Molecule Information

General Information of the Molecule (ID: Mol04205)

• Name: P-glycoprotein (ABCB1) ,Homo sapiens
• Synonyms: P-glycoprotein (ABCB1)
• Molecule Type: Protein

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: cancer [ICD-11: 2D4Z] [1]

• Resistant Disease: cancer [ICD-11: 2D4Z]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; T790M; C797S
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HBL-100/DOX cells; epithelial cell; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microculture tetrazolium assay
• Mechanism Description: The investigated bis-benzimidazole-pyrroles did not belong to the P-gp substrates. The HBL-100/DOX resistance to DB2Py(4) was 9-fold higher if compared to that to HBL-100, whereas the resistance of P-gpoverexpressing cells to such classical P-gp substrates as doxorubicin and paclitaxel increased 50-100 times and more. In this respect, a conclusion can be drawn that DB2Py(4) is a weak P-gp substrate; i.e., only the monomeric MB2Py and MB2Py(Ac) are able to completely overcome the MDR associated with P-gp overexpression.

Ivermectin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [2]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Ivermectin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562/FLM cells; Blood; Homo sapiens (Human); CVCL_E7CM
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: It was found that ivermectin effectively suppressed the expression of autophagy and transport proteins in K562/FLM cells, reduced the activity of the aforementioned phosphoproteins, and promoted apoptotic cell death. The significant effects of ivermectin might offer a novel therapeutic strategy to overcome flumatinib resistance and optimize the treatment outcomes of CML.

Lapatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [3]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Lapatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Athymic nude mice model; Mus musculus
• Experiment for Molecule Alteration: CD spectroscopy assay; SDS-PAGE assay
• Experiment for Drug Resistance: Cell viability assay; Fluorescence microscope assay
• Mechanism Description: HER2-positive breast cancer constitutes 20 % of reported cases, characterized by excessive expression of HER2 receptors, pivotal in cell signaling and growth. Immunotherapy, the established treatment, often leads to multidrug resistance and tumor recurrence. There's a critical need for an effective strategy delaying drug resistance onset and ensuring cancer cell eradication. This study aimed to develop nanoparticles using human serum albumin (HSA) coupled with vitamin E (alpha-tocopherol succinate), loaded with a tyrosine kinase inhibitor (TKI) or aromatase inhibitor (AI). Nanoparticles were formed via desolvation, where HSA(VE) conjugates self-organized into a nanoparticle structure, incorporating TKI/AI either through chemical conjugation or direct binding to HSA. Physico-chemical analyses-such as infrared spectroscopy (IR), gel permeation chromatography (GPC), UV, IR, and CD spectroscopy confirmed HSA(VE) binding and drug incorporation into nanoparticles, evaluating their drug entrapment, release efficiency. Cell viability assays and in-vitro experiments on resistant and sensitive cell lines demonstrated effective drug encapsulation and absorption over time. Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

Clinical Trial Drug(s) 1 drug(s) in total

Flumatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [2]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Flumatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562/FLM cells; Blood; Homo sapiens (Human); CVCL_E7CM
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Through cellular experimentation, we explored the resistance mechanisms, which indicated that K562/FLM cells evade flumatinib cytotoxicity by enhancing autophagy, increasing the expression of membrane transport proteins, particularly P-glycoprotein, ABCC1 and ABCC4, as well as enhancing phosphorylation of p-EGFR, p-ERK and p-STAT3 proteins.

Investigative Drug(s) 2 drug(s) in total

DB2Py

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: cancer [ICD-11: 2D4Z] [1]

• Sensitive Disease: cancer [ICD-11: 2D4Z]
• Sensitive Drug: DB2Py
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HBL-100/DOX cells; epithelial cell; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microculture tetrazolium assay
• Mechanism Description: The investigated bis-benzimidazole-pyrroles did not belong to the P-gp substrates. The HBL-100/DOX resistance to DB2Py(4) was 9-fold higher if compared to that to HBL-100, whereas the resistance of P-gpoverexpressing cells to such classical P-gp substrates as doxorubicin and paclitaxel increased 50-100 times and more. In this respect, a conclusion can be drawn that DB2Py(4) is a weak P-gp substrate; i.e., only the monomeric MB2Py and MB2Py(Ac) are able to completely overcome the MDR associated with P-gp overexpression.

MB2Py

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: cancer [ICD-11: 2D4Z] [1]

• Sensitive Disease: cancer [ICD-11: 2D4Z]
• Sensitive Drug: MB2Py
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HBL-100/DOX cells; epithelial cell; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microculture tetrazolium assay
• Mechanism Description: The investigated bis-benzimidazole-pyrroles did not belong to the P-gp substrates. The HBL-100/DOX resistance to DB2Py(4) was 9-fold higher if compared to that to HBL-100, whereas the resistance of P-gpoverexpressing cells to such classical P-gp substrates as doxorubicin and paclitaxel increased 50-100 times and more. In this respect, a conclusion can be drawn that DB2Py(4) is a weak P-gp substrate; i.e., only the monomeric MB2Py and MB2Py(Ac) are able to completely overcome the MDR associated with P-gp overexpression.

References

• Ref 1: Dimeric Bis-Benzimidazole-Pyrroles DB2Py(n) - AT-Site-Specific Ligands: Synthesis, Physicochemical Analysis, and Biological Activity. Acta Naturae. 2024 Jan-Mar;16(1):86-100.
• Ref 2: Overcoming flumatinib resistance in chronic myeloid leukaemia: Insights into cellular mechanisms and ivermectin's therapeutic potential. J Cell Mol Med. 2024 Jul;28(14):e18539.
• Ref 3: Combination therapy of Lapatinib/Letrozole-based protein-vitamin nanoparticles to enhance the therapeutic effectiveness in drug-resistant breast cancer. Colloids Surf B Biointerfaces. 2025 Mar;247:114399.