lethality

AZD5305 is a potent, selective and oral active PARP inhibitor.

SSJ-183 is a low-toxicity and orally available and anti-malarial drug with an IC50 = 7.6 nM against P. falciparum and no lethality at doses up to 2000 mg kg po.

Syrosingopine is a dual inhibitor of MCT1 and MCT4, 60 times more potent against MCT4, preventing lactate and H+ efflux. Syrosingopine is an orally available antihypertensive drug with potential for cancer research in combination with metformin.

Adenosine N1-oxide (1-Oxoadenosine), which is found in royal jelly, inhibited the secretion of inflammatory mediators by activated macrophages and reduced lethality in lipopolysaccharide (LPS)-induced endotoxin shock.

CM-10-18 is a potent inhibitor of ER α-glucosidase, demonstrating superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever, and efficiently protecting against the lethality of dengue virus infection in mice.

3-Acetyldeoxy nivalenol-13C17is intended for use as an internal standard for the quantification of 3-acetyldeoxy nivalenol by GC- or LC-MS. 3-Acetyldeoxy nivalenol is a mycotoxin that has been found inF. graminearum.1In vivo, 3-acetyldeoxy nivalenol (40 mg/kg) induces duodenal and splenic cell necrosis, as well as lethality (LD50= 70 mg/kg) in mice.2 1.Jiao, F., Kawakami, A., and Nakajima, T.Effects of different carbon sources on trichothecene production and Tri gene expression by Fusarium graminearum in liquid cultureFEMS Microbiol.Lett.285(2)212-219(2008) 2.Schiefer, H.B., Nicholson, S., Kasali, O.B., et al.Pathology of acute 3-acetyldeoxynivalenol toxicity in miceCan. J. Comp. Med.49(3)315-318(1985)

4-deoxy Nivalenol-13C15is intended for use as an internal standard for the quantification of 4-deoxy nivalenol by GC- or LC-MS. 4-deoxy Nivalenol is a trichothecene mycotoxin that has been found inFusarium.1It binds to eukaryotic ribosomes and inhibits protein synthesis in mice when administered at doses ranging from 5 to 25 mg/kg. 4-deoxy Nivalenol (0.1 and 0.2 mg/kg) induces emesis in pigs and decreases feed consumption in pigs when administered at a dose of 40 ppb in the diet.2It induces lethality in mice (LD50= 46-78 mg/kg).34-deoxy Nivalenol has been found inF. graminearum-infected cereal grains such as wheat, barley, and corn. 1.Pestka, J.J., and Smolinski, A.T.Deoxynivalenol: Toxicology and potential effects on humansJ.Toxicol.Environ.Health B.Crit.Rev.8(1)39-69(2005) 2.Forsyth, D.M., Yoshizawa, T., Morooka, N., et al.Emetic and refusal activity of deoxynivalenol to swineAppl. Environ. Microbiol.34(5)547-552(1977) 3.Pestka, J.J.Deoxynivalenol: Mechanisms of action, human exposure, and toxicological relevanceArch. Toxicol.84(9)663-679(2010)

Aflatoxin G1-13C17is intended for use as an internal standard for the quantification of aflatoxin G1by GC- or LC-MS. Aflatoxin G1is a mycotoxin that has been found inA. terricola.1In vivo, aflatoxin G1is lethal to ducklings (LD50= 1.18 mg/kg).2It induces hepatocellular carcinoma tumor formation and lethality in rats when administered at doses of 1.4 and 3 mg/animal, respectively. Aflatoxin G1also inhibits liver and kidney succinate dehydrogenase and fumarase, as well as kidney cytochrome oxidase, NADH oxidase, α-glycerophosphate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase in rats.3 1.Moubasher, A.H., el-Kady, I.A., and Shoriet, A.Toxigenic Aspergilli isolated from different sources in EgyptAnn. Nutr. Aliment.31(4-6)607-615(1977) 2.Wogan, G.N., Edwards, G.S., and Newberne, P.M.Structure-activity relationships in toxicity and carcinogenicity of aflatoxins and analogsCancer Res.31(12)1936-1942(1971) 3.Bai, N.J., Pai, M.R., and Venkitasubramanian, T.A.Mitochondrial function in aflatoxin toxicityIndian J. Biochem. Biophys.14(4)347-349(1977)

Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg/kg. Nitisinone (3 mg/kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH-/-mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg/kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)

CAY10760 is an inhibitor of the protein-protein interaction between RAD51 recombinase and BRCA2 (EC50= 19 μM in a cell-free competitive ELISA).1It decreases homologous recombination by 54% in wild-typeBRCA2-expressing BxPC-3 pancreatic cancer cells when used at a concentration of 20 μM. CAY10760 (20 μM) decreases proliferation of BxPC-3, as well as mutantBRCA2-expressing Capan-1, cancer cells when used alone or in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib . 1.Bagnolini, G., Milano, D., Manerba, M., et al.Synthetic lethality in pancreatic cancer: Discovery of a new RAD51-BRCA2 small molecule disruptor that inhibits homologous recombination and synergizes with olaparibJ. Med. Chem.63(5)2588-2619(2020)

Diquat dibromide is a water-soluble herbicide that causes rapid and profound systemic toxicity.Diquat dibromide induces acute kidney injury with high lethality.3-Phosphoglyceraldehyde has been shown to be effective in the treatment of LPS-induced ALI.

PIP4K-IN-a131 is a selective inhibitor of PIP4K lipid kinases, demonstrating IC50 values of 1.9 μM for PIP4K2A and 0.6 μM for PIP4Ks. It exhibits cancer-selective lethality by simultaneously blocking the lipid kinase PIP4Ks and mitotic pathways.

Antitubercular agent-19 is an antitubercular agent. antitubercular agent-19 showed good antitubercular effects against MTB H37Rv and MDR-MTB (MIC <0.016 μg ml). antitubercular agent-19 showed low cytotoxicity and relatively high acute lethality in BALB c mice. Antitubercular agent-19 exhibited low cytotoxicity and relatively high acute lethal toxicity in BALB c mice.

Deoxycytidine triphosphate trisodium salt (2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE TRISODI) contributes to antibiotic lethality in stationary-phase mycobacteria.

Endotoxin Inhibitor TFA is a synthetic peptide that exhibits high-affinity binding to lipid A, effectively detoxifying LPS and impeding LPS-induced cytokine release in vivo. It also suppresses the febrile response to LPS while demonstrating minimal toxicity and lethality [1].

ATR-IN-23 (Compound 34), a potent and selective ATR inhibitor, exhibits an IC50 of 1.5 nM, has demonstrated antiproliferative effects on LoVo cells, and induces synthetic lethality in HT-29 cells, suggesting its utility in researching DNA damage response (DDR)-deficient cancers [1].

r8 Bid BH3, a biologically active peptide, is a pro-apoptotic member of the BH3-only subset within the BCL-2 family proteins, pivotal in regulating apoptosis. This compound exhibits lethality towards Bcl-2-expressing human leukemia cell lines, indicating its promise as a potential cancer therapeutic. The peptide is conjugated with poly-D-arginine (denoted by rrrrrrrr), enhancing cellular uptake.

Ssm Spooky Toxin, derived from Scolopendra mutilans, exhibits potent lethality affecting both hematological and respiratory systems primarily through the inhibition of KCNQ (voltage-gated potassium channel family 7) channels. It demonstrates IC50 values of 2.8 μM for Kv7.4, 5.26 μM for Kv1.3, and 0.1-0.3 M for the Shal channel, respectively. Additionally, this toxin impedes cytokine production by selectively targeting the KV1.3 channel in T cells and is crucial for the centipede's circulatory system functions [1] [2] [3].

Byssochlamic acid, a mycotoxin identified in the agricultural fungal pathogen B. fulva, exhibits lethality in mice with an LD50 of 94 mg/kg.

Spirotetramat is an insecticide that demonstrates efficacy against C. pyrinymphs in vitro (LC50= 6.51-12.53 mg AI/L) and achieves a 99.2% mortality rate in C. pyrinymphs within European pear (P. communis) fields 15 days post-application at a dosage of 27 g/hectare. Additionally, it reduces embryonic viability and nymph survival in O. insidiosus. Spirotetramat exhibits aquatic toxicity by altering protein levels in organisms, specifically by increasing glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels, decreasing malondialdehyde (MDA) levels, and causing lethality in Chinese toad (B. gargarizans) tadpoles (LC50= 6.98 mg/L). Its formulations are utilized in agricultural insect control. Spirotetramat is marketed exclusively for research and analytical applications, formulated for controlled laboratory settings without the availability of bulk sizes.

Cyclo(Pro-Leu) (Cyclo-L-prolyl-L-leucine) is a marine-derived natural product with brine shrimp lethality.

Acetyl Ser-Asp-Lys-Pro is formed in bone marrow cells by enzymatic processing of thymosin β4. It inhibits the entry of pluripotent hemopoietic stem cells into S-phase of the cell cycle and protects against Ara-C lethality in mice.