PROTAC FGFR2 degrader 1
PROTAC FGFR2 degrader 1 (compound N5) is a PROTAC that effectively targets FGFR2 with DC50 of 6.46 nM, the FGFR2 IC50 is 0.08 nM. PROTAC FGFR2 degrader 1 has anti-proliferative activity and highly selective, induces G0/G1 arrest of KATOIII and SNU16 cell cycle and inhibits apoptosis by reducing the activation of p-ERK and p-PLCγ, the downstream proteins of FGFR2. PROTAC FGFR2 degrader 1 potently inhibits the growth of SNU16 xenograft tumors in mouse model.
(Pink: FGFR2 ligand (HY-18708); Blue: Cereblon ligand (HY-10984); Black: linker (HY-163989)).
For research use only. We do not sell to patients.
- CAS No.: 3099123-99-3
- Formula: C46H54N10O7
- Molecular Weight:858.98
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Storage:Powder -20°C, 3 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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- References
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Help & FAQs
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Biological Activity
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FGFR2 |
PROTAC FGFR2 degrader 1 (0-1000 nM, 72 h) IC50 is less than 0.17 nM for both Kato III and SNU16[1].< br/> PROTAC FGFR2 degrader 1 (500 nM; 12 h; WB) induces FGFR2 degradation in Kato III, which is highly selective for FGFR2 and UPS-dependent[1].< br/> PROTAC FGFR2 degrader 1 (500, 1000 nM; 24 h) induces cell cycle arrest of Kato III and SNU16 cells in G0/G1 phase[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KATO III, SNU16
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Concentration:0, 0.1, 1, 10, 100, 500, 1000 nM
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Incubation Time:0, 1, 6, 12, 24, 36 h
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Result:Degraded FGFR2 in Kato III cells with timedependent. Induced FGFR2 degradation in SNU16 cells in vivo in a mouse model. Decreased CDK2, CDK 4, Cyclin D1 and Cyclin E.
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Cell Line:KATO III, SNU16
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Concentration:500 nM, 12 h; Pomalidomide (10 μM), Erdafitinib (10 μM), MG132 (5 μM) for 6 h; 50, 100, 500 nM for 24 h
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Incubation Time:12 h; 24 h
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Result:Degraded FGFR2 via the UPS pathway, and degradation of FGFR2 was dependent on the formation of the FGFR2-N5-E3 ligase complex and subsequent proteasomal degradation. Showed that phosphorylation of p-AKT was decreased in both SNU16 and Kato III cells, inhibited the activation of p-ERK and p-PLC γ effectively.
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Cell Line:KATO III
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Concentration:500 nM
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Incubation Time:12 h
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Result:Degraded FGFR2 in KATOIII with high selectivity.
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Cell Line:KATO III, SNU16
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Concentration:500, 1000 nM
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Incubation Time:24 h
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Result:Showed that the percentage of KATO III cells in the G0/G1 phase increased from 47.7% to 67.1% in the 1000 nM of PROTAC FGFR2 degrader 1, the number of SNU16 cells increased from 45.9% to 67.5%.
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Cell Line:KATO III, SNU16
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Concentration:1000 nM
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Incubation Time:24 h
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Result:Showed that the apoptosis rate of KATO III cells increased from 10.9% in the DMSO group to 30.5%, upregulation of cleaved caspase 3 was observed.
Pharmacokinetic profiles of PROTAC FGFR2 degrader 1 in SD rats.[1]
| Parameters | PROTAC FGFR2 degrader 1 2mg/kg(i.v.) | Parameters | PROTAC FGFR2 degrader 1 2mg/kg(i.p.) |
| t1/2 (h) | 4.65±4.14 | t1/2 (h) | 7.59±0.365 |
| Tmax (h) | / | Tmax (h) | 0.25±0.177 |
| Cmax (ng/mL) | / | Cmax (ng/mL) | 302±33.7 |
| MRTinf (h) | 2.27±1.44 | MRTinf (h) | 6.53±0.0721 |
| CL (mL/min/kg) | 59.3±8.35 | CL/F (mL/min/kg) | 78.2±1.62 |
| Vss (L/kg) | 7.58±3.80 | VZ/F (L/kg) | 51.4±2.40 |
| AUC0-t (h*ng/mL) | 544±74.2 | AUC0-t (h*ng/mL) | 991±20.7 |
| AUC0-inf (h*ng/mL) | 570±83.3 | AUC0-inf (h*ng/mL) | 1066±21.9 |
| AUC0-t/ AUC0-inf | 0.956±0.0232 | AUC0-t/ AUC0-inf | 0.930±0.00429 |
| F | / | F (%) | 74.8±1.53 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SD rats[1]
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Dosage:2, 5 mg/kg
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Administration:Intravenous injection (i.v.); Intraperitoneal injection (i.p.)
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Result:Absorbed rapidly in vivo, reached its maximum concentration at 0.25 h by 5 mg/kg, and then slowly cleared from the body, with a half-life of 7.59 h.
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Animal Model:A mouse model of subcutaneous xenograft of SNU16 tumor[1]
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Dosage:10, 20 mg/kg
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Administration:Intraperitoneal injection(i.p.); once daily; 25 days
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Result:Showed the stronger anti-tumor effect, greater tumor growth inhibition and a significant reduction in tumor weight.
Chemical Information
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CAS No. 3099123-99-3
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Appearance Solid
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Molecular Weight 858.98
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Formula C46H54N10O7
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Color Light yellow to yellow
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SMILES
COC1=CC(OC)=CC(N(C2=CC=C3N=CC(C4=CN(N=C4)CCCCCCC(NCCNC5=C6C(N(C(C6=CC=C5)=O)C7CCC(NC7=O)=O)=O)=O)=NC3=C2)CCNC(C)C)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Purity & Documentation
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Data Sheet (277 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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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC FGFR2 degrader 1 Related Classifications
HY-163985 Related Classifications
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