| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
The primary targets of SNIPER(BRD)-1 include BRD4 (a bromodomain and extra-terminal domain protein), cIAP1, cIAP2, and XIAP (inhibitor of apoptosis proteins). The compound functions as a SNIPER (Specific and Non-genetic IAP-dependent Protein Eraser) that simultaneously binds to its target proteins and the E3 ubiquitin ligase activity of IAPs. By bridging BRD4 with IAPs, SNIPER(BRD)-1 induces ubiquitination and subsequent proteasomal degradation of BRD4. The compound also degrades cIAP1, cIAP2, and XIAP, with IC₅0 values of 6.8 nM, 17 nM, and 49 nM, respectively.
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| ln Vitro |
In vitro studies demonstrate that SNIPER(BRD)-1 is a novel and potent BRD4 degrader consisting of an IAP antagonist and a BET inhibitor linked together. The compound induces BRD4 degradation via the ubiquitin-proteasome pathway. It also degrades cIAP1, cIAP2, and XIAP with IC₅0 values of 6.8 nM, 17 nM, and 49 nM, respectively. By degrading both BRD4 and IAPs, the compound exerts potent antitumor effects through multiple mechanisms, including inhibition of BRD4-dependent transcription and activation of apoptosis pathways. SNIPER(BRD)-1 is a valuable tool for studying BRD4 and IAP biology.
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| ln Vivo |
In vivo studies of SNIPER(BRD)-1 are likely focused on evaluating its antitumor efficacy in animal models of cancers where BRD4 and IAPs play important roles. As a potent BRD4 and IAP degrader, the compound is expected to demonstrate significant tumor growth inhibition in vivo. Its dual mechanism of action, targeting both BRD4-dependent transcription and IAP-mediated apoptosis, makes it a promising candidate for cancer therapy. Further in vivo studies are needed to fully characterize its pharmacokinetic properties, bioavailability, and efficacy in various cancer models.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, SNIPER(BRD)-1 can be evaluated using binding studies to confirm its interaction with BRD4 and IAPs. 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 BRD4 and IAPs can be assessed using biophysical methods. Ubiquitination assays can be used to measure the compound-induced ubiquitination of BRD4 and IAPs. Standard assay conditions include physiological buffer systems with appropriate pH and ionic strength. Dose-response curves are generated to determine binding affinities and degradation potency.
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| Cell Assay |
For in vitro cellular experiments, SNIPER(BRD)-1 is tested in cell lines expressing BRD4 and IAPs to evaluate its degradation efficacy. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). BRD4, cIAP1, cIAP2, and XIAP protein levels are assessed by Western blotting or immunofluorescence. The kinetics and dose-dependence of degradation are characterized. Downstream effects on cell signaling, gene expression, and cell function are evaluated. Cell viability, proliferation, and apoptosis are assessed using standard assays. The compound's effects on apoptosis pathways are of particular interest due to its IAP degradation activity.
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| Animal Protocol |
For in vivo animal experiments, SNIPER(BRD)-1 can be administered to tumor-bearing mice via various routes including intravenous injection or intraperitoneal injection, depending on its solubility and pharmacokinetic properties. Xenograft models using human cancer cell lines that are sensitive to BRD4 or IAP inhibition are commonly used. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Tumor volume is measured regularly, and tumor growth inhibition is calculated. BRD4 and IAP protein levels in tumors are assessed by immunohistochemistry or Western blotting. Apoptosis markers are measured. Body weight and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SNIPER(BRD)-1 are not extensively detailed in the public literature. As a large molecule with a molecular weight of 1056.73 g/mol, it may have limited oral bioavailability and may require parenteral administration for in vivo studies. The compound's solubility and stability in biological fluids would influence its pharmacokinetic profile. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for SNIPER(BRD)-1 are limited, as it is primarily a research tool. As a degrader of BRD4 and IAPs, its toxicity would depend on the importance of these proteins for normal cellular function. BRD4 is a key epigenetic regulator, and IAPs are important for cell survival. Their degradation could have significant effects on normal tissues. Comprehensive toxicology studies would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
SNIPER(BRD)-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 novel and potent BRD4 degrader consisting of an IAP antagonist and a BET inhibitor. It induces BRD4 degradation via the ubiquitin-proteasome pathway and also degrades cIAP1, cIAP2, and XIAP with IC₅0 values of 6.8 nM, 17 nM, and 49 nM.
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| Molecular Formula |
C53H66CLN9O8S2
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|---|---|
| Molecular Weight |
1056.72964906693
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| Exact Mass |
1055.416
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| CAS # |
2095244-54-3
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| PubChem CID |
138377573
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
73
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| Complexity |
1830
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| Defined Atom Stereocenter Count |
4
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| SMILES |
ClC1C=CC(=CC=1)C1C2C(C)=C(C)SC=2N2C(C)=NN=C2[C@H](CC(NCCOCCOCCOCCOC2=CC=CC(=C2)C(C2=CSC([C@@H]3CCCN3C([C@H](C3CCCCC3)NC([C@H](C)NC)=O)=O)=N2)=O)=O)N=1
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| InChi Key |
FVDSZRCRCFMYQV-CDYWKMCDSA-N
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| InChi Code |
InChI=1S/C53H66ClN9O8S2/c1-32-34(3)73-53-45(32)46(37-16-18-39(54)19-17-37)57-41(49-61-60-35(4)63(49)53)30-44(64)56-20-22-68-23-24-69-25-26-70-27-28-71-40-14-9-13-38(29-40)48(65)42-31-72-51(58-42)43-15-10-21-62(43)52(67)47(36-11-7-6-8-12-36)59-50(66)33(2)55-5/h9,13-14,16-19,29,31,33,36,41,43,47,55H,6-8,10-12,15,20-28,30H2,1-5H3,(H,56,64)(H,59,66)/t33-,41-,43-,47-/m0/s1
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| Chemical Name |
(2S)-N-[(1S)-2-[(2S)-2-[4-[3-[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]benzoyl]-1,3-thiazol-2-yl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)propanamide
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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 : ~66.67 mg/mL (~63.09 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.37 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 (2.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9463 mL | 4.7316 mL | 9.4632 mL | |
| 5 mM | 0.1893 mL | 0.9463 mL | 1.8926 mL | |
| 10 mM | 0.0946 mL | 0.4732 mL | 0.9463 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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