pumps

Norverapamil hydrochloride (D591 hydrochloride) ((±)-Norverapamil hydrochloride) is an N-demethylated metabolite of Verapamil and it is an L-type calcium channel blocker and a P-glycoprotein (P-gp) function inhibitor.

CALP3 acetate is a potent Ca2+ channel blocker that activates EF hand motifs of Ca2+-binding proteins. CALP3 acetate can functionally mimic increased [Ca2+]i by modulating the activity of Calmodulin (CaM), Ca2+ channels and pumps.

Annonacin is an acetogenin that promotes cytotoxicity by inhibiting the mitochondrial complex and acts as the active agent in Graviola leaf extract, inhibiting sodium/potassium (NKA) and sarcoplasmic reticulum (SERCA) ATPase pumps[1].

Levolansoprazole ((S)-Lansoprazole), a proton pump inhibitor, irreversibly inhibits H+/K+-stimulated ATPase pumps in parietal cells (IC50: 5.2 μM). It also inhibits acid formation in isolated canine parietal cells (IC50: 82 μM). Both (R)- and (S)-lansoprazole are pharmacologically active with similar potencies.

ATP-PEG8-Biotin is an ATP-binding PEG linker. ATP is a fundamental component for energy storage and metabolism within the body, providing metabolic energy to operate pumps and functioning as a coenzyme in cells. Additionally, it serves as a significant endogenous signal molecule in immune responses and inflammation.

c-Met-IN-23 (Compound 12g) functions as a c-Met inhibitor with an IC50 of 0.052 μM against c-Met. It also inhibits the MDR1 and MRP1/2 pumps in cancerous HepG2 and BxPC3 cells. As such, c-Met-IN-23 serves as an anticancer agent.

DJ101is an effective and metabolically stable inhibitor of tubulin. It can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors.

Bromotetrandrine is an P-glycoprotein inhibitor, which were developed and coadministered with chemotherapeutic drugs to overcome the effect of efflux pumps thus enhancing the chemosensitivity of therapeutics.

Milbemycin A4 oxime, a derivative of milbemycin A4 and a component of milbemycin oxime, exhibits insecticidal and nematocidal activity. At 0.05 mg/kg, it reduces microfilariae of the heartworm D. immitis in naturally infested dogs and inhibits the growth of C. glabrata clinical isolates with MIC80 values of 16 to >32 μg/ml. At 2.5 μg/ml, it blocks fluconazole efflux from C. glabrata clinical isolates (but not from strains lacking CgCDR1 and PDH1 efflux pumps) and reduces MICs of fluconazole and 4-nitroquinoline 1-oxide in wild-type C. glabrata. Furthermore, it enhances adriamycin-induced inhibition of cell growth, increases intracellular accumulation of adriamycin and the P-glycoprotein substrate rhodamine 123 in adriamycin-resistant, but not adriamycin-sensitive, MCF-7 breast cancer cells in a concentration-dependent manner.

Ultrapotent PSEM (uPSEM) agonist for PSAM4-GlyR and PSAM4-5HT3 (Ki = 0.7 nM for PSAM4-GlyR and <10 nM for PSAM4-5HT3). Exhibits >10,000-fold agonist selectivity for PSAM4-GlyR over α7-GlyR, α7-5HT3, and 5HT3-R, and 230-fold selectivity over α4β2 nAChR. Also weak partial agonist (~10 %) at α4β2 nAChR. Retains the potency of varenicline (Cat.No. 3754) for PSAM4-GlyR with enhanced chemogenetic selectivity. Does not act as a substrate for P-glycoprotein pumps. Silences neurons in vivo. Brain-penetrant. Magnus et al (2019) Ultrapotent chemogenetics for research and potential clinical applications. Science doi: 10.1126/science PMID:30872534

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). Regulation of bacterial quorum sensing signaling systems to inhibit pathogenesis represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[3] AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group), and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[4] C16-HSL is one of a number of lipophilic, long acyl side-chain bearing AHLs, including its monounsaturated analog C16:1-(L)-HSL, produced by the LuxI AHL synthase homolog SinI involved in quorum-sensing signaling in S. meliloti, a nitrogen-fixing bacterial symbiont of certain legumes.[5],[6] C16-HSL is the most abundant AHL produced by the proteobacterium R. capsulatus and activates genetic exchange between R. capsulatus cells.[7] N-Hexadecanoyl-L-homoserine lactone and other hydrophobic AHLs tend to localize in relatively lipophilic cellular environments of bacteria and cannot diffuse freely through the cell membrane. The long-chain N-acylhomoserine lactones may be exported from cells by efflux pumps or may be transported between communicating cells by way of extracellular outer membrane vesicles.[8],[9]Reference:[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry Journal of Bacteriology 188(2), 773-783 (2006).[3]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies Nature Reviews.Microbiology 6(1), 17-27 (2008).[4]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions FEBS Letters 580, 561-567 (2006).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium Archives of Microbiology 180, 494-497 (2003).[7]. Schaefer, A.L., Taylor, T.A., Beatty, J.T., et al. Long-chain acyl-homoserine lactone quorum-sensing regulation of Rhodobacter capsulatus gene transfer agent production Journal of Bacteriology 184(23), 6515-6521 (2002).[8]. Pearson, J.P., Van Delden, C., and Iglewski, B.H. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals Journal of Bacteriology 181(4), 1203-1210 (1999).[9]. Mashburn-Warren, L., and Whiteley, M. Special delivery: Vesicle trafficking in prokaryotes Molecular Microbiology 61(4), 839-846 (2006).

C18-HSL is one of four lipophilic, long acyl side-chain-bearing N-acylated homoserine lactones (AHLs) produced by the LuxI AHL synthase homolog SinI, involved in quorum sensing signaling in S. meliloti, a nitrogen-fixing bacterial symbiont of the legume [M. sativa]. C18-HSL and other hydrophobic AHLs tend to localize in relatively lipophilic cellular environments and cannot diffuse freely through the cell membrane. These long-chain N-acylhomoserine lactones may be exported from cells by efflux pumps or transported between communicating cells via extracellular outer membrane vesicles. Quorum sensing, a regulatory system used by bacteria to control gene expression in response to cell density, manifests in phenotypes such as biofilm formation and virulence factor production. Coordinated gene expression is achieved through the production, release, and detection of small diffusible signal molecules called autoinducers, including AHLs, which vary in acyl group length (C4-C18), C3 substitution (hydrogen, hydroxyl, or oxo group), and the presence or absence of carbon-carbon double bonds, conferring signal specificity through LuxR family transcriptional regulators. Regulation of bacterial quorum sensing signaling to inhibit pathogenesis represents a novel approach to antimicrobial therapy in treating infectious diseases.

ATP dipotassium (Adenosine 5'-triphosphate dipotassium) is a vital compound involved in energy storage and metabolism within living organisms, supplying metabolic energy for driving pumps and acting as a coenzyme in cellular processes, while also functioning as a significant endogenous signaling molecule contributing to immunity and inflammation.

4SC-207 is a novel microtubule inhibitor , which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. 4SC-207 may be a potential anti-cancer agent.

ATP ditromethamine (Adenosine 5'-triphosphate ditromethamine) is a vital in vivo energy storage and metabolic constituent that fuels metabolic pumps and acts as a cellular coenzyme. It also plays a crucial role as an endogenous signaling molecule in immunity and inflammation [1] [2].

Caloxin 3A1, a biologically active peptide, is a member of the caloxins, which are inhibitors of the extracellular plasma membrane (PM) Ca2+ pumps. Specifically, it inhibits plasma membrane calcium pumps (PMCAs) without affecting the sarcoplasmic reticulum Ca2+ pump, nor does it inhibit the formation of the acylphosphate intermediate from ATP.

Timcodar mesylate (VX-853-2) and its analog VX-710 function as inhibitors of mammalian multidrug-resistant bacterial efflux pumps, specifically blocking the efflux of ethidium bromide in Staphylococcus aureus. This capability suggests that Timcodar mesylate may boost the efficacy of antibiotics by impeding the bacterial efflux pumps, therefore lowering the minimum inhibitory concentrations of certain antibiotics against Gram-positive pathogens including Staphylococcus aureus, Enterococcus, and Streptococcus pneumoniae.

P-gp Modulator-5 (compound 25) serves as a modulator of P-gp, effectively inhibiting the proliferation of multidrug-resistant (MDR) tumors. This compound suppresses the function of drug efflux pumps in MDR cells, which results in significant accumulation of ROS and modifications in cell cycle profiles.

Levolansoprazole-d4 is a deuterated compound of Levolansoprazole. Levolansoprazole has a CAS number of 138530-95-7. Levolansoprazole, a proton pump inhibitor, irreversibly inhibits H+/K+-stimulated ATPase pumps in parietal cells (IC50: 5.2 µM). It also inhibits acid formation in isolated canine parietal cells (IC50: 82 µM). Both (R)- and (S)-lansoprazole are pharmacologically active with similar potencies.

Volkensiflavone (Talbotaflavone) is a natural product found in astragalus and garcinia. It has the function of plant metabolite, is a secondary metabolic product. Volkensiflavone is a biflavonoid belonging to the hydroxyl and oxyflavone groups. Volkensiflavone can be used as an adjuvant in the antibiotic treatment of multidrug-resistant Staphylococcus aureus that overexpresses efflux pumps.

CALP3 TFA is a potent Ca2+ channel blocker that activates EF-hand motifs of Ca2+-binding proteins. It can functionally mimic increased [Ca2+]i by modulating the activity of Calmodulin, Ca2+ channels, and pumps.

Cerium oxide, 99.99% metals basis, <5 μm, functions as a biochemical analysis reagent with anti-inflammatory properties and mimics the activity of SOD and catalase. It is applicable in treating chronic inflammation and is utilized in industrial applications such as solid oxide fuel cells, solar cells, catalysts, oxygen pumps, and gas sensors.