Molecule Information

General Information of the Molecule (ID: Mol01014)

• Name: Multidrug resistance protein 1 (ABCB1) ,Sus scrofa
• Synonyms: ABCB1; Fragment
• Molecule Type: Protein
• Gene Name: ABCB1
• Sequence:
  GQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSNEYTI
  GQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDSKPSIDSYSKNGHKPDNI
  KGNLEFRNVHFSYPSRNEVKILKGLNLKVESGQTVALVGNSGCGKSTTVQLMQRLYDPTE
  GVVSIDGQDIRTINVRYLREIIGVVSQEPVLFATTIAENIRYGRENVTMEEIEKAVKEAN
  AYDFIMKLPNKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAV
  VQVALDKAREGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGSHDELMKEKGVYFKLVTM
  QTKGNEIELENTVGVSKGVVDALDMSPKDLESSLIRRGSTRKSIKGPQGQDRKLSTKEGL
  DENVPPVSFWRILKLNITEWPYFVVGIFCAIINGGLQPAFSIIFSRIIGVFTKVTDPETK
  RQDSNIFSLLFLILGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPK
  NTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPII
  AIAGVVEMKMLSGQALKDKKELEGAGKIATEAIENFRTVVSLTREEKFESMYDQSLQVPY
  SNSLRKAHIFGITFSITQAMMYFSYAACFRFGAYLVQHGHMDFQDVLLVFSAIVFGAMAV
  GQVSSFAPDYAKAKVSASHVIMIIEKTPQIDSYSTVGLKPNTVEGNLTFNEVMFNYPTRP
  DIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLIDGREIKELNVQW
  LRAHMGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVQAAKEANIHPFIETLPDKYNTR
  VGDKGTQLSGGQKQRIAIARALVRRPRILLLDEATSALDTESEKVVQEALDKAR
• Uniprot ID: Q5MIZ9_PIG

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Artiodactyla
Family: Suidae
Genus: Sus
Species: Sus scrofa

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) 8 drug(s) in total

Chlorpromazine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Psychosis [ICD-11: 6D8Z.0] [4]

• Sensitive Disease: Psychosis [ICD-11: 6D8Z.0]
• Sensitive Drug: Chlorpromazine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: L-MDR1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• In Vitro Model: LLC-Pk1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• Experiment for Drug Resistance: Flow cytometric assay
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), is involved in efflux transport of several antipsychotics in the blood-brain barrier (BBB). All the antipsychotics showed various degrees of inhibitory effects on P-gp activity at concentrations ranging from 1 to 100 uM. However, risperidone and olanzapine are the most likely agents that may inhibit P-gp activity.

Clozapine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Psychosis [ICD-11: 6D8Z.0] [4]

• Sensitive Disease: Psychosis [ICD-11: 6D8Z.0]
• Sensitive Drug: Clozapine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: L-MDR1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• In Vitro Model: LLC-Pk1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• Experiment for Drug Resistance: Flow cytometric assay
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), is involved in efflux transport of several antipsychotics in the blood-brain barrier (BBB). All the antipsychotics showed various degrees of inhibitory effects on P-gp activity at concentrations ranging from 1 to 100 uM. However, risperidone and olanzapine are the most likely agents that may inhibit P-gp activity.

Doxorubicin

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] [3]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p-glycoprotein; Regulation; N.A.
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562 ABCB1 overexpression cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Flow Cytometry assay; DNA dye competition assay
• Mechanism Description: The ABC transporters are responsible for the efflux of a wide range of chemotherapeutics across the plasma membrane, leading to lower intracellular drug levels and treatment resistance.

Haloperidol

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Psychosis [ICD-11: 6D8Z.0] [4]

• Sensitive Disease: Psychosis [ICD-11: 6D8Z.0]
• Sensitive Drug: Haloperidol
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: L-MDR1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• In Vitro Model: LLC-Pk1 cells(Sus scrofa (Pig)); Kidney; Homo sapiens (Human); CVCL_0391
• Experiment for Drug Resistance: Flow cytometric assay
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), is involved in efflux transport of several antipsychotics in the blood-brain barrier (BBB). All the antipsychotics showed various degrees of inhibitory effects on P-gp activity at concentrations ranging from 1 to 100 uM. However, risperidone and olanzapine are the most likely agents that may inhibit P-gp activity.

Idarubicin

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] [3]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Idarubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p-glycoprotein; Regulation; N.A.
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562 ABCB1 overexpression cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Flow Cytometry assay; DNA dye competition assay
• Mechanism Description: Induction of DNA double-strand breaks and chromatin damage through histone eviction.

Melphalan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Retinoblastoma [ICD-11: 2D02.2] [5]

• Resistant Disease: Retinoblastoma [ICD-11: 2D02.2]
• Resistant Drug: Melphalan
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Similar Genomic Alterations but Distinctive Expression of Influx/Efflux Transporters Between Chemoresistant and Parental Cells

Topotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Retinoblastoma [ICD-11: 2D02.2] [5]

• Resistant Disease: Retinoblastoma [ICD-11: 2D02.2]
• Resistant Drug: Topotecan
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Similar Genomic Alterations but Distinctive Expression of Influx/Efflux Transporters Between Chemoresistant and Parental Cells

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [2]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Ubc7
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: KBV20 cells were highly resistant to Vincristine

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [2]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Ubc6
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microscopic assay
• Mechanism Description: KBV20 cells were highly resistant to Vincristine

Clinical Trial Drug(s) 2 drug(s) in total

Capivasertib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

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

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Capivasertib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7/ADR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: AZD5363 markedly increased apoptosis only in drug-sensitive MCF-7 cells, whereas the same dose of AZD5363 afforded similar levels of apoptosis in resistant MCF-7/ADR

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

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

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Capivasertib
• Molecule Alteration: Expression; S2702T
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: AZD5363 markedly increased apoptosis only in drug-sensitive MCF-7 cells, whereas the same dose of AZD5363 afforded similar levels of apoptosis in resistant MCF-7/ADR

Perifosine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

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

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Perifosine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: Perifosine afforded highly selective sensitization effects only in drug-resistant MCF-8/ADR cancer cells

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [2]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Perifosine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [2]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Perifosine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KBV20C cells; Oral epithelium; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Microscopic assay
• Mechanism Description: Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells

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

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Perifosine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7/ADR cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: Perifosine afforded highly selective sensitization effects only in drug-resistant MCF-7/ADR cancer cells

Investigative Drug(s) 1 drug(s) in total

Anthracyclines

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] [3]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Sensitive Drug: Anthracyclines
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p-glycoprotein; Regulation; N.A.
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562 ABCB1 overexpression cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Flow Cytometry assay; DNA dye competition assay
• Mechanism Description: Exert their activity exclusively through histone eviction and are generally more cytotoxic to tumor cells than their parent compound;DNA double-strand break generation versus histone eviction;Anthracyclines featuring an N,N-dimethyl aminosugar in general are poor substrates for the ABCB1 drug transporter as compared to their non-alkylated counterparts.

References

• Ref 1: Foretinib, a c-MET receptor tyrosine kinase inhibitor, tackles multidrug resistance in cancer cells by inhibiting ABCB1 and ABCG2 transporters. Toxicol Appl Pharmacol. 2024 Mar;484:116866.
• Ref 2: Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells. Biomol Ther (Seoul). 2025 Jan 1;33(1):170-181.
• Ref 3: Novel N,N-Dimethyl-idarubicin Analogues Are Effective Cytotoxic Agents for ABCB1-Overexpressing, Doxorubicin-Resistant Cells. J Med Chem. 2024 Aug 22;67(16):13802-13812.
• Ref 4: Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• Ref 5: Mimicking Retinoblastoma Treatment With Repeated Topotecan or Melphalan Develops Cross-Resistance to Classic Agents But Not to Repurposed Drugs. Invest Ophthalmol Vis Sci. 2024 Dec 2;65(14):14.