dIRF4-2
Based on 1 Customer Validation
dIRF4-2 is a selective IRF4 PROTAC degrader with a DC50 value of 2.2 μM. dIRF4-2 forms a ternary complex between IRF4 and CRBN, inducing ubiquitination and proteasomal degradation of IRF4. dIRF4-2 downregulates MYC. dIRF4-2 exhibits anticancer activity against myeloma. dIRF4-2 acts as a chemical probe for investigating IRF4 function, mimicking the IRF4 gene knockout phenotype. dIRF4-2 can be used in the research of multiple myeloma.
(Pink: IRF4 ligand (HY-185698); Blue: Cereblon ligand (HY-14658); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.11%
- No. CAS: 3136609-62-3
- Fòrmula: C43H46N8O7
- Peso molecular:786.87
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Almacenamiento:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
In Vitro
dIRF4-2 (1-20 μM; 24 h) induces dose-dependent proteasomal degradation of IRF4 in MM1.S and OPM2 multiple myeloma cell lines, with DC50 values of 2.2 μM and 2.3 μM respectively after 24 h of treatment[1].
dIRF4-2 (2.5 μM; 2-10 h) induces rapid and sustained degradation of IRF4 (initiated within 2 h), and treatment with 2.5 μM for up to 10 h does not affect the off-target novel substrate IKZF3 in MM1.S and OPM2 multiple myeloma cell lines[1].
dIRF4-2 (2.5 μM; 2 h) induces the degradation of IRF4 in MM1.S multiple myeloma cells, and this degradation process is proteasome-dependent; co-treatment with 1 μM bortezomib or 1 μM MG132 followed by a 2-hour incubation restores IRF4 levels[1].
dIRF4-2 (2.5 μM; 4 h) induces highly selective degradation of IRF4 in MM1.S multiple myeloma cells, and exerts no significant effects on other IRF family members or novel CRBN substrates after 4 h of treatment at 2.5 μM[1].
dIRF4-2 (100 μM three-fold dilution series; 96 h, with second dose at 48 h) induces potent, IRF4-dependent cytotoxicity in all tested multiple myeloma cell lines after 96 h of treatment (IC50 0.68-8 μM), while exerting no effect on IRF4-independent HEK293T cells (IC50 > 50 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MM1.S, OPM2
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Concentration:1, 2.5, 5, 10, 20 μM
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Incubation Time:24 h
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Result:Induced dose-dependent degradation of IRF4 in both MM1.S and OPM2 cell lines.
Reached half-maximal degradation concentration (DC50) of 2.2 μM for MM1.S and 2.3 μM for OPM2.
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Cell Line:MM1.S, OPM2
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Concentration:2.5 μM
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Incubation Time:2, 4, 6, 8, 10 h
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Result:Induced rapid depletion of IRF4 within 2 hours, with sustained degradation through 10 hours.
Showed no degradation of the off-target neosubstrate IKZF3 at any timepoint.
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Cell Line:12 human multiple myeloma cell lines, HEK293T
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Concentration:100 μM three-fold dilution series
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Incubation Time:96 h (with second dose at 48 h)
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Result:Exhibited IRF4-dependent cytotoxicity across all multiple myeloma cell lines tested, with IC50 values ranging from 0.68 μM (Karpas-707) to 8 μM (MOLP-2).
Showed no cytotoxicity in non-IRF4-dependent HEK293T cell line, with an IC50 > 50 μM.
Chemical Information
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No. CAS 3136609-62-3
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Appearance Solid
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Peso molecular 786.87
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Fòrmula C43H46N8O7
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Color Light yellow to yellow
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SMILES
COC1=CC=C(C2(CC2)C(N[C@H](C(NC)=O)C3=CC=CC(C4=CN(CCCN5CCN(C6=CC=C(C(N(C7C(NC(CC7)=O)=O)C8=O)=O)C8=C6)CC5)N=C4)=C3)=O)C=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (127.09 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.18 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocolo
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Gene Editing
Gene editing modify specific sites within the genome through gene deletions, insertions or conversions to study functionally unknown genes or conduct gene therapy. It is also used to change the biological traits of organisms to establish new varieties. Gene editing techniques include zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas 9) (CRISPR/Cas9).
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CRISPR-Cas9 knockout in cultured mammalian cells
CRISPR-Cas9 knockout in cultured mammalian cells uses an sgRNA to direct Cas9 to a complementary genomic sequence adjacent to a compatible PAM; Cas9 creates a targeted DNA double-strand break, and repair by non-homologous end joining can introduce insertions or deletions that disrupt the coding sequence or functional genomic element. The readout of knockout is detection of edited alleles and loss of gene product or phenotype, commonly by PCR/Sanger-sequence trace decomposition, targeted sequencing, immunoblotting, immunostaining, or flow cytometry when the target protein is detectable at the cell surface.
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CRISPR-Cas9 zebrafish embryo editing
CRISPR-Cas9 zebrafish embryo editing introduces targeted double-strand breaks in genomic DNA by delivering Cas9 nuclease with a guide RNA into one-cell-stage embryos; repair by endogenous DNA-repair pathways produces indels or donor-mediated insertions that can be detected by phenotype, PCR-based genotyping, heteroduplex assays, Sanger sequencing, or amplicon sequencing. The readout reflects the frequency and spectrum of edited alleles in mosaic F0 embryos or transmitted F1 animals; because injected embryos can carry multiple alleles, founder screening and sequence confirmation are required before establishing stable mutant lines.
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Constitutive Germline Knockout Model
Constitutive germline knockout models are generated by producing a heritable loss-of-function allele in the mouse genome, typically through complete gene disruption in embryonic stem (ES) cells followed by germline transmission or through CRISPR/Cas-mediated editing of zygotes, resulting in offspring that carry a stable null allele in all tissues. Classical approaches rely on homologous recombination in ES cells to introduce targeted gene disruptions, which are then transmitted through chimeric mice to the germline. More recent genome editing strategies use CRISPR/Cas systems to induce double-strand breaks and non-homologous end joining (NHEJ), frequently generating frameshift mutations that abolish gene function, enabling faster generation of knockout alleles directly in embryos. Germline transmission or direct germline editing ensures that the mutation is present in all cells of the resulting animal, allowing systemic functional analysis of gene loss.
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CRISPR/Cas9 Knockout Animal Model
CRISPR/Cas9 knockout animal modeling uses guide RNA to direct Cas9 to a genomic target, where Cas9 creates a DNA double-strand break; repair by error-prone non-homologous end joining generates insertions or deletions that can disrupt coding sequence and produce knockout alleles. Classic animal-model workflows deliver Cas9 mRNA or Cas9 protein with sgRNA into fertilized zygotes by microinjection or electroporation, then transfer edited embryos into pseudopregnant recipients and genotype founders for target-site mutations.
Pureza y Documentación
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Ficha de datos (273 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.2709 mL | 6.3543 mL | 12.7086 mL | 31.7714 mL |
| 5 mM | 0.2542 mL | 1.2709 mL | 2.5417 mL | 6.3543 mL | |
| 10 mM | 0.1271 mL | 0.6354 mL | 1.2709 mL | 3.1771 mL | |
| 15 mM | 0.0847 mL | 0.4236 mL | 0.8472 mL | 2.1181 mL | |
| 20 mM | 0.0635 mL | 0.3177 mL | 0.6354 mL | 1.5886 mL | |
| 25 mM | 0.0508 mL | 0.2542 mL | 0.5083 mL | 1.2709 mL | |
| 30 mM | 0.0424 mL | 0.2118 mL | 0.4236 mL | 1.0590 mL | |
| 40 mM | 0.0318 mL | 0.1589 mL | 0.3177 mL | 0.7943 mL | |
| 50 mM | 0.0254 mL | 0.1271 mL | 0.2542 mL | 0.6354 mL | |
| 60 mM | 0.0212 mL | 0.1059 mL | 0.2118 mL | 0.5295 mL | |
| 80 mM | 0.0159 mL | 0.0794 mL | 0.1589 mL | 0.3971 mL | |
| 100 mM | 0.0127 mL | 0.0635 mL | 0.1271 mL | 0.3177 mL |
dIRF4-2 Related Classifications
HY-185697 Related Classifications
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