PROTAC BTK/IKZF1/3 Degrader-1
PROTAC BTK/IKZF1/3 Degrader-1 is an orally active PROTAC-IMiD bifunctional protein degrader that selectively degrades BTK, IKZF1 and IKZF3. PROTAC BTK/IKZF1/3 Degrader-1 recruits the CRBN E3 ubiquitin ligase to form a ternary complex, mediating ubiquitination and proteasome-dependent degradation of target proteins, with no obvious degrading effect on GSPT1. PROTAC BTK/IKZF1/3 Degrader-1 inhibits cancer cell proliferation, induces cancer cell apoptosis, and suppresses tumor growth. PROTAC BTK/IKZF1/3 Degrader-1 can be used for the research of diffuse large B-cell lymphoma.
(Pink: Btk and IKZF1 and IKZF3 ligand (HY-179076); Blue: Cereblon ligand (HY-41547); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 2416130-49-7
- Formula: C43H51N11O6
- Molecular Weight:817.94
-
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]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
|
IKZF1 |
IKZF3 |
PROTAC BTK/IKZF1/3 Degrader-1 (BT6) (1 nM; 24 h) potently degrades BTK and IKZF1 in Mino cells[1].
PROTAC BTK/IKZF1/3 Degrader-1 (0.05-300 nM; 0.25-24 h) degrades BTK, IKZF1 and IKZF3 in OCI-ly10 cells in a concentration- and time-dependent manner, while exerting no significant degradation effect on GSPT1, thus exhibiting selective degradation activity[1].
PROTAC BTK/IKZF1/3 Degrader-1 induces BTK degradation in OCI-ly10 cells in a manner dependent on the formation of a ternary complex via the interaction between BTK and CRBN, and proceeds through the ubiquitin-proteasome pathway[1].
PROTAC BTK/IKZF1/3 Degrader‑1 shows that its anti‑proliferative activity against Jeko‑1 cells after 7‑day administration is dependent on CRBN expression, which confirms that its BTK degradation relies on the ubiquitin‑proteasome pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:Mino cells
-
Concentration:1 nM
-
Incubation Time:24 h
-
Result:Almost completely degraded BTK protein in Mino cells at 1 nM.
-
Cell Line:OCI-ly10 cells
-
Concentration:0.05, 0.14, 0.41, 1.23, 3.70, 11.1, 33.3, 100, 300 nM (concentration-dependent assay)
50 nM (time-dependent assay) -
Incubation Time:24 h (concentration-dependent assay)
0.25, 0.5, 1, 2, 3, 6, 12, 24 h (time-dependent assay) -
Result:Induced concentration-dependent degradation of BTK and IKZF1/3: BTK reached over 75% degradation at 33.3 nM, while IKZF1/3 levels began decreasing at 1.23 nM and reached over 50% degradation at 300 nM.
Induced time-dependent degradation: BTK was significantly reduced after 1 h of exposure to 50 nM, reaching over 70% degradation at 24 h; IKZF1/3 was significantly reduced after 6 h of exposure, reaching over 50% degradation at 24 h.
Did not exhibit significant degradation activity against GSPT1.
| Species | Dose | Route | Cmax | AUC0-t | AUC0-∞ | Tmax | T1/2 | Vd | CL | MRT |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 100 mg/kg | p.o. | 5662.71 ng/mL | 108822.08 ng/mL·h | 115039.06 ng/mL·h | 6 h | 11.03 h | 13.84 L/kg | 0.87 L/h/kg | 14.34 h |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD-SCID (female, 6 weeks old, subcutaneous xenograft with 5 × 106 OCI-ly1 cells)[1]
-
Dosage:3 mg/kg; 10 mg/kg
-
Administration:p.o.; daily; 21 days
-
Result:Induced tumor growth inhibition (TGI) of 95.54% at 3 mg/kg and 115.72% at 10 mg/kg.
Caused significant tumor regression at the 10 mg/kg dose.
Resulted in significant tumor weight reduction compared to the vehicle group and outperformed the positive control ibrutinib (10 mg/kg, TGI 61.26%).
Showed no significant changes in body weight across treatment groups.
Chemical Information
-
CAS No. 2416130-49-7
-
Molecular Weight 817.94
-
Formula C43H51N11O6
-
SMILES
CN1CCN(C1=O)[C@@H]2CCCN(C2)C3=CN=C(C(NC4=CC=C(C=C4)C5CCN(CC5)CC6CCN(C6)C7=CC8=C(C(N(C8=O)C9CCC(NC9=O)=O)=O)C=C7)=N3)C(N)=O
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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 BTK/IKZF1/3 Degrader-1 Related Classifications
HY-179077 Related Classifications
Powered by Bioz