drug-resistance

Inz-1 is an effective and fungal-selective inhibitor of mitochondrial cytochrome bc1 with IC50s of 8.092 and 45.320 μM for yeast and human. Inz-1 reverses Fluconazole or other triazole antifungals' resistance in the pathogenic fungus Candida albicans.

CASIN (Pirl1-related Compound 2) is a specific inhibitor of GTPase Cdc42 (IC50: 2 uM).

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

ROCK2-IN-10 is an effective ROCK inhibitor, which is widely used in the research fields of cell migration, invasion, differentiation, proliferation, immune response, drug resistance, cytoskeletal dynamics, etc.

Ethamsylate (Dicynene) usually is used as a hemostatic drug, which increases capillary endothelial resistance and platelet adhesion, and inhibits biosynthesis and action of prostaglandins.

Amiodarone hydrochloride is an anti-anginal agent and a class III antiarrhythmic drug that inhibits potassium channels (including wild-type hERG channels and their tail currents, with an IC₅₀ of approximately 45 nM) as well as voltage-gated sodium channels. This leads to prolonged action potential duration in ventricular and atrial myocytes, resulting in reduced heart rate and vascular resistance. It activates ERK1/2 and p38 MAPK signaling pathways in fibroblasts, promoting cell proliferation and myofibroblast differentiation. Amiodarone hydrochloride is widely used in the study of supraventricular and ventricular arrhythmias and can also be used to establish pulmonary fibrosis animal models.

Tenofovir (GS 1278) is an adenine analog REVERSE TRANSC-RIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B. It is used to treat HIV INFECTIONS and CHRONIC HEPATITIS B, in combination with other ANTIVIRAL AGENTS, due to the emergence of ANTIVIRAL DRUG RESISTANCE when it is used alone.

Darunavir (TMC114) is an HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.

Darunavir Ethanolate (UIC 94017) is an HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.

Cyclohexane-1,2,3,4,5,6-hexaol, also known as inositol, is a natural cyclohexane derivative and alcohol compound with biological activity in signal transduction, osmotic pressure regulation, and lipid metabolism, and is widely used in biochemical experiments and drug synthesis research.

EFdA-TP 3TEA is the salt form of EFdA-TP.EFdA-TP 3TEA is a nucleoside analog that is a novel, potent, and selective nucleoside reverse transcriptase (RT) inhibitor that inhibits HIV-1 reverse transcriptase by multiple mechanisms, thereby increasing its drug resistance.

Duocarmycin GA, an antibody drug conjugate (ADC) toxin and a DNA alkylating agent, effectively targets and binds in the minor groove of DNA. It is particularly potent against multi-drug resistant cell lines, offering a strategic approach in combating resistance.

Hsp90-Cdc37-IN-1 is an Hsp90-Cdc37 interaction disruptor (IC50: 140 nM) that inhibits cell migration and reverses drug resistance.

CH-0793076, a hexacyclic camptothecin analog, is an active drug and major metabolite of TP300. CH-0793076 is efficacious against cells expressing BCRP (breast cancer resistance protein). CH-0793076 inhibits DNA topoisomerase I (IC50: 2.3 μM).

Inz-5 is a fungal-selective inhibitor of mitochondrial cytochrome bc1 that impairs fungal virulence and prevents the evolution of drug resistance.

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.

CL-A3-7 is a viral-cell fusion inhibitor targeting the RSVF protein. It functions by blocking the interaction between the virus and the host's IGF1R, effectively inhibiting the infection of both wild-type and K394R mutant strains of RSV. This compound is suitable for use in antiviral drug development and resistance studies related to RSV.

AR antagonist 9 is an orally active, selective androgen receptor (AR) antagonist that inhibits cancer by disrupting the formation of AR ligand-binding domain dimers, showing potential in overcoming drug resistance in prostate cancer (PCa). Its antagonistic activity against AR has an IC50 of 0.051 μM, comparable to Enzalutamide (IC50= 0.060 μM). This compound demonstrates superior inhibitory effects on ARF876L T877A and ARW741C mutants compared to Enzalutamide. Additionally, AR antagonist 9 possesses favorable pharmacokinetic properties, with an oral bioavailability (F) of 66.24% in rats, and significantly inhibits tumor growth in LNCaP xenograft mouse models upon oral administration. AR antagonist 9 holds promise for research in overcoming PCa resistance.

AK-968-11563024 is an inhibitor targeting marine V. vulnificus NAT [(VIBVN)NAT] with an IC50 value of 18.86 µM. In V. vulnificus, NAT (aromatic amine N-acetyltransferase) plays a role in drug metabolism, contributing to drug resistance. Thus, AK-968-11563024 can be used for research related to drug tolerance.

Compound H26, a derivative of corosolic acid, functions as Hypoglycemic agent 3. It exhibits lipid-lowering and significant blood glucose-reducing properties, making it a potential hypoglycemic drug. Hypoglycemic agent 3 targets MCCC1 to mitigate insulin resistance, and may be useful in researching type 2 diabetes.

Lysosomal P-gp targeted agent 1 (Compound 14) is an antitumor drug that targets lysosomal P-glycoprotein (Pgp). It is selectively transported to lysosomes via overexpressed Pgp, releasing nitric oxide that generates reactive oxygen species (ROS), causing lysosomal membrane permeabilization (LMP) and inducing apoptosis. This compound can overcome resistance mediated by P-glycoprotein, leading to cell cycle arrest while maintaining relatively low toxicity to normal cells. It exhibits antitumor activity by significantly inhibiting tumor growth.

AKR1Cs-IN-1 (Compound 29) is an effective and broad-spectrum inhibitor of the Aldo-Keto Reductase 1C family (AKR1C1-1C4). It achieves subtype inhibition by simultaneously binding to the SP2 and SP3 pockets, thereby blocking metabolic pathways related to drug resistance. In enzyme assays, AKR1Cs-IN-1 exhibits significant inhibitory activity with IC50 values of 0.09, 0.28, 0.05, and 0.51 µM for AKR1C1, AKR1C2, AKR1C3, and AKR1C4, respectively. The compound shows excellent resensitizing effects in doxorubicin (DOX)-resistant breast cancer cell line MCF-7/ADR, effectively enhancing the cytotoxicity of DOX. AKR1Cs-IN-1 holds promise for research on breast cancer resistance.

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.

GPV0057 (Compound 5d) is a potent and selective inhibitor of P-glycoprotein (P-gp). It also acts as a selective activator of the potassium channel Kir2.1. By competitively binding at the substrate binding site of P-gp, GPV0057 inhibits ATP-dependent drug efflux, thereby reversing multidrug resistance in tumor cells. Additionally, it stabilizes the open state of Kir2.1, enhancing potassium ion influx. GPV0057 has potential applications in the study of tumors with high P-gp expression and Kir2.1-related diseases, such as heart failure and Andersen-Tawil syndrome.