pcna

PCNA-I1 is an inhibitor targeting PCNA chromatin association in prostate cancer.

AOH1996 belongs to small molecule inhibitors and is a PCNA ligand targeting transcription-replication conflicts, with oral activity, metabolic stability, and tumor selectivity. This compound induces transcription-dependent DNA double-strand breaks and apoptosis, and is used for antitumor therapy.

AOH1160 is an inhibitor of proliferating cell nuclear antigen (PCNA). AOH1160 induces apoptosis and causes cell-cycle arrest by interfering with DNA replication.

(S)-10-Hydroxycamptothecin (10-HCPT) is a DNA topoisomerase I inhibitor used as a clinical therapeutic agent against hepatoma.

T2AA (4-[4-[(2S)-2-amino-3-hydroxypropyl]-2,6-diiodophenoxy]phenol) is an inhibitor of proliferating cell nuclear antigen (PCNA) with IC50 of 1 μM for PCNA/PIP-box peptide interaction. T2AA suppresses cancer cell growth and causes DNA replication stress by stalling DNA replication forks and inhibiting PCNA interaction with DNA polymerase δ.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

PCNA-IN-1 (Compound 11) is an inhibitor of the PCNA/PIP-box interaction, with an IC50 greater than 50 μM. It is applicable in cancer research.

Ganodermanontriol is a purified triterpene extracted from GL that inhibits proliferation of HCT-116 and HT-29 colon cancer cells without significantly compromising cell viability and suppresses β-catenin transcriptional activity and cyclin D1 protein levels in a dose-dependent manner. Ganodermanontriol also reduces Cdk-4 and PCNA while increasing E-cadherin and β-catenin accumulation in HT-29 cells, Ganodermanontriol markedly suppresses tumor growth in an HT-29 xenograft mouse model without adverse effects, highlighting its strong potential as a chemotherapeutic candidate for colorectal cancer research.

ML323 is a reversible and effective USP1-UAF1 inhibitor in a Ub-Rho assay (IC50: 76 nM) and in orthogonal gel-based assays using K63-linked diubiquitin (di-Ub) (IC50: 174 nM 820 nM)and monoubiquitinated PCNA (Ub-PCNA) (IC50: 820 nM) as substrates, respectively.

Antitumor agent-163 (Compound 3) serves as a photosensitizer in molecular-targeted photodynamic therapy (MT-PDT) aimed at carbonic anhydrase IX (CAIX). Under illumination at 540 nm, Antitumor agent-163 inactivates CAIX protein through singlet oxygen generation without affecting internal standard proteins such as α-tubulin, β-actin, and proliferating cell nuclear antigen (PCNA). It induces cell membrane damage and reduces cell viability with IC50 values of 0.2 μM for A549 and 0.05 μM for U87MG. Furthermore, Antitumor agent-163 demonstrates antitumor activity in mouse models.

LOXL2/sGC modulator-2 (Compound 9k) is a selective, orally active dual-target modulator of lysyl oxidase-like protein 2 (LOXL2) and soluble guanylate cyclase (sGC). It inhibits LOXL2 with an IC50 of 0.1 μM and acts as an sGC activator. This compound can improve vascular remodeling and reduce pulmonary arterial pressure while downregulating PKG1, PCNA, α-SMA, collagen I, and fibronectin levels. LOXL2/sGC modulator-2 is useful for studying pulmonary arterial hypertension.

USP1-IN-15 is an orally effective and selective inhibitor of USP1 with an IC50 of 12.3 nM. It demonstrates high specificity towards USP1, with negligible inhibition of off-target deubiquitinating enzymes. USP1-IN-15 blocks cell colony formation, induces S phase arrest, and stabilizes ubiquitinated PCNA. Additionally, USP1-IN-15 exhibits synergistic antiproliferative activity and significantly inhibits tumor growth in vivo. This compound can be utilized for research on BRCA-mutated breast cancer.

Linuron, a substituted phenylurea herbicide, primarily functions by disrupting the photosynthetic process through the inhibition of photosystem II. it additionally acts as an androgen receptor antagonist, exhibiting endocrine-disrupting effects and reproductive toxicity, Maternal linuron exposure alters testicular development in male offspring at the whole genome level and significantly altering expressions of key testosterone synthesis-associated genes including Star, P450scc, 3β-Hsd, Abp, Cox7a2, Pcna, p450c17, and 17β-Hsd.

I-138 is an orally active and potent reversible inhibitor of USP1-UAF1.I-138 induces mono-ubiquitination of FANCD2 and PCNA and inhibits USP1 auto-cleavage in cells.

PEP1 acetate is a p21-mimetic peptide that serves as a specific proliferating cell nuclear antigen (PCNA) binding inhibitor. It arrests the cell cycle in the S phase by competitively blocking the interaction between PCNA and DNA polymerase delta, thereby interfering with DNA replication.

T2AA, a proliferating cell nuclear antigen (PCNA) inhibitor, disrupts protein-protein interactions between PCNA and both a PIP-box-containing peptide (IC50= 1 μM) and full-length p21, reducing cellular colocalization of PCNA with DNA polymerase δ. This compound effectively inhibits DNA replication and cell proliferation in U2OS and HeLa cells in a concentration-dependent manner, additionally inducing S phase cell cycle arrest at a 20 μM concentration. Furthermore, T2AA enhances DNA double strand break formation alongside cisplatin in a neutral comet assay and augments cisplatin-induced reductions in clonogenic survival in HeLa and U2OS cells.

TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models.

13C-D3-AOH1996 is the 13C and deuterated compound of AOH1996. 13C-AOH1996 (T77520) has a CAS number of 2089314-64-5. AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC).AOH1996 interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis.AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II.AOH1996 acts synergistically with DNA damaging agents to inhibit tumor cell growth. AOH1996 inhibits tumor cell growth by stabilizing the interaction between PCNA and RNA polymerase II, leading to proteasome-dependent rpb1 degradation and lethal DNA damage.AOH1996 acts synergistically with DNA damaging agents.

AOH-D3 is a deuterated compound of AOH. AOH (T77520) has a CAS number of 2089314-64-5. AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC).AOH1996 interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis.AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II.AOH1996 acts synergistically with DNA damaging agents to inhibit tumor cell growth. AOH1996 inhibits tumor cell growth by stabilizing the interaction between PCNA and RNA polymerase II, leading to proteasome-dependent rpb1 degradation and lethal DNA damage.AOH1996 acts synergistically with DNA damaging agents.

p21PBP, a peptide composed of 20 amino acids, serves as an inhibitor of DNA replication. It specifically binds to the purified proliferating cell nuclear antigen (PCNA) found in extracts from tumor cells. p21PBP holds potential for use in cancer research.