Ruxolitinib phosphate is a potent JAK1/2 inhibitor with IC50s of 3.3 nM/2.8 nM, respectively, showing more than 130-fold selectivity over JAK3.
(Rac)-Sitagliptin is an isoform of Sitagliptin (HY-13749), which is a potent and orally active inhibitor of DPP4 with an IC50 of 19 nM in Caco-2 cell extracts[1].
Oxyresveratrol is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. It effectively scavenges H2O2, NO (IC50 = 45.3 μM), and the artificial free radical 2,2-diphenyl-l-picrylhydrazyl (IC50 = 28.9 μM) In vitro: 1)oxyresveratrol exhibited more than 50% inhibition at 100 μM on L-tyrosine oxidation by murine tyrosinase activity.2) oxyresveratrol showed an IC50 value of 52.7 μM on the enzyme activity. 3) oxyresveratrol works through reversible inhibition of tyrosinase activity rather than suppression of the expression and synthesis of the enzyme.[2] In vivo: 1) Oxyresveratrol (10 or 20 mg/kg) significantly reduced the brain infarct volume by approximately 54% and 63%, respectively, when compared to vehicle-treated MCAO rats.2) oxyresveratrol treatment diminished cytochrome c release and decreasedcaspase-3 activation in MCAO rats. [3]
Lithocholic acid-d5 is deuterium labeled Lithocholic acid.
PF-06447475 trihydrochloride is a highly potent, selective, brain penetrant LRRK2 kinase inhibitor with IC50 values of 3 nM and 11 nM for WT LRRK and G2019S LRRK2, respectively. PF-06447475 trihydrochloride can be used for parkinson's disease (PD) research[1].
Emetine dihydrochloride hydrate is an anti-protozoal drug previously used for intestinal and tissue amoebiasis.
Alisertib (MLN 8237) sodium is an orally active and selective Aurora A kinase inhibitor (IC50=1.2 nM), which binds to Aurora A kinase resulting in mitotic spindle abnormalities, mitotic accumulation. Alisertib sodium induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells. Antitumor activity[1][2][3].
Bexarotene D4 is a deuterium labeled Bexarotene (LGD1069). Bexarotene (LGD1069) is a selective retinoid X receptors (RXR) agonist for the treatment of cutaneous T-cell lymphoma[1][2][3][4][5].
Esmolol-d7 hydrochloride is the deuterium labeled Esmolol hydrochloride. Esmolol hydrochloride is a beta adrenergic receptor blocker[1][2].
Proflavine hemisulfate is an Acridine derivative, which is a slow-acting disinfectant with bacteriostatic action against many Gram-positive bacteria but less effective against Gram-negative organisms.
Mefloquine hydrochloride is a quinoline antimalarial drug that is structurally related to the antiarrhythmic agent quinidine. IC50 Value: 1 microM ( for K+ channel) [1]Target: AntiparasiticMefloquine is widely used in both the treatment and prophylaxis of Plasmodium falciparum malaria. MQ can induces oxidative stress in vitro. Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells [2].in vitro: Mefloquine inhibitedKvLQT1/minK channel currents with an IC50 value of approximately 1 microM. Mefloquine slowed the activation rate of KvLQT1/minK and more block was evident at lower membrane potentials compared with higher ones. HERG channel currents were about 6-fold less sensitive to block by mefloquine (IC50 = 5.6 microM). Block of HERG displayed a positive voltage dependence with maximal inhibition obtained at more depolarized potentials [1]. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. MQ-mediated ROS simultaneously downregulated Akt phosphorylation and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and adenosine monophosphate-activated protein kinase (AMPK) signaling in PC3 cells [2]. in vivo: Pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9-11 post coitum (pc). The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated [3].Clinical trial: Activity of Mefloquine Against Urinary Schistosomiasis . Phase 2
Venetoclax-d8 is deuterium labeled Venetoclax. Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a Ki of less than 0.01 nM. Venetoclax induces autophagy[1][2][3].
CHIR-99021 monohydrochloride is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; > 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases.
Memantine-d6 hydrochloride is the deuterium labeled Memantine hydrochloride. Memantine (hydrochloride) (D-145 (hydrochloride)) is a moderate affinity, uncompetitive NMDA receptor antagonist, inhibit CYP2B6 and CYP2D6 with Ki of 0.51 nM and 94.9 μM, respectively[1].
Hoechst 33342 is a DNA minor groove binder used fluorochrome for visualizing cellular DNA.
Cycloheximide (Naramycin A) is an eukaryote protein synthesis inhibitor, with IC50s of 532.5 nM and 2880 nM for protein synthesis and RNA synthesis in vivo, respectively.
Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia[1].
Isradipine-d3 (PN 200-110-d3) is the deuterium labeled Isradipine. Isradipine (PN 200-110) is an orally active L-type calcium channel blocker. Isradipine, as a powerful peripheral vasodilator, is a dihydropyridine calcium antagonist with selective actions on the heart as well as the peripheral circulation. Isradipine is a potentially viable neuroprotective agent for Parkinson's disease[1][2][3].
Ursolic acid(Bungeolic acid) is a natural pentacyclic triterpenoid carboxylic acid, exerts anti-tumor effects and is an effective compound for cancer prevention and therapy. IC50 value:Target:in vitro: UA induced phosphorylation of AMP-activated protein kinase alpha (AMPKα) and suppressed the protein expression of DNA methyltransferase 1 (DNMT1) in the dose-dependent manner [1]. The combination of ursolic acid (0.5 μM) and leucine (10 μM) proved to be the most effective in promoting myogenic differentiation. The combination of ursolic acid and leucine significantly increased CK activity than treatment with either agent alone. The level of myosin heavy chain, a myogenic differentiation marker protein, was also enhanced by the combination of ursolic acid and leucine [2]. Ursolic acid efficiently induced apoptosis, possibly via the downregulation of B-cell lymphoma 2 (Bcl-2), the upregulation of Bcl-2-associated X protein and the proteolytic activation of caspase-3. Furthermore, the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was increased by the administration of ursolic acid. In addition, ursolic acid significantly suppressed the invasive phenotype of the SNU-484 cells and significantly decreased the expression of matrix metalloproteinase (MMP)-2 [3]. ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis [4].in vivo: UA treatment markedly improved the survival of septic rats, and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, infiltration of leukocytes and proteins, myeloperoxidase activity, and malondialdehyde content. In addition, UA significantly decreased the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lung, which are involved in the productions of nitric oxide and prostaglandin E2 [5].
Piperine, a natural alkaloid isolated from Piper nigrum L, inhibits P-glycoprotein and CYP3A4 activities with an IC50 value of 61.94±0.054 μg/mL in HeLa cell.
Dihydromyricetin is a potent inhibitor with an IC50 of 48 μM on dihydropyrimidinase. Dihydromyricetin can activate autophagy through inhibiting mTOR signaling. Dihydromyricetin suppresses the formation of mTOR complexes (mTORC1/2).
Pennogenin 3-O-beta-chacotrioside is an active component isolated from Paris polyphylla, modulates autophagy via increasing the expressions of autophagy-related proteins LC3 and Beclin-1. Anti-colorectal cancer activity[1].
Pirarubicin Hydrochloride is an anthracycline antibiotics, acts as a topoisomerase II inhibitor, and is a widely used for treatment of various cancers, in particular, solid tumors.
Sapanisertib (INK-128) is a ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase.
Di-N-desethyl Amiodarone hydrochloride is a metabolite of Amiodarone (HY-14187). Di-N-desethyl Amiodarone hydrochloride is a strong inhibitor of the respiratory chain[1].
JPH203 Dihydrochloride is a tyrosine analog, acts as a selective inhibitor of L-type amino acid transporter 1 (LAT1), and is used in cancer research.
A small molecule autophagy enhancer that specificly inhibits myotubularin-related phosphatase MTMR14; at concentrations of 2, 10, and 100 uM, AUTEN-67 inhibits MTMR14 by nearly 3%, 25%, and 70%, respectively; shows no activity for CDC25B , other phosphatase, PTPN1; significantly increases autophagic flux in cell lines and in vivo models, promotes longevity and protects neurons from undergoing stress-induced cell death; also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects.
Demethoxycurcumin(Curcumin II) is a major active curcuminoid; possess anti-inflammatory properties; also exert cytotoxic effects in human cancer cells via induction of apoptosis.IC50 value: Target:in vitro: DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway [1]. BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively [2]. Genes associated with DNA damage and repair, cell-cycle check point and apoptosis could be altered by DMC; in particular, 144 genes were found up-regulated and 179 genes down-regulated in NCI-H460 cells after exposure to DMC [3]. in vivo: At low doses, both the curcuminoid mixture and curcumin I did not affect brain stimulation reward, whereas, higher doses increased ICSS thresholds. Curcumin II and curcumin III did not affect brain stimulation reward at any doses. Subthreshold doses of the curcuminoid mixture and curcumin I inhibited the reward-facilitating effect of morphine.
Vandetanib hydrochloride is a potent inhibitor of VEGFR2 with IC50 of 40 nM.
Pramipexole 2Hcl is a partial/full D2S, D2L, D3, D4 receptor agonist with a Ki of 3.9, 2.2, 0.5 and 5.1 nM for D2S, D2L, D3, D4 receptor, respectively. IC50 Value: 3.9 nM(D2S); 2.2 nM(D2L); 0.5 nM(D3); 5.1 nM(D4)Target: Dopamine ReceptorPramipexole dihydrochloride is a dopamine receptor agonist with selectivity for the D3 receptor (Ki values are 3.9, 3.3, 0.5 and 3.9 nM for D2L, D2S, D3 and D4 receptors respectively). Pramipexole dihydrochloride exhibits negligable affinity for D1 and D5 receptors. Pramipexole has been found to have neuroprotective effects independent of its dopamine receptor agonism. It reduces mitochondrial reactive oxygen species (ROS) production and inhibits the activation of apoptotic pathways. Pramipexole displays activity in the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS).