Zomiradomide
Based on 1 Customer Validation
Zomiradomide (KT-413) is an orally active IRAK4 PROTAC degrader with a DC50 of 6 nM. Zomiradomide inhibits the NF-κB signaling pathway, while its molecular glue function mediates the degradation of Ikaros and Aiolos (with a DC50 of 1 nM for both), activates the IFN-I signaling pathway, and selectively degrades IMiD substrates. Zomiradomide inhibits cancer cell proliferation and tumor growth. Zomiradomide can be used in research related to B-cell non-Hodgkin's lymphoma and diffuse large B-cell lymphoma.
(Pink: IRAK4 ligand (HY-168311); Blue: Cereblon ligand (HY-W039116); Black: linker (HY-168313)).
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- Purity: 98.04%
- CAS No.: 2655656-99-6
- 화학식: C45H48F3N7O6S
- 분자량:871.97
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
All PROTACs Isoforms
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Biological Activity
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IRAK4 6 nM (DC50) |
Ikaros 1 nM (DC50) |
Aiolos 1 nM (DC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| OCI-Ly10 | IC50 |
11 nM
Compound: 32
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Antiproliferative activity against human OCI-Ly10 cells measured after 4 days by CellTiter-Glo Luminescent Cell Viability Assay
Antiproliferative activity against human OCI-Ly10 cells measured after 4 days by CellTiter-Glo Luminescent Cell Viability Assay
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[PMID: 38920289] |
Zomiradomide (1-41 nM; 0-24 h) potently degrades IRAK4 (DC50 = 6 nM), Ikaros (DC50 = 1 nM) and Aiolos (DC50 = 1 nM) in OCI-Ly10 cells, with faster degradation kinetics for Ikaros and Aiolos than for IRAK4[2].
Zomiradomide (60 nM; 2-8 h) selectively degrades IRAK4 and IMiD substrates (Ikaros, Aiolos, ZFP91, WIZ), induces type I interferon responses, and exerts no effect on GSPT1 in OCI-Ly10 cells when treated at 60 nM for 2 h and 8 h[2].
Zomiradomide (for 4 days) potently inhibits the viability of OCI-Ly10 cells, with an IC50 of 11 nM[2].
Zomiradomide (1 μM) exhibits high selectivity against the human kinome, with an S10 score of 0.005 at 1 μM[2].
Zomiradomide exhibits favorable in vitro DMPK properties, including low intrinsic clearance in human liver microsomes and hepatocytes, high plasma protein binding, and moderate passive permeability[2].
Zomiradomide (100 nM; 24 h) selectively degrades IRAK4 and known IMiD substrates (Ikaros, Aiolos, ZFP276, ZFP91, WIZ) in unstimulated human peripheral blood mononuclear cells (PBMC), with no effect on the pan-essential substrate GSPT1[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Clearance (CL) | Vss | T1/2 | AUC | F |
|---|---|---|---|---|---|---|---|
| Mice[2] | 2 mg/kg | i.v. | 11 mL/min/kg | 7.5 L/kg | 8.6 h | / | / |
| Mice[2] | 10 mg/kg | p.o. | / | / | / | 2.8 μM·h | 19 % |
| Rat[2] | 2 mg/kg | i.v. | 9.1 mL/min/kg | 15 L/kg | 17 h | / | / |
| Rat[2] | 10 mg/kg | p.o. | / | / | / | 2.7 μM·h | 15 h |
| Dog[2] | 0.2 mg/kg | i.v. | 14 mL/min/kg | 29 L/kg | 28 h | / | / |
| Dog[2] | 2.1 mg/kg | p.o. | / | / | / | 0.46 μM·h | 21 % |
Zomiradomide (20 mg/kg; p.o.; 3 days of administration followed by 5 days of withdrawal) induces complete tumor regression in MYD88- and CD79-mutated diffuse large B-cell lymphoma patient-derived xenograft models in NPG mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female CB-17.SCID mice aged 6-8 weeks are implanted subcutaneously in the right flank with 10 × 106 OCI-Ly10 human B-cell non-Hodgkin lymphoma cells (harboring the MYD88 L265P activating mutation) suspended in 0.2 mL of a 1:1 mixture of PBS and Matrigel (Corning)[2]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 38 days
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Result:Induced tumor growth regression at all doses.
Achieved complete tumor responses in animals treated with 10 mg/kg and 30 mg/kg doses.
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Animal Model:NPG mice are implanted subcutaneously with tumor fragments derived from a patient-derived xenograft (PDX) model of diffuse large B-cell lymphoma (DLBCL) designated LY14019, which harbors both MYD88 L265P and CD79 comutations. The tumor is serially passaged in NPG mice and maintained as frozen stocks for subsequent implantation[2]
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Dosage:20 mg/kg
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Administration:p.o.; 3 days on, 5 days off
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Result:Achieved complete tumor regression with the intermittent dosing regimen.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2655656-99-6
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Appearance Solid
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분자량 871.97
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화학식 C45H48F3N7O6S
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Color Light yellow to yellow
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SMILES
O=C(N1C2C(NC(CC2)=O)=O)C3=CC=CC(NCCC(C4)CC4(C5)CN5C[C@H]6CC[C@H](C(SC7=C8)=NC7=CC(C(C)(O)C)=C8NC(C9=CC=CC(C(F)(F)F)=N9)=O)CC6)=C3C1=O
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Synonyms
KT-413
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 100 mg/mL (114.68 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. 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. 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)
순도&문서
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Data Sheet (275 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
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. 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1468 mL | 5.7341 mL | 11.4683 mL | 28.6707 mL |
| 5 mM | 0.2294 mL | 1.1468 mL | 2.2937 mL | 5.7341 mL | |
| 10 mM | 0.1147 mL | 0.5734 mL | 1.1468 mL | 2.8671 mL | |
| 15 mM | 0.0765 mL | 0.3823 mL | 0.7646 mL | 1.9114 mL | |
| 20 mM | 0.0573 mL | 0.2867 mL | 0.5734 mL | 1.4335 mL | |
| 25 mM | 0.0459 mL | 0.2294 mL | 0.4587 mL | 1.1468 mL | |
| 30 mM | 0.0382 mL | 0.1911 mL | 0.3823 mL | 0.9557 mL | |
| 40 mM | 0.0287 mL | 0.1434 mL | 0.2867 mL | 0.7168 mL | |
| 50 mM | 0.0229 mL | 0.1147 mL | 0.2294 mL | 0.5734 mL | |
| 60 mM | 0.0191 mL | 0.0956 mL | 0.1911 mL | 0.4778 mL | |
| 80 mM | 0.0143 mL | 0.0717 mL | 0.1434 mL | 0.3584 mL | |
| 100 mM | 0.0115 mL | 0.0573 mL | 0.1147 mL | 0.2867 mL |
Zomiradomide Related Classifications
HY-153368 Related Classifications
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