COT-01
COT-01 is a CRBN-dependent Cyclin D2 Molecular glue degrader with an IC50 of 2.5 μM for CRBN. COT-01 does not change CCND2 mRNA levels. COT-01 induces G0/G1 phase arrest and Apoptosis. COT-01 exhibits anticancer activity against multiple myeloma.
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- CAS. Nr.: 447458-15-3
- Formel: C37H44N2O9
- Molecular Weight:660.75
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Speicherung:
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
CRBN 2.5 μM (IC50) |
In Vitro
COT-01 increases the level of cleaved caspase-3 in multiple myeloma cells[1].
COT-01 does not significantly change CCND2 mRNA in multiple myeloma cells, supporting a post-translational reduction of Cyclin D2[1].
COT-01 (2.5-10 μM; 24 h) restores G0/G1 phase arrest in MM.1S and RPMI 8226 cells, while having minimal effect on U266B1 cells[1].
Baseline Cyclin D2 expression is lower in U266B1 cells than in MM.1S cells[1].
COT-01-induced Cyclin D2 degradation in MM.1S cells is attenuated by OUN20985 depletion of CRBN[1].
COT-01-induced Cyclin D2 degradation in MM.1S cells requires cullin-RING E3 ligase and proteasome activity[1].
COT-01 (10 μM; 15-30 min) promotes CRBN-Cyclin D2 binding in MM.1S cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MM.1S, RPMI 8226, and U266B1 multiple myeloma cells
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Concentration:2.5, 5, 7.5, 10 μM
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Incubation Time:120 h
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Result:Significantly reduced MM.1S and RPMI 8226 viability in a dose-dependent manner; U266B1 remained largely insensitive across most concentrations, with only a marginal decline at 10 μM.
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Cell Line:MM.1S, RPMI 8226, and U266B1 multiple myeloma cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:48 h
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Result:Increased apoptotic populations dose-dependently; at 10 μM, apoptosis reached approximately 40% in MM.1S and 30% in RPMI 8226; U266B1 showed minimal apoptosis at the same concentration.
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Cell Line:MM.1S, RPMI 8226, and U266B1 cells
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Concentration:2.5, 5, and 10 μM
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Incubation Time:24 h
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Result:In MM.1S, G0/G1 was 77% under starvation, 54% in complete medium, and 57%, 62%, and 77% at 2.5, 5, and 10 μM, respectively.
In RPMI 8226, G0/G1 was 76% under starvation, 50% in complete medium, and 51%, 58%, and 74% at 2.5, 5, and 10 μM.
U266B1 showed minimal changes, with G0/G1 reaching 47% at 10 μM.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB17-SCID (male, 7 weeks old)[1]
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Dosage:30 mg/kg; 100 mg/kg
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Administration:i.p.; daily; from average tumor volume ~100 mm3 until vehicle group reached ~1500 mm3
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Result:Produced dose-dependent tumor growth inhibition.
The 30 mg/kg dose caused a moderate reduction in tumor volume, while 100 mg/kg suppressed tumor progression compared with vehicle.
Final tumor weight was reduced in the 100 mg/kg group.
Tumor growth inhibition was 21.5% at 30 mg/kg and 58.8% at 100 mg/kg.
In tumor tissue from the 100 mg/kg group, Cyclin D2 was markedly reduced, CRBN was unchanged, and cleaved caspase-3 was substantially increased.
Chemical Information
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CAS. Nr. 447458-15-3
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Molecular Weight 660.75
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Formel C37H44N2O9
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SMILES
O[C@]1(C(COC(CCC(N[C@@H](CC2=CNC3=C2C=CC=C3)C(OC)=O)=O)=O)=O)CC[C@@]([C@]1(C)C4)([H])[C@@]5([H])[C@]([C@](CC6)(C)C(CC5)=CC6=O)([H])C4=O
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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)
COT-01 Related Classifications
HY-190708 Related Classifications
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