PROTAC CDK2-pRb degrader-1
PROTAC CDK2-pRb degrader-1 is an orally active PROTAC-class degrader of CDK2. PROTAC CDK2-pRb degrader-1 effectively inhibits the phosphorylation of retinoblastoma protein (Rb) at serine residues 807/811 by inducing ubiquitination and proteasomal degradation of CDK2. PROTAC CDK2-pRb degrader-1 exhibits significant activity against human cells (with EC50 values of 12 nM and 125 nM, respectively). In xenograft models, PROTAC CDK2-pRb degrader-1 effectively inhibits tumor growth and induces tumor stasis, making it suitable for research related to CCNE1-amplified cancers (such as ovarian cancer, gastric cancer, and breast cancer).
For research use only. We do not sell to patients.
- CAS No.: 3030276-48-0
- Formula: C40H50F4N8O5S
- Molecular Weight:830.93
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
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CDK2/cyclinE |
PROTAC CDK2-pRb degrader-1 (Compound 5) (dose-response concentrations; 24 h) co-degrades CDK2 and cyclin E1 with enhanced activity in CCNE1-amplified human cancer cell lines and restores RB pathway inhibition in albociclib (HY-50767)-adapted breast cancer cells with cyclin E1 overexpression[1].
PROTAC CDK2-pRb degrader-1 (dose-response concentrations; 7 days) exhibits antiproliferative activity in MKN1 and HCC1569 human cancer cell lines that is dependent on CRBN[1].
PROTAC CDK2-pRb degrader-1 (dose-response concentrations; 7 days) exhibits antiproliferative activity in HCC1569 human breast cancer cells that is strictly dependent on functional RB protein[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MKN1 (CRBNwt, CRBNKO), HCC1569 (CRBNwt, CRBNKO)
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Concentration:dose-response concentrations
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Incubation Time:7 days
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Result:Lost antiproliferative activity in CRBNKO MKN1 and HCC1569 cells, with proliferation largely restored compared to CRBNwt cells where the degrader potently suppressed growth.
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Cell Line:HCC1569 (RBwt, RBKO)
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Concentration:dose-response concentrations
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Incubation Time:7 days
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Result:Showed >300-fold reduced antiproliferative potency in RBKO HCC1569 cells compared to RBwt cells.
PROTAC CDK2-pRb degrader-1 (50 mg/kg; p.o.; twice daily) induces tumor stasis or regression; it achieves 90% CDK2 degradation and pRB inhibition in the CCNE1-amplified HCC1569 breast cancer xenograft model[1].
PROTAC CDK2-pRb degrader-1 (50 mg/kg; p.o.; once daily) induces tumor stasis or regression; it achieves 90% CDK2 degradation and pRB inhibition in the CCNE1-amplified MKN1 gastric cancer xenograft model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD SCID (female)[1]
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Dosage:50 mg/kg
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Administration:p.o.; BID
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Result:Inhibited nearly 90% of phosphorylated Rb (pRB) in tumor tissue, with decreased rebound of pRB signal at trough compared to PF-07104091 (HY-137894A).
Induced potent tumor growth inhibition (TGI) of 85%.
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Animal Model:NOG (female)[1]
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Dosage:15 mg/kg; 30 mg/kg; 50 mg/kg
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Administration:p.o.; BID
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Result:Achieved sustained 90% CDK2 degradation and 90% pRB inhibition in tumor tissue at 30 and 50 mg/kg BID.
Induced tumor stasis with 95% TGI at 30 mg/kg compared to vehicle.
Induced 5% tumor regression at 50 mg/kg compared to vehicle.
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Animal Model:BALB/c Nude (female)[1]
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Dosage:30 mg/kg; 50 mg/kg
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Administration:p.o.; QD
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Result:Induced 90% CDK2 degradation and 90% pRB inhibition in tumor tissue at 50 mg/kg QD.
Induced tumor stasis (TGI=97%) at 30 mg/kg compared to vehicle.
Induced 47% tumor regression at 50 mg/kg compared to vehicle.
Chemical Information
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CAS No. 3030276-48-0
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Molecular Weight 830.93
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Formula C40H50F4N8O5S
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SMILES
FC(F)(C1=CN=C(NC2=C(C=C(C=C2)S(N[C@H]3CC[C@@H](CC3)CN4CCN(C5=C(C=C(C6C(NC(CC6)=O)=O)C=C5)F)CC4)(=O)=O)C)N=C1N7C[C@@](O)(CCC7)C)F
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Shipping
Room temperature in continental US; may vary elsewhere.
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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 CDK2-pRb degrader-1 Related Classifications
HY-186132 Related Classifications
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