PARP Degrader

IGF2BP1-IN-1, a Cucurbitacin B (HY-N0416) derivative, is a potent IGF2BP1 inhibitor (K_D = 2.88 nM). IGF2BP1-IN-1 binds directly to IGF2BP1, thereby inducing tumor cell cycle arrest, increasing apoptosis, and reducing autophagy. IGF2BP1-IN-1 can be used in research on NSLSC, colon, breast, liver, ovarian, pancreatic, and cervical cancers.

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

PARP1 PROTAC 180055 is a PARP1 PROTAC degrader that recruits VHL, with DC₅₀ values of 180 nM and 240 nM in T47D and MDA-MB-231 cells, respectively. PARP1 PROTAC 180055 selectively kills BRCA-mutant tumor cells by inducing PARP1 ubiquitination and proteasomal degradation, thereby blocking PARylation, NAD⁺ depletion and DNA trapping. PARP1 PROTAC 180055 can be used in the research of breast cancer, ovarian cancer, colorectal cancer, acute T-lymphoblastic leukemia, prostate cancer and osteosarcoma.

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.

PROTAC PARP1 degrader is a PROTAC PARP1 degrader. PROTAC PARP1 degrader mediates the interaction between PARP1 and MDM2 E3 ubiquitin ligase, thereby inducing ubiquitination of PARP1 and subsequent proteasome-mediated degradation. PROTAC PARP1 degrader selectively inhibits the growth of breast cancer cells. PROTAC PARP1 degrader induces cell apoptosis by activating caspase-3 and phosphatidylserine externalization. PROTAC PARP1 degrader can be used in the research of triple-negative breast cancer.

RBN012811 is a highly selective PROTAC-based PARP14 degrader. RBN012811 forms a ternary complex with cereblon by binding to the NAD⁺ site of PARP14, and mediates the specific degradation of PARP14 via the ubiquitin-proteasome pathway (IC₅₀=10 nM). RBN012811 effectively depletes endogenous PARP14 in various cell lines and primary human macrophages, thereby downregulating IL-10 production and IFN-β mRNA levels, increasing phosphorylated STAT1 levels to enhance inflammatory signaling, and inhibiting interferon-induced ADPr condensate formation. RBN012811 also modulates viral replication, exhibiting increased HSV1 replication while reducing VSV replication. RBN012811 has important application value in research related to cancer and viral infections.

rel-PROTAC PARP1 degrader is the relative configuration of ROTAC PARP1 degrader (HY-114324). PROTAC PARP1 degrader is a PROTAC PARP1 degrader. PROTAC PARP1 degrader mediates the interaction between PARP1 and MDM2 E3 ubiquitin ligase, thereby inducing ubiquitination of PARP1 and subsequent proteasome-mediated degradation. PROTAC PARP1 degrader selectively inhibits the growth of breast cancer cells. PROTAC PARP1 degrader induces cell apoptosis by activating caspase-3 and phosphatidylserine externalization. PROTAC PARP1 degrader can be used in the research of triple-negative breast cancer.

PROTAC PARP2 degrader-1 is an orally active PARP2 PROTAC degrader with a DC₅₀ of 2 μM. PROTAC PARP2 degrader-1 potently inhibits the enzymatic activities of PARP1 (IC₅₀ = 2.74 nM) and PARP2 (IC₅₀ = 0.32 nM), with approximately 10-fold higher selectivity for PARP2. PROTAC PARP2 degrader-1 induces cell cycle arrest and apoptosis, and exhibits significant anti-tumor efficacy in mouse models. PROTAC PARP2 degrader-1 can be used for the research of triple-negative breast cancer.

iVeliparib-AP6 is a proteolysis-targeting chimera (PROTAC) molecule designed based on Veliparib (HY-10129), which targets PARP1/2. The DC₅₀s of iVeliparib-AP6 for inducing the degradation of PARP1 and PARP2 are 36 nM and 63 nM, respectively, and its IC₅₀s are 69 nM and 21 nM, respectively. iVeliparib-AP6 contains a Veliparib-based PARP inhibitor warhead linked to a CRBN E3 ligase binder; it uses Thalidomide (HY-14658) as a ligand to recruit CRBN E3 ubiquitin ligase and exerts the PARP2 degradation mechanism.

DDO3602 is a PARP1 HSPTAC (HSP90-mediated proteolysis-targeting chimera) degrader, with a DC₅₀ of 490.3 nM against PARP1; its K_d values for PARP1 and HSP90 are 66.5 nM and 1.64 nM, respectively. DDO3602 induces the formation of an unnatural PARP1-HSP90 ternary complex, recruits E3 ubiquitin ligase, and promotes PARP1 degradation via the ubiquitin-proteasome pathway. DDO3602 induces G2/M cell cycle arrest, DNA damage, inhibits cell migration, and exhibits antiproliferative activity in breast cancer cells. DDO3602 can be used in breast cancer-related research.

2H-Indazole-7-carboxamide is a PARP1 ligand and can be used for the synthesis of PROTACs, such as PROTAC PARP1 degrader-1 (HY-158045).

iRucaparib-TP3 is a non-trapping PARP1 PROTAC degrader with concurrent PARP1 catalytic inhibitory activity. iRucaparib-TP3 induces PARP1 ubiquitination and subsequent proteasomal degradation. iRucaparib-TP3 can be used for the research of cervical adenocarcinoma.

PROTAC PARP1 degrader-2 (Compound 72) is a PROTAC degrader for PARP with a DC₅₀<10 nM in MDA-MB-231 cell. PROTAC PARP1 degrader-2 inhibits the cell viability of MDA-MB-436 with an IC₅₀ <100 nM.

Antitumor agent-214 is a chalcone analogue with anti-tumor activity. Antitumor agent-214 induces cell cycle arrest and apoptosis in tumor cells, disrupts mitochondrial metabolism, and upregulates the expression of caspase 3, caspase 7 and caspase 9, downregulates PARP1. Antitumor agent-214 can be used for anti-tumor research related to colorectal cancer, breast cancer, lung cancer, and cervical cancer.

Thalidomide-piperidine-C-Pip-C2-Pip-C2-OH (Compound C6) is a conjugate of the linker and E3 ligase ligand, that can be used in synthesis of PROTAC PARP1 degrader-30 (HY-168722).

Vrucaparib-TP4 (Compound 9) is a PARP1 PROTAC-type degrader. Vrucaparib-TP4 promotes the ubiquitination and degradation of PARP1. Vrucaparib-TP4 can be used in the research of tumors.

CW-2 is a CRBN-recruited PARP1 PROTAC degrader. CW-2 triggers multiple downstream biological effects including DNA damage accumulation, impaired DNA repair, mitochondrial-mediated apoptosis, intracellular ROS buildup and G1/S cell cycle arrest, as well as the regulation of oxidative phosphorylation, p53, PI3K-Akt and MAPK alongside ubiquitin proteolysis pathways. CW-2 enhances cell membrane permeability and intracellular platinum enrichment, exhibits detectable pharmacokinetic profiles after intraperitoneal administration in rats and drives differential gene expression. CW-2 can be applied to research on triple-negative breast cancer, non-small cell lung cancer, cisplatin-resistant non-small cell lung cancer, colon cancer and pancreatic cancer.

PROTAC PARP1 degrader-5 is a PARP1 PROTAC degrader with a DC₅₀ of 0.12 μM. PROTAC PARP1 degrader-5 hijacks the ubiquitin-proteasome system via catalytic ternary complex formation to drive sustained PARP1 degradation. PROTAC PARP1 degrader-5 induces DNA damage, drives marginal cytosolic double-stranded DNA accumulation in tumor cells, and up-regulates PD-L1 surface expression in tumor cells. PROTAC PARP1 degrader-5 shows tumor growth inhibition activity in murine melanoma models when encapsulated in lipid nanoparticles. PROTAC PARP1 degrader-5 can be used for the research of cancer, such as melanoma.

PARP1 degrader 1 (Compound 2c) is a comparatively potent PARP1 HyT degrader (DC₅₀: 618 nM for intracellular PARP-1). PARP1 degrader 1 is also a HyT-Olaparib (HY-10162) conjugate. PARP1 degrader 1 induces UPR/autophagy, thus facilitating the degradation of PARP-1. PARP1 Degrader 1 can be used in the research of cancer.

PARP1 degrader-2 (Compound 11e) is a potent, selective PARP1 HYT degrader (DC₅₀: 2.16 μM). PARP1 degrader-2 selectively binds to and degrades PARP1 but not PARP2. PARP1 degrader-2 mediates the degradation of PARP1 via the ubiquitin-proteasome system (UPS). PARP1 degrader-2 exhibits anticancer activity against triple-negative breast cancer and colon cancer (hydrophobic tag: (HY-W022007); PARP1 ligand: (HY-75706); Linker: (HY-W015300)).