PROTAC IRAK4 degrader-12
PROTAC IRAK4 degrader-12 is an orally active IRAK4 PROTAC degrader with a DC50 of 4.87 nM in K562 IRAK4-HiBiT cells. PROTAC IRAK4 degrader-12 induces protein degradation of IRAK4, IKZF1 and IKZF3. It inhibits the proliferation of diffuse large B-cell lymphoma cells. It suppresses tumor growth in mouse xenograft models of lymphoma cells. PROTAC IRAK4 degrader-12 can be used for the research of B-cell lymphoma and diffuse large B-cell lymphoma.
(Pink: IRAK4 ligand (HY-168611); Blue: Cereblon ligand (HY-W733885); Black: linker (HY-75005)).
For research use only. We do not sell to patients.
- CAS No.: 2919995-09-6
- Formula: C46H50ClF2N11O6
- Molecular Weight:926.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
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- References
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Biological Activity
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IRAK4 |
IKZF1 |
IKZF3 |
PROTAC IRAK4 degrader-12 (hydrochloride salt of I) (10 mM stock, 3-fold serial dilutions; 16-18 h) potently degrades IRAK4 protein in K562 IRAK4-HiBiT cells, with a DC50 of 4.87 nM and a maximum degradation rate of 108.46%[1].
PROTAC IRAK4 degrader-12 (starting concentration of 300 nM, 3-fold serial dilutions; 24 h) degrades IKZF1 and IKZF3 proteins in MM.1S cells, with DC50 values of 23.40 nM and 20.64 nM, and maximum degradation rates of 72.32% and 73.46%, respectively[1].
PROTAC IRAK4 degrader-12 (5 days) potently inhibits the proliferation of OCI-LY10 and TMD-8 lymphoma cells, with IC50 values of 13.66 nM and 10.34 nM, and maximum inhibition rates of 94.54% and 89.86%, respectively[1].
PROTAC IRAK4 degrader-12 (for 4 days) potently inhibits the proliferation of SU-DHL-2 lymphoma cells, with an IC50 of 28.70 nM and a maximum inhibition rate of 93.55%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PROTAC IRAK4 degrader-12 (10-100 mg/kg; p.o.; once daily; for 21 consecutive days) exhibits significant anti-tumor activity in a CB17 SCID mouse xenograft model of SU-DHL-2 lymphoma, with a TGI of 72.07% at the 100 mg/kg dose[1].
PROTAC IRAK4 degrader-12 (10-100 mg/kg; p.o.; once daily; for 22 consecutive days) exhibits significant dose-dependent anti-tumor activity in the BALB/c nude mouse xenograft model of TMD-8 diffuse large B-cell lymphoma, with a TGI of 88% at the dose of 100 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID (female, 6-8 weeks old, 17-20 g, human OCI-LY10 B-cell lymphoma xenograft)[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Achieved an average tumor volume of 685.61 mm3, relative tumor volume of 3.37, T/C ratio of 47.40%, and TGI of 60.43% at 10 mg/kg on Day 28.
Achieved an average tumor volume of 322.68 mm3, relative tumor volume of 1.64, T/C ratio of 23.07%, and TGI of 89.94% at 30 mg/kg on Day 28.
Achieved an average tumor volume of 188.01 mm3, relative tumor volume of 0.91, T/C ratio of 12.80%, and TGI of 100.96% at 100 mg/kg on Day 28.
Showed statistically significant differences compared to the vehicle control (p < 0.003) in all treatment groups.
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Animal Model:CB17 SCID (female, 6-8 weeks old, 18-22 g, human SU-DHL-2 lymphoma xenograft)[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Achieved an average tumor volume of 800 mm3, relative tumor volume of 5.79, T/C ratio of 42.33%, and TGI of 62.13% at 10 mg/kg on Day 21.
Achieved an average tumor volume of 813 mm3, relative tumor volume of 5.78, T/C ratio of 42.26%, and TGI of 61.41% at 30 mg/kg on Day 21.
Achieved an average tumor volume of 626 mm3, relative tumor volume of 4.55, T/C ratio of 33.23%, and TGI of 72.07% at 100 mg/kg on Day 21.
Showed statistically significant differences compared to the vehicle control (p < 0.001) in all treatment groups.
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Animal Model:BALB/c nude (female, 6-8 weeks old, human TMD-8 diffuse large B-cell lymphoma xenograft)[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 22 days
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Result:Achieved an average tumor volume of 714 mm3, relative tumor volume of 4.41, T/C ratio of 58%, and TGI of 49% at 10 mg/kg on Day 22, with statistically significant difference compared to the vehicle control (p < 0.05).
Achieved an average tumor volume of 430 mm3, relative tumor volume of 2.60, T/C ratio of 34%, and TGI of 75% at 30 mg/kg on Day 22, with statistically significant difference compared to the vehicle control (p < 0.01).
Achieved an average tumor volume of 291 mm3, relative tumor volume of 1.78, T/C ratio of 23%, and TGI of 88% at 100 mg/kg on Day 22, with statistically significant difference compared to the vehicle control (p < 0.01).
Chemical Information
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CAS No. 2919995-09-6
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Molecular Weight 926.41
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Formula C46H50ClF2N11O6
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SMILES
O=C1CCC(C(N1)=O)C2=NOC3=C2C4=C(C(NC(CN5CCN(CC5)C[C@@H]6CC[C@H](CC6)N7C=C(C(C(F)F)=N7)NC(C8=COC(C9=CC(NCC%10CC%10)=NC=C9)=N8)=O)=O)=CC=C4)C=C3.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC IRAK4 degrader-12 Related Classifications
HY-168586 Related Classifications
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