efflux activity

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.

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.

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.

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.

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.

Phenytoin (5,5-Diphenylhydantoin) is a hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. It potentially acts by promoting sodium efflux from neurons in the motor cortex, reducing post-tetanic potentiation at synapses. This prevents cortical seizure foci from spreading to adjacent areas and stabilizes the threshold against hyperexcitability. Additionally, it appears to reduce muscle spindle sensitivity to stretch, causing muscle relaxation.

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.

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.

Tariquidar methanesulfonate hydrate (XR9576 methanesulfonate hydrate) is a selective and potent P-glycoprotein drug efflux pump inhibitor with potential anticancer activity that induces P-glycoprotein inhibition of the blood-brain barrier in rats.

A-839977 is a selective P2X7 receptor antagonist with anti-inflammatory and analgesic properties, inhibiting BzATP-induced calcium efflux from the P2X7 receptor, and is used in the study of renal fibrosis.

Antibiofilm agent-12 (Compound C13), an antifungal belonging to the carbamate derivatives, exhibits significant antifungal activity against Candida auris, with an MIC90 of 237.9 μM. It inhibits the drug efflux pump activity of Candida auris and promotes ergosterol depletion, thereby hindering the formation of Candida auris biofilms and reducing its metabolic flexibility. Additionally, Antibiofilm agent-12 demonstrates antifungal efficacy in a C. elegans model following Candida auris infection.

Multi-target kinase inhibitor 4 (Compound 2) is a PI3K/DNA-PK inhibitor and a potent chemosensitizer that enhances the number of DNA double-strand breaks induced by Doxorubicin. It serves as an effective multidrug resistance (MDR) inhibitor, demonstrating inhibitory activity against P-glycoprotein (P-gp) mediated drug efflux. Multi-target kinase inhibitor 4 can be encapsulated in PEG-coated lipid nanoparticles.

NorA-IN-2 (compound DZ-3) is a potent inhibitor of NorA. It exhibits activity as a NorA efflux pump inhibitor (EPI).

IITR08367 is a potent inhibitor of the efflux pump Acinetobacter baumannii Fosfomycin Efflux pump (AbaF), designed to enhance the antibacterial activity of Fosfomycin against Acinetobacter baumannii. It operates by disrupting the Fosfomycin/H+ antiport activity.

P-gp modulator-4 (compound 4c) inhibits the efflux function of P-glycoprotein (P-gp). This compound demonstrates multidrug resistance (MDR) reversal activity in cancer, with an IC50 for Paclitaxel of 8.80 and a reversal fold of 211.8.

Antitrypanosomal agent 24 is a benzothiazole amidoxime compound with potent and selective activity against trypanosomes (IC50 = 0.92 μM). It serves as a substrate for the P-glycoprotein efflux pump and exhibits high membrane permeability and good metabolic stability. Antitrypanosomal agent 24 binds to DNA/RNA via intercalation.

VEGFR-2/P-gp-IN-1 is a derivative of Licochalcone A, functioning as an orally active inhibitor of VEGFR-2 (IC50= 0.885 μM) and P-glycoprotein (P-gp). It combats tumor proliferation and overcomes chemotherapy resistance by simultaneously inhibiting VEGFR-2 kinase activity and the P-gp drug efflux pump. This compound suppresses the phosphorylation of VEGFR-2 and proteins in the downstream PI3K/AKT signaling pathway, induces apoptosis, arrests cells in the S phase, and inhibits invasive migration. Additionally, VEGFR-2/P-gp-IN-1 demonstrates potent in vivo antitumor activity in HeLa/DDP cell xenograft models and is applicable in cervical cancer research.

ARN25657 is a dual regulator of D3R/GSK-3β. It demonstrates partial agonist activity at the D3 receptor (EC50 = 15.2 nM, Ki = 1.5 nM) alongside potent inhibitor activity against GSK-3β (IC50 = 19.3 nM). ARN25657 shows excellent GSK-3β selectivity over FYN, PKA, and CDK5/p35. It inhibits P-gp-mediated efflux of acetoxymethyl calcein, enhancing in vitro ADME properties while maintaining balanced dual-target distribution. ARN25657 is applicable in the study of bipolar disorder and related neuropsychiatric conditions.

P-gp-IN-32 is a P-glycoprotein (P-gp) inhibitor with low cytotoxicity, demonstrating significant multidrug resistance (MDR) reversal activity against doxorubicin in MCF7/ADR cells. It has an IC50 value of 0.11 μM and a resistance reversal factor (RF) of 215.9. P-gp-IN-32 interacts directly with P-gp, inducing conformational changes and inhibiting its efflux function. This compound is applicable in cancer research, including studies on breast cancer.

FabX-IN-1 (Compound 47) is a selective FabX inhibitor with an IC50 of 0.128 μM. It exhibits narrow-spectrum antibacterial activity against Helicobacter pylori, with an MIC of 64 μg/mL. Its synergistic inhibitory effect is significantly enhanced when used in combination with membrane-permeabilizing agents, efflux pump inhibitors, and Clarithromycin. FabX-IN-1 is applicable for bacterial infection research.

Tubulin polymerization/P-gp-IN-1 is a dual inhibitor targeting both tubulin polymerization and P-gp. It disrupts tubulin polymerization, inducing G2/M phase arrest and apoptosis (apoptosis). By inhibiting P-gp's efflux function, it reverses multidrug resistance (MDR). Tubulin polymerization/P-gp-IN-1 has dual roles: direct antitumor activity and reversal of P-gp-mediated cisplatin resistance. It binds stably to the tubulin CBS domain (ΔG = −12.4 kcal/mol) and the P-gp hydrophobic cavity (ΔG = −10.8 kcal/mol). Tubulin polymerization/P-gp-IN-1 is applicable for research on drug-resistant cervical cancer.

Antibacterialagent 309 (Compound C9) is an antibacterial agent that serves as a substrate for the AcrB efflux pump. It promotes the polymerization of FtsZ and exhibits antibacterial activity against erythromycin-resistant S. pyogenes2 (MIC = 0.25 μg/mL), penicillin-resistant S. aureusCI (MIC = 0.125 μg/mL), and penicillin-resistant S. epidermidis (MIC = 2 μg/mL). However, it shows weak antibacterial activity against wild-type E. coli BW25113 (MIC = 256 μg/mL).

LP07 is an antibacterial agent targeting Pseudomonas aeruginosa. It exhibits a minimum inhibitory concentration (MIC) of 8 μg/mL against both wild-type and efflux pump-deficient strains of P. aeruginosa PA14. LP07 exerts its antibacterial effects by directly disrupting the structural integrity of bacterial cell membranes. It shows moderate inhibition of MMP-17 and MMP-19 but has no significant inhibitory effect on other MMP subtypes. LP07 does not inhibit LpxC enzyme activity and can be utilized in research on Pseudomonas aeruginosa infections.

Axl-IN-21 is an orally bioavailable selective AXL inhibitor with a Kd of 2.7 nM and an IC50 of 4.0 nM. It demonstrates strong inhibitory activity against various cancer-related kinases while maintaining kinase selectivity, including Mer (Kd = 1.4 nM), DDR1 (IC50 = 22.2 nM), HIPK4 (Kd = 11.0 nM), and LOK (Kd = 10 nM). By blocking the AXL/STAT3/ABCG1 signaling pathway induced by GAS6 from tumor-associated fibroblasts, Axl-IN-21 can overcome tumor microenvironment-driven resistance, restore chemotherapy sensitivity, and inhibit drug efflux. In MDA-MB-231 cells, it inhibits TGF-β1-induced epithelial-mesenchymal transition, cell migration, and invasion. Axl-IN-21 exhibits no significant toxicity to non-cancer cells and is relevant for research in triple-negative breast cancer and gastric cancer.