protac parp-1 degrader

PROTAC PARP1 degrader is a targeted protein degrader of PARP1 developed using PROTAC technology, and at 10 μM for 24 hours inhibits the proliferation of the MDA-MB-231 breast cancer cell line with an IC50 of 6.12 μM, providing a powerful research tool for studying DNA damage response, PARP1 biology, and degradation-based cancer therapeutics.

PROTAC PARP1 degrader-3 (Compound C6) is a PROTAC degrader specifically targeting PARP1, with a DC50 of 58.14 nM. It demonstrates cytotoxicity in SW-620 and LOVO cancer cells, with IC50 values of 1.63 μM and 2.84 μM, respectively. In BRCA-mutated colon cancer cells, PROTAC PARP1 degrader-3 exhibits synergistic effects with SN-38, with a combination index (CI) of 0.487.

PROTAC PARP1 degrader-4 (Compound 180055) is a selective PARP1 PROTAC degrader, demonstrating DC50 values of 180 nM and 240 nM in T47D and MDA-MB-231 cell lines, respectively. It facilitates the ubiquitination and degradation of PARP1 and inhibits its enzymatic activity without causing significant DNA trapping effects. Additionally, PROTAC PARP1 degrader-4 can inhibit tumors with BRCA gene mutations while having minimal impact on the growth of normal cells.

PROTACPARP1 degrader-1 (Compound CN0) serves as a PROTAC degrader of PARP1. It activates the cGAS/STING immune pathway, ultimately enhancing T cell-mediated tumor cell killing. PROTACPARP1 degrader-1 inhibits DNA damage repair, leading to the efficient accumulation of cytoplasmic DNA fragments.

PROTACPARP1 degrader-2 (Compound 72) is a potent PROTAC degrader of PARP, achieving a DC50 of less than 10 nM in MDA-MB-231 cells. Additionally, this compound effectively inhibits the viability of MDA-MB-436 cells with an IC50 of less than 100 nM.

PROTACROR1degrader-1 (Compound 11d) serves as a PROTAC degrader targeting the pseudokinase ROR1, with the capability of degrading ROR1 in NSCLC cells at a DC50 of 40-80 nM. It induces PARP cleavage and apoptosis in NCI-H23 cells. [Pink: ligand for target protein ROR1 ligand-1; Black: linker; Blue: ligand for VHL E3 ligase (S,R,S)-AHPC]

PP-C8, a potent and selective PROTAC CDK12-Cyclin K degrader, efficiently induces degradation of CDK12 and Cyclin K, with DC50 values of 416 nM and 412 nM, respectively. This compound exhibits significant synergistic antiproliferative effects when combined with a PARP inhibitor in triple-negative breast cancer (TNBC) [1].

JNJ-1013 is a potent and selective IRAK1 degrader, with IC50 values of 72 nM for IRAK1, 443 nM for IRAK4, and 1071 nM for VHL FP. It induces apoptosis, increases cleaved PARP expression, and decreases the expression of IRAK1, p-IKBα, and pSTAT3(Tyr705) [1].