Malvidin-3-O-arabinoside chloride ameliorates ethyl carbamate-induced oxidative damage by stimulating AMPK-mediated autophagy[1].
Felodipine-d5 is deuterium labeled Felodipine. Felodipine, a dihydropyridine, is a potent, vasoselective calcium channel antagonist. Felodipine lowers blood pressure (BP) by selective action on vascular smooth muscle, especially in the resistance vessels. Felodipine, an anti-hypertensive agent, induces autophagy. Felodipine can cross the blood-brain barrier[1][2][3].
Lithocholic acid-d4 (3α-Hydroxy-5β-cholanic acid-d4) is the deuterium labeled Lithocholic acid, which is a toxic secondary bile acid[1].
Acetyl-coenzyme A (Acetyl-CoA) is a membrane-impermeant central metabolic intermediate, participates in the TCA cycle and oxidative phosphorylation metabolism. Acetyl-coenzyme A, regulates various cellular mechanisms by providing (sole donor) acetyl groups to target amino acid residues for post-translational acetylation reactions of proteins. Acetyl Coenzyme A is also a key precursor of lipid synthesis[1][2][3][4].
Salbutamol Hemisulfate is a short-acting β2 adrenergic receptor agonistTarget: β2 Adrenergic ReceptorSalbutamol is a short-acting, selective beta2-adrenergic receptor agonist used in the treatment of asthma and COPD. All the effects of R,S-salbutamol on guinea-pig skeletal muscles are due to the activity of the R-enantiomer. Thus there is a common enantiomeric profile for the skeletal muscle and bronchorelaxant activity of the compound [1]. Short-term Salbutamol intake did appear to improve performance during intense submaximal exercise with concomitant increase in substrate availability and utilization, but the exact mechanisms involved need further investigation [2]. Short-term administration of salbutamol increases voluntary muscle strength in man. However, the magnitude and duration of this effect vary between muscle groups. This study implies that the beta 2-adrenoceptor agonists may be of therapeutic potential in altering skeletal muscle function in humans [3].
Olacaftor (VX-440, VX440) is a next-generation CFTR corrector, shows the potential to enhance the amount of CFTR protein at the cell’s surface and for treatment of cystic fibrosis. Fibrosis Phase 2 Clinical
Imipramine is an orally active tertiary amine tricyclic antidepressant. Imipramine is a Fascin1 inhibitor with antitumor activities. Imipramine stimulates U-87MG glioma cells autophagy and induces HL-60 cell apoptosis. Imipramine shows neuroprotective and immunomodulatory effects[1][2][3][4].
3HOI-BA-01 is a mammalian targeting effective rapamycin activation inhibitor.
Entinostat is an oral and selective class I HDAC inhibitor, with IC50s of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3, respectively.
SU9516 is a potent CDK2 inhibitor, with an IC50 of 22 nM, and also shows inhibitory effects on CDK1 and CDK4, with IC50s of 40, 200 nM, respectively.
Paroxetine-d4 (hydrochloride) is deuterium labeled Paroxetine (hydrochloride). Paroxetine hydrochloride is a potent selective serotonin-reuptake inhibitor, commonly prescribed as an and has GRK2 inhibitory ability with IC50 of 14 μM. Paroxetine hydrochloride can be used for the research of depressive disorder[1][2][3].
Dienogest(STS-557) is a specific progesterone receptor agonist with potent oral endometrial activity and is used in the treatment of endometriosis. Target: progesterone receptor agonistDienogest is an orally active synthetic progesterone (or progestin). It is available for use as an oral contraceptive in combination with ethinylestradiol. It has antiandrogenic activity and as a result can improve androgenic symptoms. It is a non-ethinylated progestin which is structurally related to testosterone [1]. Complete sperm suppression was observed in rats sacrificed either 60 or 90 days after dienogest (DNG)+ testosterone undecanoate (TU) administration, for two injections at 45-day interval. The neutral α-glucosidase activity in these treated rats remained in the normal range. Germ cell loss due to apoptosis was frequently observed both after 60 or 90 days of combination treatment. Significant decline in serum gonadotropin and testosterone, both serum and intratesticular levels, were observed in the treated rats. Following stoppage of treatment (given at 45-day interval) after two (0 and 45 days) or three injections (0, 45 and 90 days), complete restoration of spermatogenesis was observed by 120 and 165 days, respectively [2].Clinical indications: Adenomyosis; EndometriosisFDA Approved Date: 1995 Toxicity: weight gain; increased blood pressure; breast tenderness and nausea
Pirarubicin is an anthracycline antibiotics, acts as a topoisomerase II inhibitor, and is a widely used for treatment of various cancers, in particular, solid tumors.
Physalin B, one of the major active steroidal constituents of Cape gooseberry, induces cell cycle arrest and triggers apoptosis in breast cancer cells through modulating p53-dependent apoptotic pathway. Physalin B inhibits the ubiquitin-proteasome pathway and induces incomplete autophagic response in human colon cancer cells in vitro[1][2].
ATG12-ATG3 inhibitor 1 (compound 189) is a potent inhibitor of autophage[1].
UNC2400 is a close analog of UNC1999 with >1,000-fold lower potency than UNC1999 as a negative control for cell-based studies[1][2].
Fenretinide is a synthetic retinoid deriverative, binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death.
LD-ATTEC2, an intermediate, used for lipid metabolism-related diseases study[1].
RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin with MLN0128 (a second-generation mTOR kinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin or mTOR kinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants of mTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1. Anticancer activity[1][2].
GPP78 (CAY10618) is a potent Nampt inhibitor with an IC50 of 3.0 nM for nicotinamide adenine dinucleotide (NAD) depletion. GPP78 is cytotoxic to neuroblastoma cell line SH-SY5Y cells with an IC50 of 3.8 nM by inducing autophagy. GPP78 has anti-cancer and anti-inflammatory effects[1][2].
Daurisoline is a hERG inhibitor and also an autophagy blocker.
Glucosamine sulfate (D-Glucosamine sulfate) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids, is used as a dietary supplement. Glucosamine sulfate also is a natural constituent of glycosaminoglycans in the cartilage matrix and synovial fluid, which when administered exogenously, exerts pharmacological effects on osteoarthritic cartilage and chondrocytes[1].
Zoledronic Acid (Zoledronate) disodium tetrahydrate is a third-generation bisphosphonate (BP), with potent anti-resorptive activity. Zoledronic Acid disodium tetrahydrate inhibits the differentiation and apoptosis of osteoclasts. Zoledronic Acid disodium tetrahydrate also has anti-cancer effects[1].
Carprofen-13C,d3 is the deuterium and 13C labeled Carprofen[1]. Carprofen is a nonsteroid anti-inflammatory agent, acts as a multi-target FAAH/COX inhibitor, with IC50s of 3.9 μM, 22.3 μM and 78.6 μM for COX-2, COX-1 and FAAH, respectively[2][3][4].
Thonningianin B is an antioxidant and an autophagy enhancer[1][2].
Astin B is a orally active and potent cyclic pentapeptide, that can be isolated from Aster tataricus. Astin B has hepatotoxic effects in vitro and in vivo and that hepatic injury was primarily mediated by apoptosis in a mitochondria/caspase-dependent manner. Astin B induces autophagy in L-02 cells, increases LC3-II and decreases p62 expression[1].
Rosuvastatin Sodium is a competitive HMG-CoA reductase (HMGCR) inhibitor, with an IC50 of 11 nM. Rosuvastatin Sodium potently blocks hERG current with an IC50 of 195 nM[2]. Rosuvastatin Sodium reduces the expression of the mature hERG and the interaction of heat shock protein 70 (Hsp70) with the hERG protein. Rosuvastatin Sodium effectively lowers low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein levels[1][2][3].
Aliskiren (CGP 60536; CGP60536B; SPP 100) hydrochloride is an orally active and selective renin inhibitor, with IC50 of 1.5 nM. Aliskiren hydrochloride can be used for the research of hypertension, cardiovascular diseases and cancer cachexia[1]-[4].
Meprednisone is a glucocorticoid and a methylated derivative of prednisone.Target: Glucocorticoid ReceptorMeprednisone is a glucocorticoid and a methylated derivative of prednisone. The methylprednisone to MPL area under the curve ratio decreased from 0.19 +/- 0.04 in control to 0.14 +/- 0.03 in ketoconazole-treated rats (P less than .05) due to altered interconversion between these steroids. An improved pharmacokinetic/dynamic receptor/gene-mediated model characterized the steroid receptor binding and induction of tyrosine aminotransferase activity after i.v. MPL sodium succinate (10 mg/kg). In contrast to previous in vitro studies, ketoconazole at maximally tolerated doses failed to antagonize the steroid receptor-mediated activity of MPL [1].
Oroxylin A is a natural active flavonoid with strong anticancer effects.IC50 value:Target:In vitro: Oroxylin A suppressed the MDM2-mediated degradation of p53 via downregulating MDM2 transcription in wt-p53 cancer cells [1]. Oroxylin A remarkably reduced the generation of lactate and glucose uptake under hypoxia in HepG2 cells, inhibited HIF-1α expression and its stability [2]. Oroxylin A promotes superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA-binding activity of FOXO3a and increases the activity of SOD2 by promoting SIRT3-mediated deacetylation [3]. In vivo: Oroxylin A inhibited the tumor growth of nude mice-inoculated MCF-7 or HCT116 cells. The expression of MDM2 protein in tumor tissue was downregulated by oroxylin A as well [1].