PROTAC PARP1 degrader-1 

PROTAC PARP1 degrader-1 is a PARP1 PROTAC degrader with a DC₅₀ value of 252.5 nM. PROTAC PARP1 degrader-1, combined with Daunorubicin (HY-13062A), induces the accumulation of cytoplasmic DNA fragments, activates the cGAS/STING innate immune pathway, and remodels the tumor microenvironment. PROTAC PARP1 degrader-1 can be used in research related to breast cancer^[1]. (Pink: PARP-1 ligand (HY-W973851); Blue: Cereblon ligand (HY-41547); Black: linker).

PROTAC PARP1 degrader-1 (CN0) (10 μM; 24 h) does not induce DNA damage alone, but cotreatment with Daunorubicin inhibits DNA repair in MDA-MB-231 breast cancer cells, leading to significant accumulation of DNA double-strand breaks and cytosolic dsDNA^[1].
PROTAC PARP1 degrader-1 (CN0) (10 μM) alone does not significantly inhibit cell growth, but cotreatment with Daunorubicin synergistically inhibits growth of MDA-MB-231 and 4T1 breast cancer cells (CI < 1) without affecting untransformed MCF-10A breast epithelial cells^[1].
PROTAC PARP1 degrader-1 (CN0) (10 μM; 24 h) alone does not activate the cGAS/STING pathway, but cotreatment with Daunorubicin significantly activates the cGAS/STING innate immune pathway in MDA-MB-231 breast cancer cells, increasing key phosphoprotein levels and proinflammatory cytokine/chemokine gene expression^[1].
PROTAC PARP1 degrader-1 (CN0) (10 μM; 24 h pretreatment) alone enhances T cell-mediated killing of MDA-MB-231 breast cancer cells, and cotreatment with Daunorubicin significantly increases this killing effect^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PROTAC PARP1 degrader-1 (Compound CN0) (25 mg/kg; i.p.; daily for 4 days, then daily on days 15-18) effectively degrades PARP1 in tumor tissue, while combined with Daunorubicin produces potent antitumor activity in a 4T1 breast cancer allograft model via enhanced CD8-positive T cell infiltration, with no significant body weight loss^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

576.60

C₃₂H₂₈N₆O₅

3032324-56-1

Solid

Light yellow to yellow

NC(C1=CC=CC2=CN(N=C21)C3=CC=C(C=C3)C4CN(CCC4)C5=C(C6=CC=C5)C(N(C6=O)C7CCC(NC7=O)=O)=O)=O

Room temperature in continental US; may vary elsewhere.

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Lin S, et al. Discovery of CN0 as a novel proteolysis-targeting chimera (PROTAC) degrader of PARP1 that can activate the cGAS/STING immunity pathway combined with daunorubicin. Bioorg Med Chem. 2022;70:116912.  [Content Brief]