Top ▲

ABCB1

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 768

Nomenclature: ABCB1

Abbreviated Name: MDR1, PGP1

Systematic Nomenclature: ABCB1

Family: ABCB subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 1280 7q21.12 ABCB1 ATP binding cassette subfamily B member 1
Mouse 12 1276 5 3.43 cM Abcb1a ATP-binding cassette, sub-family B member 1A
Rat - - Abcb1a ATP binding cassette subfamily B member 1A
Previous and Unofficial Names Click here for help
ABC20 | Abcb1 | Abcb1a | ATP-binding cassette | ATP-binding cassette, sub-family B (MDR/TAP), member 1 | ATP-binding cassette, subfamily B (MDR/TAP), member 1A | ATP binding cassette subfamily B member 1 | CD243 | CLCS | colchicin sensitivity | Evi32 | GP170 | MDR1 | Mdr1a | MDR3 | mdr-3 | multidrug resistance protein 1 | multiple drug resistant 1a | P-glycoprotein 1 | Pgp | P-gp | PGY1 | Pgy3 | Pgy-3
Database Links Click here for help
Alphafold P08183 (Hs), P21447 (Mm)
ChEMBL Target CHEMBL4302 (Hs), CHEMBL2573 (Mm)
DrugBank Target P08183 (Hs)
Ensembl Gene ENSG00000085563 (Hs), ENSMUSG00000040584 (Mm), ENSRNOG00000008012 (Rn)
Entrez Gene 5243 (Hs), 18671 (Mm), 170913 (Rn)
Human Protein Atlas ENSG00000085563 (Hs)
KEGG Gene hsa:5243 (Hs), mmu:18671 (Mm), rno:170913 (Rn)
OMIM 171050 (Hs)
Pharos P08183 (Hs)
UniProtKB P08183 (Hs), P21447 (Mm)
Wikipedia ABCB1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Molecular structure of human P-glycoprotein (ABCB1) in the ATP-bound, outward-facing conformation
PDB Id:  6C0V
Ligand:  ATP   This ligand is endogenous
Resolution:  3.4Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Encequidar-bound human P-glycoprotein in complex with UIC2-Fab
PDB Id:  7O9W
Ligand:  encequidar
Resolution:  3.5Å
Species:  Human
References:  9

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
zosuquidar Small molecule or natural product Hs Inhibition 7.2 pKi 2
⤷ pKi 7.2 (Ki 5.9x10-8 M) [2]
valspodar Peptide Hs Inhibition 5.9 pKi 12
⤷ pKi 5.9 (Ki 1.3x10-6 M) [12]
WS-898 Small molecule or natural product Hs Inhibition 8.3 pIC50 11
⤷ pIC50 8.3 (IC50 5x10-9 M) [11]
tariquidar Small molecule or natural product Ligand has a PDB structure Mm Inhibition 7.4 pIC50 5
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [5]
Description: Measuring the effect of XR9576 on accumulation of [3H] daunorubicin in the multidrug resistant mouse mammary carcinoma cell line EMT6/AR1.0
encequidar Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.3 pIC50 8
⤷ pIC50 7.3 (IC50 5.3x10-8 M) [8]
Description: Inhibition of P-gp-mediated paclitaxel efflux from Caco-2 cells
compound 14 [PMID: 30925062] Small molecule or natural product Click here for species-specific activity table Hs Competitive 5.8 – 6.2 pIC50 7
⤷ pIC50 6.2 (IC50 6.76x10-7 M) [7]
Description: Measuring inhibition of cyclosporine A transport in A2780/ADR cells expressing hABCB1.
pIC50 5.8 (IC50 1.73x10-6 M) [7]
Description: Measuring inhibition of calcein AM transport in A2780/ADR cells expressing hABCB1.
biricodar Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pIC50 10
⤷ pIC50 5.3 (IC50 5x10-6 M) [10]
View species-specific inhibitor tables
Inhibitor Comments
Laniquidar (R101933) is a third generation P-gp inhibitor that reached phase 2 clinical evaluation.
Biologically Significant Variant Comments
Nonsense mutation in ABCB1 has been described in collie dogs [4,6] and when these animals are treated with ivermectin they develop potentially fatal neurologic disorders, due to a toxic accumulation of ivermectin in the central nervous system. Similar ivermectin-induced pathology has been noted in humans. In 2020 mutated human ABCB1 alleles were identified in a patient who developed serious ivermectin toxicity following a single oral dose of the drug. Genetic analysis revealed that this patient harboured a different nonsense alteration in each copy of their ABCB1 genes. Both mutations generated premature stop codons and truncated transporter proteins that lacked the C-terminal nucleotide-binding domain, rendering the proteins incapable of drug-transport [1].

References

Show »

1. Baudou E, Lespine A, Durrieu G, André F, Gandia P, Durand C, Cunat S. (2020) Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations. N Engl J Med, 383: 787-789 [Epub ahead of print]. DOI: 10.1056/NEJMc1917344

2. Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS, Binkley SN, Kuhfeld MT, Starling JJ, Wrighton SA. (1999) Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther, 290 (2): 854-62. [PMID:10411602]

3. Kim Y, Chen J. (2018) Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation. Science, 359 (6378): 915-919. [PMID:29371429]

4. Mealey KL. (2004) Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther, 27 (5): 257-64. [PMID:15500562]

5. Roe M, Folkes A, Ashworth P, Brumwell J, Chima L, Hunjan S, Pretswell I, Dangerfield W, Ryder H, Charlton P. (1999) Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett, 9 (4): 595-600. [PMID:10098671]

6. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, Mol CA, van der Valk MA, Robanus-Maandag EC, te Riele HP et al.. (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell, 77 (4): 491-502. [PMID:7910522]

7. Silbermann K, Stefan SM, Elshawadfy R, Namasivayam V, Wiese M. (2019) Identification of Thienopyrimidine Scaffold as an Inhibitor of the ABC Transport Protein ABCC1 (MRP1) and Related Transporters Using a Combined Virtual Screening Approach. J Med Chem, 62 (9): 4383-4400. [PMID:30925062]

8. Smolinski MP, Urgaonkar S, Pitzonka L, Cutler M, Lee G, Suh KH, Lau JYN. (2021) Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem, 64 (7): 3677-3693. [PMID:33729781]

9. Urgaonkar S, Nosol K, Said AM, Nasief NN, Bu Y, Locher KP, Lau JYN, Smolinski MP. (2022) Discovery and Characterization of Potent Dual P-Glycoprotein and CYP3A4 Inhibitors: Design, Synthesis, Cryo-EM Analysis, and Biological Evaluations. J Med Chem, 65 (1): 191-216. [PMID:34928144]

10. Wang S, Ryder H, Pretswell I, Depledge P, Milton J, Hancox TC, Dale I, Dangerfield W, Charlton P, Faint R et al.. (2002) Studies on quinazolinones as dual inhibitors of Pgp and MRP1 in multidrug resistance. Bioorg Med Chem Lett, 12 (4): 571-4. [PMID:11844674]

11. Wang S, Wang SQ, Teng QX, Lei ZN, Chen ZS, Chen XB, Liu HM, Yu B. (2021) Discovery of the Triazolo[1,5-a]Pyrimidine-Based Derivative WS-898 as a Highly Efficacious and Orally Bioavailable ABCB1 Inhibitor Capable of Overcoming Multidrug Resistance. J Med Chem, 64 (21): 16187-16204. [PMID:34723530]

12. Wigler PW. (1999) PSC833, cyclosporin A, and dexniguldipine effects on cellular calcein retention and inhibition of the multidrug resistance pump in human leukemic lymphoblasts. Biochem Biophys Res Commun, 257 (2): 410-3. [PMID:10198227]

Contributors

Show »

How to cite this page