BSJ-4-116

SKU: orb1218280

Description

BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM. It downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation).

Key Properties

• CAS Number: 2519823-34-6
• MW: 837.38
• Purity: >98% (HPLC)
• Formula: C₄₀H₄₉ClN₈O₈S
• SMILES: O=C(NCCCCCCCN1C[C@H](NC2=NC=C(Cl)C(NC3=CC=CC=C3S(=O)(C(C)C)=O)=N2)CCC1)COC4=CC=CC(C(N5C(CC6)C(NC6=O)=O)=O)=C4C5=O
• Target: CDK
• Solubility: DMSO:250 mg/mL (298.55 mM; Need ultrasonic)

Bioactivity

• In Vitro:
  BSJ-4-116 (10-10000 nM; 72 hours) exhibits potent antiproliferative effects in Kelly CDK12C1039F. BSJ-4-116 (50 nM; 6-24 hours) decreases the level of CDK12 protein, regardless of the mutational status of the cell line. BSJ-4-116 inhibits the growth of T-ALL cells (Jurkat and MOLT-4 cells) and sensitizes them to PARP inhibition. BSJ-4-116 regulates DDR genes via poly(adenylation). BSJ-4-116 overcomes CDK12C1039F mutation. BSJ-4-116 represents the first example of resistance to a bivalent degrader molecule that is a consequence of an acquired point mutation in the target protein. Cell Proliferation Assay Cell line: Parental Kelly and CDK12C1039F cells. Concentration: 10-10000 nM. Incubation time: 72 hours. Result: Antiproliferative activity of BSJ-4-116 is independent of the mutational status, and the degrader compounds exhibited improved GR50 (growth rate inhibition) values in Kelly CDK12C1039F cells compared with the parental cell line. Western blot analysis. Cell line: Parental and CDK12C1039F (KellyCDK12CF)-expressing Kelly cells. Concentration: 50 nM. Incubation time: 6-24 hours. Result: Led to the same level of CDK12 protein level decrease, regardless of the mutational status of the cell line.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

CDK