YB-3-17
YB-3-17 is a blood-brain barrier permeable mTOR inhibitor (IC50 = 0.22 nM) and GSPT1 PROTAC degrader. YB-3-17 inhibits mTORC1/2, CK1δ/ε, mutant ALK and HER2 kinases, induces CRBN-dependent selective GSPT1 degradation, ablates mTOR downstream phosphorylation, downregulates c-Myc/Cyclin D1 to impair tumor translation, triggers p53-mediated apoptosis, suppresses tumor proliferation and xenograft tumor growth, and can be used for the study of glioma, neuroblastoma, breast cancer, lymphoma, colorectal cancer and lung cancer.
(Pink: GSPT1 ligand (HY-170407); Blue: Cereblon ligand (HY-14658); Black: linker (HY-A0102)).
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- CAS. Nr.: 2940242-88-4
- Formel: C38H39N11O6
- Molecular Weight:745.79
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Speicherung:
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
IC50: 0.22 nM (mTOR)
DC50: 5 nM (GSPT1)
YB-3-17 (1 μM) potently and selectively inhibits mTOR, mTORC1, CK1δ, CK1ε, ALKC1156Y, HER2, and HER4 in a cell-free kinome profiling assay[1].
YB-3-17 (10 serial threefold dilutions starting from 200 μM; 10 min preincubation, 30 min substrate incubation) inhibits purified mTOR enzyme activity in a cell-free Caliper Mobility shift assay[1].
YB-3-17 (300 nM; 4 h) alters protein abundance in U87 glioblastoma cells[1].
YB-3-17 (300 nM; 8 h, 24 h) alters gene expression in U251 glioblastoma cells[1].
YB-3-17 (1-3 μM; 12 h) induces CRBN-dependent degradation of GSPT1 and reduces pS6K levels in wild-type HeLa cells, with no GSPT1-degrading activity in CRBN-knockout HeLa cells[1].
YB-3-17 (0.3-1 μM; 12 h) reduces levels of GSPT1, c-Myc, CyclinD1, pS6K, and p4EBP1 in a concentration-dependent manner in U87 glioblastoma cells, without altering mTOR complex component levels[1].
YB-3-17 (10 μM; 3 h) induces the formation of a CRBN-GSPT1-mTOR complex in Flag-CRBN-expressing HeLa cells[1].
YB-3-17 (1-300 nM; 2-12 h) time- and concentration-dependently inhibits mTORC1/mTORC2 signaling and degrades GSPT1 via a CRBN- and proteasome-dependent mechanism in U87 glioblastoma cells, with a GSPT1 DC50 of 5 nM[1].
YB-3-17 (0.01-10000 nM; 72 h) potently inhibits the proliferation of U87, U251, SK-N-SH, T98G, U118, and SHSY-5Y tumor cells with IC50 values as low as 3.3 nM[1].
YB-3-17 (300 nM, 0.1-3 μM; 4 h) selectively degrades GSPT1 without altering GSPT2, SNUPN, or other proteins in U87 glioblastoma cells[1].
YB-3-17 (8 h) modulates gene expression in U251 glioblastoma cells, enriching pathways related to apoptosis, p53 signaling, and mTOR inhibition, and upregulating genes that enhance mTOR inhibitory activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:wild-type HeLa cells, CRBN-knockout HeLa cells
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Concentration:1, 3 μM
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Incubation Time:12 h
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Result:Reduced GSPT1 protein levels in a concentration-dependent manner and reduced pS6K levels in wild-type HeLa cells.
Did not reduce GSPT1 levels and had a diminished effect on pS6K levels in CRBN-knockout HeLa cells.
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Cell Line:U87 glioblastoma cells
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Concentration:0.3, 1 μM
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Incubation Time:12 h
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Result:Reduced GSPT1, c-Myc, CyclinD1, pS6K, and p4EBP1 protein levels in a concentration-dependent manner.
Left mTOR, Rictor, Raptor, Sin1, and GβL levels unchanged.
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Cell Line:U87 glioblastoma cells
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Concentration:1, 3, 10, 30, 100 nM (12 h); 300 nM (2, 4, 6, 8, 12 h); 300 nM (4 h)
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Incubation Time:12 h (1-100 nM); 2, 4, 6, 8, 12 h (300 nM); 4 h (300 nM)
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Result:Induced time- and concentration-dependent inhibition of mTORC1 and mTORC2 signaling, as shown by reduced phosphorylation of S6K, 4EBP1, and AKT.
Initiated downstream mTOR inhibition at concentrations as low as 10 nM.
Efficiently degraded GSPT1, with substantial degradation observed within 6 h at 300 nM, and a half-maximal degradation concentration (DC50) of 5 nM.
Achieved near-complete GSPT1 degradation at 10 nM after 12 h.
Reduced cyclin D1 expression.
GSPT1 degradation was blocked by proteasome inhibitors, neddylation inhibitors, and Pomalidomide (HY-10984).
Did not degrade mTOR complex components (Raptor, Rictor).
YB-3−17 (2.5-20 mg/kg; i.p.; once daily for 18 days with 1-day breaks) exhibits high in vivo glioblastoma xenograft efficacy and safety, with 10 mg/kg and 20 mg/kg doses driving near-complete tumor growth arrest and regression while maintaining mouse health[1].
YB-3-17 demonstrates measurable distribution to plasma and brain in healthy C57BL/6 mice, with a brain/plasma ratio of 1.01% at 5 mg/mL (i.v.; single dose) and 1.25% at 10 mg/kg (i.p.; single dose)[1].
YB-3−17 (10-30 mg/kg; i.p.; daily for 3 days) demonstrates a in vivo safety profile in healthy nu/nu-nude mice, with 10 mg/kg and 30 mg/kg doses supporting 100% survival and stable body weight[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:nu/nu-nude mice (6-week-old female, subcutaneous glioblastoma xenograft via 5×106 U87 cells in 50 v/v Matrigel/MEM)[1]
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Dosage:5, 10, 20 mg/kg
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Administration:i.p.; once daily for 3 days
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Result:Reduced GSPT1, CyclinD1, and pS6K protein levels in tumor tissues relative to vehicle controls.
Increased pAKT levels in tumor tissues relative to vehicle controls.
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Animal Model:nu/nu-nude (male; glioblastoma xenograft via U87 cell inoculation)[1]
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Dosage:2.5, 5, 10, 20 mg/kg
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Administration:i.p.; once daily for 18 days with 1-day breaks
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Result:Produced tumor inhibition.
Nearly completely halted tumor growth, leading to tumor regression at 10 mg/kg and 20 mg/kg.
Maintained good health with only minor weight loss at 20 mg/kg.
Dose-dependently degraded GSPT1 and inhibited phosphorylation of mTOR downstream proteins (pAKT, pS6K) and reduced cyclin D1 levels in tumor tissue.
Achieved great reduction of GSPT1, pAKT, pS6K, and cyclin D1 at 10 mg/kg and 20 mg/kg.
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Animal Model:nu/nu-nude[1]
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Dosage:10, 30 mg/kg
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Administration:i.p.; once daily for 3 days
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Result:Maintained 100% survival at 10 mg/kg and 30 mg/kg.
Showed no significant weight loss over the 3-day period at 10 mg/kg and 30 mg/kg.
Chemical Information
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CAS. Nr. 2940242-88-4
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Molecular Weight 745.79
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Formel C38H39N11O6
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SMILES
NC(O1)=NC2=C1C=CC(C3=NN(C4CCN(C(C5CCC(CNC6=CC=C(C(N(C7C(NC(CC7)=O)=O)C8=O)=O)C8=C6)CC5)=O)CC4)C9=NC=NC(N)=C93)=C2
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
YB-3-17 Related Classifications
HY-170405 Related Classifications
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