genotoxic

Inauhzin (INZ)(INZ) is a novel small molecule that effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human Y cells without causing apparently genotoxic stress(IC50=3 uM, in A549 cell).

Compound 2 (MRV03-068) is a selective colibactin-activated peptidase (ClbP) inhibitor, preventing the genotoxic effects of colibactin on eukaryotic cells, with potential applications in colorectal cancer research [1].

Riddelline is a potent genotoxic agent in vitro and induces significant elevations in unscheduled DNA synthesis and S-phase synthesis in rat liver.

5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4References 5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4 References

2,5-Dimethyl-3(2H)-furanone (2,5-Dimethyl-2,3-dihydrofuran-3-one) is a non-genotoxic flavoring substance [1].

Illudin S (ILS) is a fungal sesquiterpene secondary metabolite with potent genotoxic and cytotoxic properties.

Djalonensone (Alternariol monomethyl ether), an Alternaria toxin, is a strong mutagen in Escherichia coli strain ND-160. Alternariol monomethyl ether has genotoxic properties, it can cause oxidative DNA damage. It also possesses cytotoxic and immunosuppressive properties.

Compound 3 (MRV03-069) is a selective inhibitor of colibactin-activated peptidase (ClbP), effectively impeding colibactin's genotoxic effects on eukaryotic cells, with potential applications in colorectal cancer research [1].

Lucidin primeveroside (Lucidin 3-O-primeveroside) is a natural product isolated from the root powder of akane (Rubia akane) and can be used as a coloring agent and a food pigment. Lucidin primeveroside can be metabolically converted to genotoxic compound Lucidin in mice.

Dibromochloroacetaldehyde, a trihalogenated acetaldehyde compound, is present as a byproduct in drinking water. It exhibits genotoxic properties.

Levofloxacin N-oxide is an inactive metabolite of the antibiotic levofloxacin . Levofloxacin N-oxide is also a degradation product of levofloxacin that is formed through exposure to daylight or hydrogen peroxide.

Colibactin, a complex secondary metabolite synthesized by certain genotoxic Escherichia coli strains in the gut, holds potential for colorectal cancer research [1].

1-Hydroxyanthraquinone is an anthraquinone that has been found in Morinda officinalis and has genotoxic and carcinogenic activities. 1-Hydroxyanthraquinone generates strong DNA repair response.

Bromochloroacetaldehyde is a dihalogenated acetaldehyde compound that is commonly found as a byproduct in drinking water. It exhibits genotoxic properties.

Pidnarulex HCl is the salt form of CX-5461, a first-in-class non-genotoxic small molecule targeted inhibitor of RNA polymerase I (Pol I) that activates the p53 pathway without causing DNA damage. CX-5461 selectively inhibits rRNA synthesis by Pol I in the nucleolus, but does not inhibit mRNA synthesis by RNA Polymerase II (Pol II) and does not inhibit DNA replication or protein synthesis. Inhibition of Pol I results in nucleolar stress and release of ribosomal proteins (RP) from the nucleolus. The RP bind to Mdm2 and liberate p53 to orchestrate apoptosis in cancer cells. CX-5461 demonstrates a favorable preclinical profile, potently and selectively kills cancer cells, demonstrates robust in vivo efficacy in multiple models, and has demonstrated oral bioavailability in multiple species.

CYP2C19-IN-1 is a potent, non-genotoxic, non-hepatotoxic inhibitor of CYP2C19. CYP2C19-IN-1 inhibits RNA-dependent RNA polymerase (RdRP) (Ki: 6.16 μM) and can be used to study Zika virus (ZIKV) infection.

N-Acetylglycine is a minor constituent of food that is not genotoxic or acutely toxic and is capable of being used in biological studies of mimetic peptides.N-Acetylglycine acts as a blocker of the N-terminus of a peptide.3-Hydroxyanthranilic acid is a competitive succinate dehydrogenase inhibitor.

Diaveridine (AI3-23935) (DVD) is a popular antibacterial synergist that is widely used in combination with sulfonamide. It has been reported to be genotoxic to mammalian cells, but more studies are required to clarify this.

MSN-50, an inhibitor of Bax and Bak oligomerization, inhibits liposome permeabilization, prevents genotoxic cell death and promotes neuroprotection.

Homobaldrinal has low toxic activity. It has genotoxic activity in the Salmonella/microsome test and the SOS-chromotest.

Cyanazine, a triazine herbicide, is utilized for effective control of a diverse range of grass and broadleaf weeds. It has been scientifically validated as non-genotoxic.

NiCur blocks CBP HAT activity and downregulates p53 activation upon genotoxic stress. NiCur is a potent and selective inhibitor of CBP histone acetyltransferase (HAT) with an IC 50 value of 0.35 μΜ. NiCur can be used to perform mechanistic studies without affecting target proteins expression [1].

Arecaidine propargyl ester is an agonist of M2muscarinic acetylcholine receptors (mAChRs).1It selectively binds to M2over M1, M3, M4, and M5mAChRs in CHO cells expressing the human receptors (Kis = 0.0871, 1.23, 0.851, 0.977, and 0.933 μM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD2= 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 μM.2Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED25= 1.9 nmol/kg).3It is toxic to house flies (Musca) when administered at a dose of 75 μg/fly.4 1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2’R,3’S,5’R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)

MX106 is a survivin inhibitor which induces degradation of XIAP and/or cIAP1, and suppresses genotoxic NF-kappaB activation.

N-Nitroso fluoxetine is a derivative of fluoxetine.1It is genotoxic toS. typhimuriumwhen used at concentrations ranging from 0.06 to 0.12 mg/ml.

Jatropham is a natural compound isolated from lily of the valley. It has been shown to have the potential to modulate and reduce the cytotoxic and genotoxic/labile effects of zeocin.

Methapyrilene fumarate is a histamine H1 antagonist with sedative action used as a hypnotic and in allergies. It is a hepatocarcinogen in sufficiently high doses, inducing mutations through an indirect genotoxic mechanism; e.g., via an oxidative mechanism or interaction with chromosomal proteins.

Propionic-2,2-d2 acid is a deuterated compound of Propionic acid. Propionic acid has a CAS number of 79-09-4. Propionic acid (PA) is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is irritant but produces no acute systemic effects and has no demonstrable genotoxic potential.Propionic aciduria is one of the most frequent organic acidurias, a disease that comprise many various disorders. The outcome of patients born with Propionic aciduria (genetic disorder) is poor intellectual development patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not necessarily prevented neurological and various visceral complications. These results emphasize the need for permanent metabolic follow-up whatever the therapeutic strategy. Decreased early mortality, less severe symptoms at diagnosis, and more favorable short-term neurodevelopmental outcome were recorded in patients identified through expanded newborn screening.

Azobenzene is a phototrigger that can be used to design and synthesize a variety of photoresponsive systems.Azobenzene is genotoxic and induces aggressive sarcomas of the spleen and other abdominal organs.

RK-701, a highly selective and non-genotoxic G9a inhibitor, exhibits an IC 50 value of 23-27 nM. It selectively up-regulates HbF, γ-Globin, and BGLT3 expression while down-regulating H3K9me2 expression. Additionally, RK-701 inhibits BCL11A and ZBTB7A.

MX107 is a survivin inhibitor which induces degradation of XIAP and/or cIAP1, and suppresses genotoxic NF-kappaB activation.

Cylindrospermopsin, a tricyclic uracil derivative, is a cyanobacterial toxin that was first discovered in an algal bloom contaminating a local drinking supply on Palm Island in Queensland, Australia after an outbreak of a mysterious disease. Cylindrospermopsin targets protein and glutathione synthesis in hepatocytes (IC50s = 1.3 and 2.4 µM, respectively), leading to cell death. [1] It has been shown to inhibit the activity of the uridine monophosphate synthase complex with a Ki value of 10 µM.[2] Cylindrospermopsin is genotoxic, inducing DNA damage as evidenced by double strand breaks and reducing cell viability in HepG2 cells at 0.1-0.5 µg/ml.[3]

4-Hydroxynonenal (4-HNE) (4-HNE) is an oxidative/nitrosative stress biomarker. It is a substrate and an inhibitor of acetaldehyde dehydrogenase 2 (ALDH2).

1,3-Dithiane (1,3-Dithian) is a protected formaldehyde anion equivalent that could serve as a useful labeled synthon. 1,3-Dithiane is also a sulfur-containing Maillard reaction products found in boiled beef extracts.

Propionicacid-d5 is a deuterated compound of Propionicacid. Propionicacid has a CAS number of 79-09-4. Propionic acid (PA) is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is irritant but produces no acute systemic effects and has no demonstrable genotoxic potential.Propionic aciduria is one of the most frequent organic acidurias, a disease that comprise many various disorders. The outcome of patients born with Propionic aciduria (genetic disorder) is poor intellectual development patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not necessarily prevented neurological and various visceral complications. These results emphasize the need for permanent metabolic follow-up whatever the therapeutic strategy. Decreased early mortality, less severe symptoms at diagnosis, and more favorable short-term neurodevelopmental outcome were recorded in patients identified through expanded newborn screening.

4'-Methylacetophenone can be used as a fragrance material. It is wildly occurred in volatile compounds in food and in some natural complex substances.

Ethylene glycol dimethacrylate, a methacrylate monomer, demonstrates cytotoxic and genotoxic impacts on human gingival fibroblasts (HGFs), elevating intracellular reactive oxygen species (ROS) levels, inducing DNA damage, enhancing apoptosis, and triggering cell cycle arrest in the G1/G0 phase [1].

1. Lucidin (NSC-30546) and its derivatives are genotoxic, it is mutagenic at the hypoxanthine-guanine phosphoribosyl transferase gene locus.

MRV03-037, a selective colibactin-activated peptidase (ClbP) inhibitor, effectively inhibits the genotoxic effects of Colibactin on eukaryotic cells by blocking the production of gut bacterial genotoxins [1].

Sunset Yellow FCF (Sunset yellow) is an orange azo dye with pH-dependent absorbance.Sunset Yellow FCF is used in food, cosmetics and pharmaceuticals.It is used as a colorant food additive in many food products.They may be cytotoxic and genotoxic, so care must be taken when using these materials as food additives.