YW-N-7 TFA
YW-N-7 TFA is a PROTAC degrader targeting RET kinase, with an IC50 of 8.4 nM. YW-N-7 TFA inhibits RET kinase activity and induces proteasome-mediated degradation of RET fusion proteins, while enhancing the anti-tumor activity of Selpercatinib (LOXO-292) (HY-114370). YW-N-7 TFA can be used in the research of cancers associated with RET gene abnormalities, including medullary thyroid carcinoma, papillary thyroid carcinoma and non-small cell lung cancer.
(Pink: RET ligand (HY-170856); Blue: Cereblon E3 ligase ligand; Black: linker (HY-W086181)).
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- Fòrmula: C58H63F3N12O9
- Peso molecular:1129.19
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
RET 8.4 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| TPC1 | IC50 |
8.4 nM
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Inhibition of RET autokinase activity in human TPC1 thyroid carcinoma cells assessed by reduced phosphorylated RET (pRET Y905) levels via immunoblotting after 24 h treatment.
Inhibition of RET autokinase activity in human TPC1 thyroid carcinoma cells assessed by reduced phosphorylated RET (pRET Y905) levels via immunoblotting after 24 h treatment.
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39723919 |
| TPC1 | IC50 |
26.4 nM
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Degradation of CCDC6-RET protein in human TPC1 thyroid carcinoma cells assessed by protein level analysis via immunoblotting after 24 h treatment.
Degradation of CCDC6-RET protein in human TPC1 thyroid carcinoma cells assessed by protein level analysis via immunoblotting after 24 h treatment.
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39723919 |
In Vitro
YW-N-7 (200 nM; 24 h) TFA exhibits high specificity for RET in human TPC1 thyroid cancer cells[1].
YW-N-7 (0.1-500 nM; treated for 3 days in BaF3 cell line, treated for 5 hours in IMR-90 cells) TFA selectively inhibits the viability of BaF3/KIF5B-RET cells, but shows no activity against IL-3-dependent BaF3 cells, VEGFR2-dependent BaF3/TEL-VEGFR2 cells, or normal IMR-90 human diploid fibroblasts[1].
YW-N-7 (50-250 nM; 15 h) TFA inhibits RET kinase activity and degrades KIF5B-RET protein in BaF3/KIF5B-RET cells[1].
YW-N-7 (0.1-500 nM; 3 days) TFA potently inhibits the proliferation of BaF3/KIF5B-RET cells[1].
YW-N-7 (200 nM; 24 h) TFA significantly reduces RET protein abundance in CCDC6-RET fusion-positive TPC1 thyroid cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human TPC1 thyroid carcinoma cells (CCDC6-RET fusion-positive)
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Concentration:0.5, 1, 5, 10, 25, 50, 100 nM (24 h); 50, 250 nM (3, 6, 9, 24, 48 h)
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Incubation Time:3, 6, 9, 24, 48 h
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Result:Inhibited RET kinase activity and degraded CCDC6-RET protein in a dose-dependent manner.
Reduced CCDC6-RET protein with a half-life of 2 h at 50 nM, reaching a maximal 97.3% reduction at 9 h, and maintaining 93.5% reduction at 24 h.
Reduced CCDC6-RET protein with a half-life of 5 h at 250 nM, with a maximal 88% reduction at 9 h.
Prevented CCDC6-RET degradation but retained kinase inhibition when cotreated with excess LOXO-292 or lenalidomide.
Blocked CCDC6-RET degradation but still inhibited kinase activity when cotreated with bortezomib.
Exhibited an IC50 of 8.4 nM for RET autokinase inhibition and an IC50 of 26.4 nM for CCDC6-RET degradation.
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Cell Line:BaF3/KIF5B-RET (B/KR) cells
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Concentration:50, 100, 250 nM
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Incubation Time:15 h
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Result:Inhibited RET kinase activity (reduced pRET Y905 levels) in a dose-dependent manner.
Degraded KIF5B-RET protein in a dose-dependent manner.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SHO (female, 6-week-old)[1]
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Dosage:100 mg/kg; 150 mg/kg
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Administration:i.p.; once daily (Day 9 start for 100 mg/kg; Day 17 start for 150 mg/kg)
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Result:Significantly inhibited tumor growth compared to vehicle control.
Reduced tumor size at study end point compared to vehicle control.
Decreased levels of active Tyr-905-phosphorylated KIF5B-RET and total KIF5B-RET protein in tumor samples.
Did not reduce animal body weight at either dose.
Chemical Information
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Peso molecular 1129.19
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Fòrmula C58H63F3N12O9
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SMILES
O=C(C1=CN=C(C=C1)N2CCN(CC2)C(CCCCCCCOC3=CN4C(C(C5=CC=C(N=C5)N6CC7CC(C6)N7CC8=CC=C(N=C8)OC)=C3)=C(C=N4)C#N)=O)NCCOC9=CC=C(C=C9)C(C(N%10)=O)CCC%10=O.O=C(O)C(F)(F)F
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
YW-N-7 TFA Related Classifications
HY-170855A Related Classifications
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