Efflux inhibitor-1 is a pyrazolopyrimidine efflux inhibitor. Efflux inhibitor-1 selectively targets toward ABCG2/BCRP over ABCB1 with IC 50 s of 0.45 μM and 2.17 μM, respectively .

VB124 is an orally active, potent, and selective MCT4 inhibitor, demonstrating specificity in hindering lactate efflux, with IC50 values of 8.6 nM and 19 nM for lactate import and export, respectively, in MDA-MB-231 cells. Its high selectivity for MCT4 over MCT1 positions VB124 as a promising agent for researching cardiac hypertrophy, heart failure, and metabolic disorders [1].

γ-Tocotrienol (Plastochromanol) is one of the four types of tocotrienol, a type of vitamin E. Itl is also a radioprotector, antioxidant. It shows antitumor and antihypertensive effects in vivo.

L-Aspartic aicd sodium (Sodium L-aspartate) is an amino acid, a precursor active molecule for colon-specific active molecule delivery, that promotes Na+ efflux from rat forebrain membrane vesicles.

1. Pseudoprotodioscin has moderate cytotoxicity.

Alisol F 24-acetate is a natural product isolated from Alisma plantago-aquatica Linn[1]. Alisol F 24 Acetate enhances chemosensitivity and apoptosis of MCF-7/DOX Cells by inhibiting P-Glycoprotein-Mediated drug efflux[2].

Adatanserin hydrochloride (WY50324 hydrochloride) is a novel 5-HT(1A)/5-HT(2) receptor ligand with potential neuroprotective effects and inhibition of ischemic efflux of endogenous amino acids, which can be used in the study of depression and anxiety disorders.

CCTA-1523 is an efflux function of ABCG2 inhibitor. CCTA-1523 selectively reverses ABCG2-mediated MDR in cancer cells.

Milataxel is an orally bioavailable taxane with potential antineoplastic activity. Upon oral administration, milataxel and its major active metabolite M-10 bind to and stabilize tubulin, resulting in the inhibition of microtubule depolymerization and cell division, cell cycle arrest in the G2/M phase, and the inhibition of tumor cell proliferation. Unlike other taxane compounds, milataxel appears to be a poor substrate for the multidrug resistance (MDR) membrane-associated P-glycoprotein (P-gp) efflux pump and may be useful for treating multidrug-resistant tumors. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).This compound is unstable in powder form and other related salt forms are recommended.

Thalicarpine is a natural aporphine benzylisoquinoline vinca alkaloid with antineoplastic activity. Thalicarpine binds to and inhibits p-glycoprotein, the multidrug resistance efflux pump. Thalicarpine also induces single-strand breaks in DNA and arrests cancer cells at the G2/M and G1 phase of the cell cycle. Check for active clinical trials or closed clinical trials using this agent.

HTT-D3 is a potent and orally active huntingtin (HTT) splicing modulator. HTT-D3 can lead to HTT mRNA degradation and reduction of HTT levels. HTT-D3 reduces p-glycoprotein (P-gp) efflux, and has research value in Huntington's disease.

Nifedipine (Procardia) is a dihydropyridine calcium channel blocking agent. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

Prazosin hydrochloride (Vasoflex) reduces peripheral resistance and relaxes vascular smooth muscles as a selective adrenergic alpha-1 antagonist by a mechanism not completely known. Prazosin hydrochloride is a synthetic piperazine derivative with hypotensive antiadrenergic properties, It is used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention.

Boeravinone B, a novel efflux pump inhibitor, apart from inhibiting the MdeA mediated efflux, also significantly inhibit the biofilm formation of S. aureus, boeravinone B may be used in combination with mupirocin for further development. Boeravinone B exh

Charybdotoxin-Lq2 (ChTX-Lq2) is a potent inhibitor of calcium-activated potassium efflux, exhibiting a dissociation constant (Kd) of 43 nanomolar (nM) [1].

Pinolenic acid is a polyunsaturated fatty acid found in Korean pine (Pinus orientalis) and maritime pine (Pinus pinaster) seed oils. Both oils have been found to have lipid-lowering properties. A diet containing maritime pine seed oil (MPSO) lowered high-density lipoprotein and ApoA1 levels in transgenic mice expressing human ApoA1. MPSO was found to diminish cholesterol efflux in vitro. Korean pine seed oil supplements may help in obesity by reduction of appetite. People taking this oil had an increase in the satiety hormones CCK and GLP-1 and a reduced desire to eat. The activity of the oil is attributed to pinolenic acid. Pinolenic acid is not converted to arachidonic acid metabolically and can reduce arachidonic acid levels in the phosphatidylinositol fraction of HepG2 cells from 15.9% to 7.0%. Pinolenic acid ethyl ester is a neutral, more lipophilic form of the free acid.

Syringomycin E, an antifungal cyclic lipodepsinonapeptide, inhibits the growth of Saccharomyces cerevisiae by interacting with the plasma membrane. It induces K+ efflux, Ca2+ influx, and alterations in membrane potential, associated with channel formation [1] [2].

NorA-IN-1 is a NorA efflux inhibitor, which can be used to study overcoming multidrug resistance based on microbial efflux transporter proteins.

PD150606 is a selective nonpeptide calpain inhibitor with neuroprotective activity that inhibits μ-calpains and m-calpains. Inhibits erythrocyanine-induced Ca2+ efflux and interferes with excitotoxicity-dependent motor neuron death.

SLUPP-225 is an efflux pump inhibitor (EPI) by interacting with the membrane fusion protein AcrA, a critical component of the AcrAB-TolC efflux pump in Escherichia coli.

Pinolenic acid is a polyunsaturated fatty acid found in Korean pine (Pinus orientalis) and maritime pine (Pinus pinaster) seed oils. Both oils have been found to have lipid-lowering properties. A diet containing maritime pine seed oil (MPSO) lowered HDL and ApoA1 levels in transgenic mice expressing human ApoA1. MPSO was found to diminish cholesterol efflux in vitro.[1] Korean pine seed oil supplements may help in obesity by reduction of appetite. People taking this oil had an increase in the satiety hormones CCK and GLP-1 and a reduced desire to eat.[2] The activity of the oil is attributed to pinolenic acid. Pinolenic acid is not converted to arachidonic acid metabolically and can reduce arachidonic acid levels in the phosphatidylinositol fraction of HepG2 cells from 15.9% to 7.0%.[3]

The KD values of D13-9001 in Escherichia coli and Pseudomonas aeruginosa were 1.15μM and 3.57μM, respectively. D13-9001 has antibiotic activity. It is an effective AcrB (AcrAB-TolC efflux pump subunit) and MexB (MexAB-OprM efflux pump subunit) inhibitor.

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

BODIPY-aminoacetaldehyde diethyl acetal (BAAA-DA) is a stable precursor to BODIPY-aminoacetaldehyde, a cell-permeable fluorescent substrate for aldehyde dehydrogenase (ALDH).1,2BODIPY-aminoacetaldehyde diethyl acetal is converted under acidic conditions to BODIPY-aminoacetaldehyde (BAAA).2BAAA is cell-permeant and is converted intracellularly by ALDH to BODIPY aminoacetate (BAA), which is retained by cells and can be used to identify cells with high ALDH activity.1BAA is a substrate for the efflux pump P-glycoprotein (P-gp) but co-application of BAAA with a P-gp inhibitor, such as verapamil , inhibits BAA efflux.2BAAA-DA has been used to isolate human hematopoietic progenitor cells, which have high ALDH activity, andviaflow cytometry to sort cancer stem cells that contain high levels of ALDH.1,3BAA used in cells can be excited at 488 nm and displays an emission maximum of 512 nm.4 1.Storms, R.W., Trujillo, A.P., Springer, J.B., et al.Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activityProceedings of the National Academy of Sciences of the United States of America96(16)9118-9123(1999) 2.Smith, C.A., Colvin, M., Storms, R.W., et al.BODIPY aminoacetaldehyde diethyl acetal08010501.81-15(2010) 3.Leng, Z., Yang, Z., Li, L., et al.A reliable method for the sorting and identification of ALDHhigh cancer stem cells by flow cytometryExp. Ther. Med.(2017) 4.Pomper, M.G., Wang, H., Minn, I., et al.Red fluorescent aldehyde dehydrogenase (ALDH) substrate(2015)

Iodoantipyrine (Arthripur) is a commonly-used indicator and is used to evaluate in rats by measuring torcular venous efflux after systemic injection of the indicator under conditions of normal and high CBF.

Bonducellin has anti-inflammatory activities, it can significantly and dose-dependently inhibit the inflammatory mediators; nitric oxide (NO), and cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-12. Bonducellin shows weak antimalarial ac

Gangliotetraose (Gg4), a tetrasccharide, predominantly comprises GM1 and its sialylated derivatives, which play a crucial role in modulating nuclear Ca2+ efflux and maintaining lower nuclear Ca2+ levels in differentiated neurons. Moreover, GM1 influences neuronal plasticity, repair mechanisms, and neurotrophin release in the brain [1] [2].

MRL-494 is an antibacterial agent and is a small-molecule inhibitor of β-barrel assembly machine A (BamA) impervious to efflux and the outer membrane permeability barrier.

Benzquinamide (P2647), an antiemetic agent with anticancer activity, inhibits p-glycoprotein-mediated drug efflux and potentiates the cytotoxicity of anticancer drugs in multidrug-resistant cells.The Ki values of Benzquinamide for α2A, α2B, and α2C adrenergic receptor (α2-AR) were 1,365, 691, and 545 nM, respectively. 545 nM, respectively.

C2 Adamantanyl globotriaosylceramide (AdaGb3) is a bioactive sphingolipid and water-soluble form of globotriaosylceramide that contains an adamantanyl group in place of the fatty acyl chain. It inhibits Vero toxin binding to globotriaosylceramide in an ELISA assay when used at a concentration of 10 μM. AdaGb3 decreases cell surface expression of P-glycoprotein (P-gp) and reduces efflux of rhodamine 123 in MDCK cells. It also increases apical-to-basal transport of vinblastine in human intestinal C2BBe1 cells.

E17110 is an LXRβ agonist. E17110 exhibited a significant activation effect on LXRβ (EC50: 0.72 μmol/L). E17110 also increased the expression of ABCA1 and ABCG1 in RAW264.7 macrophages. E17110 significantly decreased cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages.

Cajanin has potential hypolipidemic effects,possibly via up-regulating the ABCA1 protein expression,subsequently resulting in increased macrophage cholesterol efflux and RCT, it can significantly improve basal glucose uptake in HepG2 cells, its improving effect is concentration dependent, it exhibits effects stronger than that of rosiglitazone, which has been used as an antidiabetic drug.

Tetrathiomolybdate (TM) promotes the dimerization of the metal-binding domain (WLN4) of the cellular copper efflux protein ATP7B through its characteristic sulfur bridge Mo2S6O2 cluster, and is used in the clinical treatment of Wilson’s disease.

RG33 Peptide, utilized in type 2 diabetes (T2D) research [1], enhances glucose clearance in insulin-resistant mice and facilitates cholesterol efflux in cultured macrophages by effectively solubilizing lipid vesicles.

Efflux pump-IN-3, an AcrB efflux pump inhibitor, potentiates the effect of antibiotics by inhibiting the efflux of Nile Red (a known substrate of AcrB). It does not disrupt the bacterial outer membrane or exhibit toxicity in a nematode model [1].

Efflux pump-IN-2 is an AcrB efflux pump inhibitor, with ability to potentiate the effect of antibiotics . Efflux pump-IN-2 inhibits Nile Red (a known substrate of AcrB) efflux. Efflux pump-IN-2 does not disrupts the bacterial outer membrane nor display toxicity in a nematode model [1] .

Efflux pump-IN-4, an AcrB efflux pump inhibitor, potentiate[s] the effects of antibiotics by inhibiting the efflux of Nile Red (a known substrate of AcrB). It does not disrupt the bacterial outer membrane or display toxicity in a nematode model [1].

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).

timcodar is a non-FKBP12 binding macrolide derivative that is an efflux pump inhibitor with antimicrobial activity, inhibition of lipid accumulation, inhibition of Mycobacterium tuberculosis, and can be used in the study of obesity. timcodar is a non-FKBP12 binding macrolide derivative with antimicrobial activity.

NP-313 (NSC-4264) is a potent antithrombotic agent that inhibits platelet aggregation and activation by inhibiting thromboxane A 2 synthesis and selectively inhibiting SOCC-mediated Ca2+ efflux.

BDM91270 (compound 29) serves as an inhibitor of the E. coli AcrAB-TolC efflux pump, displaying an EC90 value of 0.6 μM against wild-type E. coli AcrB. It has applications in research on Escherichia coli drug resistance [1].

Sarglaroids F (compound 6), an anti-inflammatory agent extracted from the roots of Grass Coral, suppresses LPS/ATP-induced IL-1β secretion by modulating K+ efflux and diminishing Caspase-1(P20) concentrations. Additionally, Sarglaroids F exhibits no cytotoxic effects on RAW264.7 cells [1].

RG33, a synthetic 33-amino acid peptide, matches the sequence of amino acids 209-219 and 220-241 found in the C-terminal domain class Y helices of apolipoprotein A1 (ApoA1). This compound has the ability to solubilize multilamellar vesicles (MLVs) containing 1,2-dimyristoyl-sn-glycero-3-PC (DMPC), resulting in the formation of recombinant HDL. When bound to lipids, RG33 facilitates cholesterol efflux in J774 macrophages and has been shown to reduce blood glucose levels in insulin-resistant mice at a dosage of 12 mg/kg.

Thyminose induces apoptosis by inhibiting glutathione synthesis and increasing its efflux.

6,8-Diprenylnaringenin (Senegalensin) is a natural product from hop Humulus lupulus. 6,8-Diprenylnaringenin is a breast cancer resistance protein(BCRP) inhibitor with some estrogenicity.

PF-06273340 is an effective, Selective, and Peripherally Restricted Pan-Trk inhibitor (IC50: Trk-A = 6 nM; Trk-B = 4 nM; Trk-C = 3 nM). PF-06273340 has low metabolic turnover in HLM and hHep is a good substrate for efflux transporters P-gp (ER = 35.7) and BCRP (ER = 4.0) and has moderate passive permeability (RRCK Papp = 5.4 × 10 6 cm s 1).

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.

Ritodrine hydrochloride (NSC 291565) binds to and activates beta-2 adrenergic receptors of myometrial cells in the uterus, which decreases the intensity and frequency of uterine contractions. Ritodrine hydrochloride (NSC 291565) is a phenethylamine derivative with tocolytic activity. Specifically, Ritodrine hydrochloride (NSC 291565) probably activates adenyl cyclase, thereby increasing production of cyclic adenosine monophosphate (cAMP), which in turn enhances the efflux of calcium from vascular smooth muscle cells. A lack of intracellular calcium prevents uterine myometrial contractions. In addition, this agent may directly inactivate myosin light chain kinase, a critical enzyme necessary for the initiation of muscle contractions.

Phenytoin (5,5-Diphenylhydantoin) is a hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses. The reduction of potentiation prevents cortical seizure foci spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce sensitivity of muscle spindles to stretch causing muscle relaxation.