DN1679
DN1679 is a potent, selective and orally active CRBN-dependent CDK12/13 PROTAC dual degrader. DN1679 shows DC50 of 8.8/9.8 nM (MDA-MB-231), 5.1/6.4 nM (MDA-MB-157) and 17.2/15.8 nM (MDA-MB-468) for CDK12/13. DN1679 can downregulate DNA damage response gene mRNA levels, such as ATM, ATR, BRCA1 and RAD51. DN1679 demonstrates a potent synergistic anti-tumor effect companied with Olaparib (HY-10162). DN1679 can be used for research of triple-negative breast cance.
(Pink: CDK12 and CDK13 ligand (HY-181036); Blue: Cereblon ligand (HY-W093272); Black: linker).
For research use only. We do not sell to patients.
- Formula: C52H53F4N11O8S
- Molecular Weight:1068.10
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
CDK12 8.8 nM (DC50) |
CDK13 9.8 nM (DC50) |
Cereblon |
In Vitro
DN1679 inhibits MDA-MB-231, MDA-MB-157 and MDA-MB-468 cells proliferation with IC50 values of 31.7, 49.1 and 121.4 nM. DN1679 has low cytotoxicity to normal human cell lines (MCF10A and NCM460) (IC50 of 236.9 and 378.5 nM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | T1/2 | AUC0-t | CL |
|---|---|---|---|---|---|---|---|
| Mice[1] | 20 mg/kg | p.o. | 2.0 h | 3617 ng/mL | 4.1 h | 15730 ng·h/mL | 1309 mL/h/kg |
Chemical Information
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Molecular Weight 1068.10
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Formula C52H53F4N11O8S
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SMILES
CC(N([C@@H]1CC[C@H](CC1)NC2=NC(C3=CN=CC(S(C)(=O)=O)=C3)=C(C=N2)C(F)(F)F)C4=CC=C(C=C4)C5=CN=C(N=C5)O[C@H]6CN(CC6)CC7CCN(CC7)C8=CC(C(N9C%10CCC(NC%10=O)=O)=O)=C(C=C8F)C9=O)=O
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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.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)