PARP

PARP-2/1-IN-2 (Compound 4a), the enantiomer of Veliparib (HY-10129), is a potent PARP inhibitor with K_is of 2 and 5 nM against PARP-2 and PARP-1, respectively. PARP-2/1-IN-2 has an EC₅₀ of 3 nM in a cell based assay of PARP activity.

PARP1-IN-28 (compound 1) is a PARP1 inhibitor. PARP1-IN-28 can be used in the study of cancer.

PARP7-IN-25 is a PARP7 inhibitor with an IC₅₀ of 1.582 nM.PARP7-IN-25 inhibits enzymatic activity of PARP7. PARP7-IN-25 inhibits proliferation of lung cancer cells.PARP7-IN-25 can be used for the research of PARP7-related cancer.

Cajanol is an isoflavanone that can be isolated from the roots of Cajanus cajan (L.) Millsp.. Cajanol inhibits cancer cell proliferation and induces cancer cell apoptosis. Cajanol promotes the expression of Bax, inhibits the expression of Bcl-2, activates caspase-9 and caspase-3, induces PARP cleavage, arrests the cell cycle at the G2/M phase, generates ROS, disrupts mitochondrial membrane potential and triggers cytochrome c release. Cajanol induces bacterial DNA damage, disrupts bacterial cell membranes, and exerts antibacterial activity in vitro. Cajanol reduces the expression of PI3K, inhibits the phosphorylation of Akt and NF-κB, downregulates the expression and transport function of P-gp, restores the sensitivity of drug-resistant cancer cells to Paclitaxel, and inhibits the growth of Paclitaxel-resistant metastatic ovarian tumors. Cajanol is applicable to research related to breast cancer, ovarian cancer and bacterial infections.

Anticancer agent 201 (Compound 2f) has IC₅₀ values in the low micromolar range for multiple tumor cell lines. Anticancer agent 201 is highly cytotoxic to CCRF-CEM cells in vitro, inducing apotosis by activating caspase-3 in the intrinsic mitochondrial pathway and lysis of PARP, as well as reducing the expression of Bcl-2 and Bcl-XL proteins. Anticancer agent 201 can be used in cancer research.

PARP1/NAMPT-IN-1 is a potent and dual PARP1 and NAMPT inhibitor with IC₅₀ values of 1.2 nM and 6.7 nM, respectively. PARP1/NAMPT-IN-1 can disrupt the homologous recombination repair (HRR) pathway, leading to the accumulation of DNA double-strand breaks (DSBs), inducing cell cycle arrest and apoptosis, and also has antimigratory effects. PARP1/NAMPT-IN-1 exhibits excellent antitumor effects in a breast cancer xenograft model. PARP1/NAMPT-IN-1 can be used for the study of triple-negative breast cancer (TNBC).

PARP1/BRD4-IN-3 (compound HF4) is a potent BRD4 and PARP1 inhibitor with IC₅₀ values of 1210, 2019 nM for BRD4, PARP1, respectively. PARP1/BRD4-IN-3 shows antiproliferative activities. PARP1/BRD4-IN-3 induces apoptosis and cell cycle arrest at G0/G1 phase. PARP1/BRD4-IN-3 causes DNA damage and reduces the protein expression of Rad51. PARP1/BRD4-IN-3 shows antitumor efficacy.

PARP-1/Proteasome-IN-1 (compound 42i) is a dual PARP-1 and proteasome inhibitor with significant inhibitory effects on breast cancer. PARP-1/Proteasome-IN-1 can downregulate the expression of BRCA1 and RAD51 to inhibit homologous recombination repair function and induce apoptosis.

CHNQD-00824 is a Terphenyllin (HY-119821) derivative with potent anticancer effect. CHNQD-00824 inhibits the proliferation and migration of cancer cells via DNA damage. CHNQD-00824 triggers apoptosis and inhibits Doxycin Hydrochloride (DOX)-induced liver-specific enlargement in zebrafish embryos. CHNQD-00824 can be used for cancer research, such as liver and breast cancer.

HDAC-IN-91 is a multiple inhibitor of HDAC (IC₅₀ = 134.22 nM for HDAC1, 66.29 nM for HDAC2), carbonic anhydrase (CA) (K_i = 72.03 nM for CA IX, 50.76 nM for XII), and tubulin polymerization ( IC₅₀ = 2.56 μM). HDAC-IN-91 inhibits PARP1 and increases the Bax/Bcl-2 ratio. HDAC-IN-91 blocks the cell cycle at the G2/M phase and induces apoptosis through a mitochondrial apoptosis activation mechanism. HDAC-IN-91 can exert potent cytotoxic activity through tubulin polymerization inhibition. HDAC-IN-91 can be used in breast, colorectal, cervical and lung cancer research.

PARP1/2-IN-4 (compound 3) is a PARP1/2 inhibitor.

OUL245 is a 7-Hydroxy derivative, and a selectively PARP2 inhibitor (IC₅₀=44 nM). OUL245 also inhibits other PARP and TNKS enzymes with IC₅₀s of 2.9-8.8 μM.

TH5427 hydrochloride is a NUDT5 inhibitor with a human target IC₅₀ of 29 nM, ~690-fold selectivity over MTH1 in vitro, and selective functional inhibition over other NUDIX hydrolases including NUDT9.TH5427 hydrochloride binds to the active site of NUDT5, blocking enzymatic activity related to ADP-ribose metabolism and PAR-derived ATP synthesis.TH5427 hydrochloride blocks progestin-dependent nuclear ATP synthesis, impairs progestin-induced chromatin remodeling, inhibits histone H1 displacement, disrupts progestin-dependent gene regulation, and abrogates progestin-dependent proliferation in breast cancer cells.TH5427 hydrochloride functions as a versatile probe to study nuclear ATP dynamics and ADP-ribose-related metabolism in cells.TH5427 hydrochloride engages NUDT5 at physiological temperatures, as demonstrated by Drug Affinity Responsive Target Stability (DARTS) assay.TH5427 hydrochloride stabilizes NUDT5 against thermal denaturation in cell lysates and intact cells, as shown by cellular thermal shift assay (CETSA).TH5427 hydrochloride functionally inhibits NUDT5 activity, leading to downstream effects on oxidative DNA damage and DNA replication in triple-negative breast cancer (TNBC) cells.TH5427 hydrochloride suppresses proliferation of TNBC cells without inducing cell death or apoptosis, slows DNA replication in TNBC cells, promotes accumulation of oxidative DNA lesions, and triggers DNA damage response in TNBC cells.TH5427 hydrochloride suppresses growth of TNBC cells in vitro, inhibits growth of TNBC xenograft tumors in nude mice in vivo, and shows greater potency against TNBC cell lines compared to ER-positive and normal-like breast cell lines.TH5427 hydrochloride can be used for the research of breast cancer and triple-negative breast cancer.

Rucaparib-d₃ (AG014699-d₃) is the deuterated -labeled Rucaparib (HY-10617A). Rucaparib (AG014699) is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a K_i of 1.4 nM for PARP1. Rucaparib is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib has the potential for castration-resistant prostate cancer (CRPC) research.

PARP1/c-Met-IN-1 (Compound 16) is a selective dual inhibitor for PARP1 and c-Met, with IC₅₀s of 3.3 and 32.2 nM, respectively. PARP1/c-Met-IN-1 induces cell apoptosis and cell cycle arrest in G2/M phase in MDA-MB-231 cells. PARP1/c-Met-IN-1 exhibits antitumor activity in mice.

Castalagin is an orally active natural product with multiple biological activities including antibacterial activity against bacteria and anti-leishmanial activity against Leishmania aethiopica. Castalagin exhibits inhibitory activity against PARP1 and DNA topoisomerase II, with an IC₅₀ of 0.86 μM for bovine PARP1. Castalagin reduces poly (ADP-ribosyl) ation modification in cells. Castalagin binds to the cell envelope of Ruminococcus bromii, increases the ratio of CD8⁺/FOXP3⁺CD4⁺ T cells in the tumor microenvironment, and acts as a prebiotic to enhance the activity of anti-PD-1 therapy. Castalagin induces morphological changes in Leishmania aethiopica promastigotes and inhibits their proliferation. Castalagin inhibits PBP2a-mediated peptidoglycan layer stabilization, disrupts bacterial peptidoglycan assembly, and inhibits and disintegrates bacterial biofilms. Castalagin can be used in research related to diseases such as cancer, leishmaniasis, and bacterial infections.

EGFR/PARP-1-IN-1 is a dual EGFR and PARP-1 inhibitor with IC₅₀ values of 64 nM and 12 nM, respectively. EGFR/PARP-1-IN-1 binds to the ATP-binding pocket of EGFR and interacts with the catalytic domain of PARP-1, inhibiting kinase and enzymatic activity via hydrogen bond formation with key residues in both targets. EGFR/PARP-1-IN-1 induces apoptosis through the endogenous mitochondrial pathway, arrests the cell cycle at the G2 phase, and inhibits cell proliferation. EGFR/PARP-1-IN-1 can be used for research on triple-negative breast cancer.

S-Petasin is a phosphodiesterase (PDE) inhibitor with IC₅₀ values of 25.5 μM and 17.5 μM for PDE3 and PDE4, respectively. S-Petasin inhibits cholesterol side-chain cleavage enzyme, 11β-hydroxylase, PPAR-γ, and iNOS induction at RNA and protein levels. S-Petasin induces apoptosis, activates caspases, cleaves PARP, modulates mitochondrial membrane permeability, and regulates BCL2/BAX, p53, Bcl-XL, MMP-2, MMP-9, p21, CDK4, and cyclin D1 expression. S-Petasin reduces inflammatory cell accumulation, cytokine and IgE levels, and enhances serum IgG2a levels. S-Petasin relaxes isolated sensitized guinea pig trachealis and exhibits gastrointestinal anti-spasmodic activity. S-Petasin reduces tonsillitis severity and asthmatic attack frequency. S-Petasin can be used for the research of prostate cancer, obesity, melanoma, allergic asthma, asthma, and peritonitis.