protac parp1 degrader

PROTAC PARP1 degrader is a degrader of PARP1 based on the PROTAC technology. PROTAC PARP1 degrader at 10 μM at 24 h inhibits MDA-MB-231 cell line (IC50 of 6.12 μM).

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.

iRucaparib-AP6, a non-trapping PARP1 degrader, blocks both the catalytic activity and scaffolding effects of PARP1. iRucaparib-AP6 is a highly efficient and specific PARP1 degrader based on Rucaparib by using the PROTAC approach.

NH2-PEG7 is a para-aminomethylbenzyloxycarbonyl (PROTAC) linker compound consisting of a polyethylene glycol (PEG) chain. It finds application in the synthesis of the PROTAC PARP1 degrader called iRucaparib-AP6[1].

(S,R,S)-AHPC-C2-PEG4-N3 (VH032-C2-PEG4-N3) is a synthesized E3 ligase ligand-linker conjugate that combines the (S,R,S)-AHPC-based VHL ligand with a 4-unit polyethylene glycol (PEG) linker, used in PROteolysis TAgeting Chimera (PROTAC) technology. This compound aids in the formation of vRucaparib-TP4, a potent PARP1 degrader with a half-maximal degrading concentration (DC50) of 82 nM[1].

Thalidomide-NH-PEG7 is a synthesized conjugate of an E3 ligase ligand and linker, intended for use in antibody-drug conjugates (ADCs). It can be attached to a protein ligand via a linker to form PROTAC iRucaparib-AP6, a highly selective degrader of PARP1[1].

Thalidomide-piperidine-C-Pip-C2-Pip-C2-OH (Compound C6) is a conjugate linking a ligand and an E3 ligase, which is utilized in the synthesis of PROTAC PARP1 degrader-30.

CW-2 is a PARP1 PROTAC degrader known for its potent antiproliferative effects against MDA-MB-231 cells (IC50 = 0.72 μM) and cisplatin-resistant cells (A549/CDDP: IC50 = 3.52 μM). It exhibits synergistic antitumor activity and enhanced membrane permeability. CW-2 exerts its antitumor effects by inducing DNA damage, disrupting DNA repair, and triggering mitochondrial-dependent apoptosis (apoptosis).

Pomalidomide 4'-PEG3-azide is a chemically synthesized E3 ligase ligand-linker conjugate that incorporates the cereblon ligand derived from Pomalidomide, along with a linker. This compound is utilized in the synthesis of iRucaparib-TP3 (Compound 3), an effective PARP1 degrader developed through the PROTAC strategy and derived from Rucaparib.

Pomalidomide 5-piperidylamine serves as a conjugate of a linker and an E3 ligase ligand. This compound is utilized in the synthesis of PROTACPARP1 degrader-2.