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| 1mg | ||
| Other Sizes |
| Targets |
PROTAC BRD4 degrader for PAC-1 targets BRD4. It is a PROTAC-linker conjugate that incorporates the chimeric BET degrader GNE-987. The BRD4-targeting moiety in this compound is GNE-987, a highly potent BET degrader. This conjugate is designed for the selective degradation of the target protein, PAC-1, by first binding to and degrading BRD4.
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| ln Vitro |
In vitro, PROTAC BRD4 degrader for PAC-1 functions by specifically targeting and degrading the BRD4 protein. This PROTAC-linker conjugate is designed to degrade BRD4, enabling the selective proteolysis of PAC-1. The compound utilizes the chimeric BET degrader GNE-987, which is a highly potent degrader of BRD4, to exert its activity.
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| ln Vivo |
In vivo, PROTAC BRD4 degrader for PAC-1 is designed to be used as a tool for targeted protein degradation. By degrading BRD4, the conjugate enables the selective proteolysis of PAC-1 in animal models, providing a mechanism to study the biological function of PAC-1 in vivo. Preclinical studies have demonstrated its activity in this context.
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| Enzyme Assay |
PROTAC BRD4 degrader for PAC-1 is a complete molecule that consists of a PROTAC-linker conjugate. A cell-free binding assay is not typical for a full PROTAC as its mechanism requires the intracellular ubiquitin-proteasome system. The reported IC50 values for its constituent parts are likely derived from biochemical assays that measure the disruption of specific protein-protein interactions.
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| Cell Assay |
PROTAC BRD4 degrader for PAC-1 is designed to be used in cell-based assays. The compound is a PROTAC-linker conjugate. To assess its activity, cells are treated with the compound, and the degradation of PAC-1 or BRD4 is measured by Western blot. The effect on downstream signaling pathways and cell viability can also be assessed.
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| Animal Protocol |
A standard in vivo animal protocol for PROTAC BRD4 degrader for PAC-1 would involve mouse tumor xenograft models. Mice are injected with cancer cells expressing high levels of the target. Once tumors are established, mice are treated intravenously with the PROTAC-linker conjugate. Tumor size is measured regularly, and tissues are collected to measure target degradation by Western blot or IHC.
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| ADME/Pharmacokinetics |
The PROTAC BRD4 degrader for PAC-1 has a molecular weight of 1306.58 and the formula C62H77F2N9O12S4. It is a solid that should be stored at 4degC under nitrogen. Specific PK data are not available. As a PROTAC-linker conjugate for PAC, it is a specialized chemical tool with properties suited for advanced degradation studies.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for PROTAC BRD4 degrader for PAC-1 are not available. As a research chemical, standard laboratory safety precautions should be followed. Its safety profile is not documented for clinical use. The compound should be handled with care, using appropriate PPE in a well-ventilated area.
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| References |
[1]. Pillow TH, et al. Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity. ChemMedChem. 2019 Oct 31.
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| Additional Infomation |
PROTAC BRD4 degrader for PAC-1 is a research-grade chemical tool and is not approved for clinical use. It is a PROTAC-linker conjugate for PAC, comprising the chimeric BET degrader GNE-987 and a disulfide-containing linker. This compound is specifically designed to target and degrade BRD4, enabling selective proteolysis of PAC-1. It is used for advanced biochemical and cellular studies.
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| Molecular Formula |
C62H77F2N9O12S4
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|---|---|
| Exact Mass |
1305.454
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| PubChem CID |
145712388
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Rotatable Bond Count |
29
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| Heavy Atom Count |
89
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| Complexity |
2740
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNC(=O)C4=CC5=C(C=C4CS(=O)(=O)C)C6=CN(C(=O)C7=C6C(=CN7)CN5C8=C(C=C(C=N8)F)F)C)OC(=O)OCC(C)(C)SS(=O)(=O)C
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| InChi Key |
SCOQCGGMHFUNNF-FDTYQFAOSA-N
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| InChi Code |
InChI=1S/C62H77F2N9O12S4/c1-37-53(86-36-69-37)39-21-19-38(20-22-39)28-68-57(76)49-26-43(85-60(79)84-35-62(5,6)87-89(9,82)83)32-73(49)59(78)54(61(2,3)4)70-50(74)18-16-14-12-10-11-13-15-17-23-65-56(75)44-27-48-45(24-40(44)34-88(8,80)81)46-33-71(7)58(77)52-51(46)41(29-66-52)31-72(48)55-47(64)25-42(63)30-67-55/h19-22,24-25,27,29-30,33,36,43,49,54,66H,10-18,23,26,28,31-32,34-35H2,1-9H3,(H,65,75)(H,68,76)(H,70,74)/t43-,49+,54-/m1/s1
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| Chemical Name |
[(3R,5S)-1-[(2S)-2-[11-[[8-(3,5-difluoro-2-pyridinyl)-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carbonyl]amino]undecanoylamino]-3,3-dimethylbutanoyl]-5-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-3-yl] (2-methyl-2-methylsulfonylsulfanylpropyl) carbonate
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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 (~76.54 mM)
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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.) |
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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