC1=NC(C3C=CC(=CC=3)NC(NC3C=C(C(C)(C)C)ON=3)=O)=CN21)=O)=O)O)=O
|
| InChi Key |
IKJBYQODYFQASC-YKCITUTQSA-N
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| InChi Code |
InChI=1S/C52H61N9O9S2/c1-31-45(71-30-54-31)34-10-8-32(9-11-34)27-53-47(64)40-24-36(62)28-60(40)48(65)46(52(5,6)7)58-44(63)18-19-67-20-21-68-22-23-69-37-16-17-39-41(25-37)72-50-56-38(29-61(39)50)33-12-14-35(15-13-33)55-49(66)57-43-26-42(70-59-43)51(2,3)4/h8-17,25-26,29-30,36,40,46,62H,18-24,27-28H2,1-7H3,(H,53,64)(H,58,63)(H2,55,57,59,66)/t36-,40+,46-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[3-[2-[2-[2-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]imidazo[2,1-b][1,3]benzothiazol-6-yl]oxyethoxy]ethoxy]propanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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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) |
DMSO : ~150 mg/mL (~147.03 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 7.5 mg/mL (7.35 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 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: 7.5 mg/mL (7.35 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 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: ≥ 7.5 mg/mL (7.35 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 | 0.9802 mL | 4.9009 mL | 9.8017 mL | |
| 5 mM | 0.1960 mL | 0.9802 mL | 1.9603 mL | |
| 10 mM | 0.0980 mL | 0.4901 mL | 0.9802 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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