INO-1001 a novel potent PARP inhibitor with an IC50 of 3 nM.
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A novel class of substituted spiro [quinazoline-2,1'-cyclohexane] derivatives as effective PPAR-1 inhibitors: molecular modeling, synthesis, cytotoxic and enzyme assay evaluation.
Molecular docking simulation study was carried out to design a novel series of spiro [(2H, 3H)quinazoline-2,1'-cyclohexan]-4(1H)-one derivatives as a new class of effective PARP-1 inhibitors. Spi...Read More
In a search for new inhibitors of the nuclear enzyme poly(ADP-ribose) synthetase, it was found that various benzamides substituted in the 3-position were the most inhibitory compounds found to date. T...Read More
Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells.
Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an early response of cells exposed to DNA-damaging compounds such as nitric oxide (NO) or reactive oxygen intermediates (ROI). Ex...Read More
U937 human myeloid leukemia cells respond to mild treatment with hydrogen peroxide and hyperthermia by undergoing apoptosis, an active mode of cell suicide. Higher concentrations of hydrogen peroxide,...Read More
Inhibitors of poly(ADP-ribose) polymerase block nitric oxide-induced apoptosis but not differentiation in human leukemia HL-60 cells.
Previous studies have shown that chemically generated nitric oxide (NO) can induce human leukemia HL-60 cells to undergo monocytic differentiation. We show here that exposure of HL-60 cells to chemica...Read More
Xerostomia as a result of salivary gland damage is a permanent and debilitating side effect of radiotherapy for head and neck cancers. Effective treatments for protecting, or restoring, salivary gland...Read More
Poly(ADP-ribose) polymerase inhibition improves erectile function by activation of nitric oxide/cyclic guanosine monophosphate pathway in diabetic rats.
Endothelial dysfunction-induced abnormalities of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the corpus cavernosum are thought to be the main factors involved in t...Read More
Inverse susceptibility to oxidative death of lymphocytes obtained from Alzheimer's patients and skin cancer survivors: increased apoptosis in Alzheimer's and reduced necrosis in cancer.
A paucity of cancer in individuals with Alzheimer's disease (AD) and low rates of AD in cancer survivors has been reported in epidemiological studies. Deregulation in opposite directions of biolo...Read More
Increased poly(ADP-ribosyl)ation in peripheral leukocytes and the reperfused myocardium tissue of rats with ischemia/reperfusion injury: prevention by 3-aminobenzamide treatment.
The overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is considered a final common effector in ischemia/reperfusion (I/R) injury. The aim of the current study was to examine the ...Read More
Genotoxic stress and activation of novel DNA repair enzymes in human endothelial cells and in the retinas and kidneys of streptozotocin diabetic rats.
Mammalian excision repair cross-complementing 1 (ERCC1) and ERCC4 (a.k.a xeroderma pigmentosum complementation group F) are nucleotide excision repair enzymes, which excise the 5' end of damaged ...Read More
The study aimed to investigate the effect of inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) activity on tau phosphorylation in HEK293/tau441 cells and its mechanism. HEK293/tau441 cells were tre...Read More
Centrosome amplification (also known as centrosome overduplication) is common in cancer cells and can be induced by DNA damaging agents. However, the mechanism and significance of centrosome amplifica...Read More
Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor-β Induced Smad3 activation in vascular smooth muscle cell.
Transforming growth factor type-β (TGF-β)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-β signaling-induced vascular fibrosis...Read More
Poly(ADP-ribose) polymerase-1 (PARP1) inhibitors are emerging as an important class of drugs for treating BRCA-deficient cancers. Recent discoveries have shown that PARP1 inhibitors may treat other ca...Read More
Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis.
Asbestos is known to induce malignant mesothelioma (MM) and other asbestos-related diseases. It is directly genotoxic by inducing DNA strand breaks and cytotoxic by promoting apoptosis in lung target ...Read More
Association of sperm morphology and the sperm deformity index (SDI) with poly (ADP-ribose) polymerase (PARP) cleavage inhibition.
Apoptosis was induced in immature and mature sperm in the presence or absence of poly (ADP-ribose) polymerase (PARP) inhibitor. The association of cleaved (cPARP) with sperm morphology was examined us...Read More
The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells
Pharmacological inhibition of DNA repair pathways has been emerging as an effective tool for cancer treatment. Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair and transcriptional regulati...Read More
Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents.
In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1-6) as potential anticancer agents. Cytotoxicity was evaluated agai...Read More
Poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, protects against experimental immune ovarian failure in mice.
The activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) may play an important role in numerous pathological conditions. The aim of the present study was to clarify the role of PARP in ...Read More
3-Aminobenzamide protects primary human keratinocytes from UV-induced cell death by a poly(ADP-ribosyl)ation independent mechanism.
Poly(ADP-ribosyl)ation (PARylation) is a NAD(+)-dependent protein modification carried out by PARP [poly(ADP-ribose) polymerase] enzymes. Here we set out to investigate whether PARylation regulates UV...Read More
8-Oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species, is associated with carcinogenesis and neurodegeneration. Although the mechanism by which 8-oxoG causes carcinogenesis is w...Read More
The incidence of progressive multifocal leukoencephalopathy (PML) has increased due to the AIDS pandemic, hematological malignancies, and immunosuppressive therapies. Recently, the number of cases of ...Read More
Nerve growth factor (NGF) is a critical secreted protein that plays an important role in development, survival, and function of the mammalian nervous system. Previously reports suggest that endogenous...Read More
Inhibition of Poly(ADP-Ribose) Polymerase Attenuates Acute Kidney Injury in Sodium Taurocholate-Induced Acute Pancreatitis in Rats.
The aim of our present study was to investigate the efficacy of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in the development of acute kidney injury in an experimental model of se...Read More
Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells.
Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to i...Read More
Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.
Migraine is one of the risk factor for ischemic stroke. The purpose of this study was to examine the effect of lomerizine, a prophylactic drug for migraine, on H(2)O(2)-induced cell death of hippocamp...Read More
Effects of 3-aminobenzamide on unilateral testicular ischemia-reperfusion injury: what is the role of PARP inhibition?
The therapeutic effects of poly(adenosine diphosphate-ribose) polymerase inhibition by 3-aminobenzamide (3-AB) were investigated in testicular ischemia-reperfusion (I/R) injury, using sperm analysis a...Read More
Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs.
Intrigued by the dynamics of the seemingly contradictory yet integrated cellular responses to the requisites of preserving telomere integrity while also efficiently repairing damaged DNA, we investiga...Read More
Changes in protein turnover are among the dominant metabolic changes during aging. Of special importance is the maintenance of nuclear protein homeostasis to ensure a coordinated cellular metabolism. ...Read More
Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone.
Novel indeno[1,2-c]isoquinolinone derivatives were synthesized and evaluated as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). These potent nonmutagenic PARP-1 inhibitors pos...Read More
Design, synthesis, and cytoprotective effect of 2-aminothiazole analogues as potent poly(ADP-ribose) polymerase-1 inhibitors.
A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4-10) based on a constructed three-dimensional pharmacophore model. After synthesis,...Read More
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Discovery and SAR of novel, potent and selective hexahydrobenzonaphthyridinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).
A novel hexahydrobenzonaphthyridinone PARP-1 pharmacophore is reported, subsequent SAR exploration around this scaffold led to selective PARP-1 inhibitors with low nanomolar enzyme potency, displaying...Read More
We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC(50)?=?5.75?μM) could be transformed into highly active deriv...Read More