drosophila

Selisistat (EX-527) 是一种去乙酰化酶 SIRT1 的抑制剂 (IC50=38 nM)，具有有效性和特异性。Selisistat 可以用于神经系统疾病如亨廷顿舞蹈病的研究。

AGK7 是 sirtuin 2 (SIRT2) 抑制剂。它在体外和帕金森病果蝇模型中均能抑制多巴胺能细胞的凋亡。在帕金森病细胞模型中，它改善了 α-突触核蛋白毒性和修饰的包涵体形态

Thiacloprid 属于氯烟碱类杀虫剂，主要用于防治蔬菜和果园中的蚜虫。它会破坏 DNA 的稳定性，通过疏水或氢相互作用，结合到小沟槽中，改变 DNA 的结构和稳定性。

Moxnidazole 是一种5-硝基咪唑，在微生物试验和果蝇中具有诱变性，诱导小鼠体细胞的遗传改变。

Chlorantraniliprole (Rynaxypyr) 是一种杀虫剂，能够有效地、选择性地激活鱼尼丁受体 (ryanodine receptor)，对黑腹果蝇和烟芽夜蛾的 ryanodine 受体 EC50 值分别为 40 nM 和 50 nM，对其选择性是对小鼠骨骼肌 2C12 细胞 ryanodine 受体 (EC50，14 μM) 的 300 多倍。

Antennapedia Peptide TFA (188842-14-0 free base) 是一种 16 个氨基酸的肽，是细胞穿透肽家族的成员，最初来源于果蝇转录因子 Antennapedia 的 60 个氨基酸长的同源域。

Lotilaner 是杀寄生虫剂，是非竞争性的昆虫GABACl 受体拮抗剂，对果蝇 GABA 受体的IC50值为 23.84 nM。对家犬的 GABAA 无明显作用。

AChE BChE-IN-25 (Compound 6e) 是一种口服有效的hAChE和eqBChE抑制剂，其IC50分别为7.9 nM和0.79 nM。AChE BChE-IN-25 具有抗氧化活性，能够清除自由基，IC50为22.91 μM。此化合物通过降低果蝇阿尔茨海默症模型中的线粒体和细胞氧化应激体现神经保护作用，并能改善小鼠模型中Scopolamine引起的空间和认知记忆障碍。

AD57, as polypharmacological cancer therapeutic, is designed to regulate multiple targets related to cancer blocks the receptor tyrosine kinase RET in Drosophila (IC50: 2 nM). AD57 effectively suppresses tyrosine kinase RET, weakens the activity of numero

Xanthumin is a naturally occurring insect development inhibitor against Drosophila melanogaster. Xanthumin is also an antibacterial compound.

Neomyosuppressin is a myoinhibiting neuropeptide isolated from the grey fleshfly, Neobellieria bullata and Drosophila.

Auten-99 HBr (Auten-99) 是新型肌管蛋白磷酸酶 Jumpy( MTMR14) 的抑制剂，可通过血脑屏障，具有强大的神经保护作用。

ML207 inhibits lipid storage in Drosophila melanogaster.

Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001). Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4 References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001).

Ceramide phosphoethanolamine (CPE) is an analog of sphingomyelin that contains ethanolamine rather than choline as the head group. It is the principal membrane phospholipid in invertebrates such as Drosophila, which lacks sphingomyelin. It is only produced in small amounts in mammalian cells, accounting for approximately 0.02 mol% of total phospholipids in mouse testis and brain. In Drosophila, CPE is biosynthesized by CPE synthase from ceramide and cytidine diphosphate-ethanolamine in the Golgi lumen. In mammals, it is biosynthesized by sphingomyelin synthase 2 (SMS2) in the plasma membrane and by sphingomyelin synthase-related protein (SMSr) in the endoplasmic reticulum (ER). In Drosophila, CPE has a role in glial ensheathment of axons. Disrupting CPE synthesis by depleting SMSr in vitro in mammalian cells leads to an accumulation of ER ceramides, which are then mislocalized to the mitochondria, inducing apoptosis. However, ceramide levels are not altered in transgenic mice lacking SMSr catalytic activity. CPEs (bovine) is a mixture of CPEs with variable N-acyl chain lengths.

C2 Ceramide (d14:1 2:0) is a bioactive sphingolipid. Dietary administration of C2 ceramide (d14:1 2:0) (100 μM) induces lipotoxic cardiomyopathy via increasing diastolic and systolic diameter as well as reducing fractional shortening and the number of normal cardiac contractile events in Drosophila.

Binucleine 2 is an isoform-specific and ATP-competitive inhibitor of Drosophila Aurora B kinase (Ki = 0.36 μM), a kinase involved in cell division. It is specific for Drosophila Aurora B kinase, inhibiting it in a dose-dependent manner, with minimal inhibition of human or X. laevis Aurora B kinases at concentrations up to 100 μM. Binucleine 2 induces mitotic and cytokinesis defects in Drosophila Kc167 cells. It prevents Drosophila S2 cells from assembling a contractile ring during cell division when used at a concentration of 40 μM but does not affect ring ingression, suggesting that Aurora B kinase activity is not required for that step.

(9Z)-Tricosene is a pheromone released by insects, including D. melanogaster, M. domestica (house fly), and A. mellifera L. (honey bee). In Drosophila, it induces aggregation behavior and is an oviposition guidance cue for females. Due to its aggregation-inducing activity, it is used as a bait pesticide to attract insects to traps. The mechanism of action in Drosophila is the activation of antennal basiconic Or7a receptors. It is also highly produced by honey bees during the waggle dance, which is a complex communication process used to alert nest-mates of the location and profitability of a food source. When injected into a hive, (9Z)-tricosene induced foraging behavior.

Potent Smo antagonist (IC50 = 5 nM). Attenuates the leukemia-initiation potential of AML cells in a serial transplantation mouse model. Also eliminates self-propagation capacity of AML cells. Munchhof et al (2011) Discovery of PF-04449913, a potent and orally bioavailable inhibitor of smoothened. ACS Med.Chem.Lett. 3 106 PMID:24900436 |Fukushima et al (2016) Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Cancer Sci. 107 1422 PMID:27461445 |Giordani et al (2016) The human Smoothened inhibitor PF-04449913 induces exit from quiescence and loss of multipotent Drosophila hematopoietic progenitor cells. Oncotarget 7 55313 PMID:27486815

Unsaturated, long-chain hydrocarbons are found on the cuticles of insects and can act as pheromones. In mature Drosophila melanogaster, certain cuticular hydrocarbons are sexually dimorphic: males synthesize 23- and 25-C monoenes and females produce 27- and 29-C dienes. Each of these lipids plays specific roles in regulating male sexual behavior, with dienes stimulating courtship. 7(Z),11(Z)-Pentacosadiene is a 25-C hydrocarbon that is found in low abundance on cuticles of mature Drosophila females. Depletion of a female-specific elongase (eloF), which leads to an increase in 7(Z),11(Z)-pentacosadiene along with a parallel decrease in 7,11-nonacosadiene, significantly reduces copulation in Drosophila. This raises the possibility that 7(Z),11(Z)-pentacosadiene may act as an anti-aphrodisiac.

7(Z)-Pentacosene is an unsaturated cuticular hydrocarbon that acts as a contact sex pheromone in fruit flies. In different species and genotypes of Drosophila, it can be found on both males and females. Pentacosene may stimulate copulation either by itself at high concentrations or when combined with other alkenes. Interestingly, the absolute level of pentacosene increases in Drosophila females immediately after copulation.

7(Z)-Tricosene是一种昆虫信息素和内源性代谢物，用于交配和种间识别。

6-Aminophenanthridine is an antiprion agent. It inhibits prion formation in yeast- and mammalian-based screening assays when used alone and, to a greater extent, when used in combination with the α2-adrenergic receptor agonist guanabenz . 6-Aminophenanthridine (300 μM) inhibits protein folding activity of the ribosome (PFAR) by directly competing with protein substrates for the active site and decreases the yield of refolded protein without affecting the refolding rate. It prevents progressive wing position defects in a Drosophila model of oculopharyngeal muscular dystrophy (OPMD) when larvae are raised on medium containing doses ranging from 300 to 400 μM and in adults following dietary administration of 1-3 mM doses. 6-Aminophenanthridine also reduces muscle degeneration and decreases the number of nuclear inclusions in thoracic muscle in a Drosophila model of OPMD.

C2-8 is an inhibitor of polyglutamine (polyQ) aggregation (IC50s = 25 and 0.05 μM for recombinant HDQ51 and in PC12 cells, respectively). It also inhibits polyQ aggregation in organotypic hippocampal slice cultures isolated from R6 2 transgenic mice and reduces neurodegeneration in a dose-dependent manner in a Drosophila model of Huntington's disease. C2-8 (100 and 200 mg kg) reduces huntingtin aggregate size, reduces neuronal atrophy, and improves motor performance in a rotarod test in the R6 2 transgenic mouse model of Huntington's disease.