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Target not currently curated in GtoImmuPdb
Target id: 768
Nomenclature: ABCB1
Abbreviated Name: MDR1, PGP1
Systematic Nomenclature: ABCB1
Family: ABCB subfamily
Gene and Protein Information  |
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| 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 |
| 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 |
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| 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 |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific inhibitor tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laniquidar (R101933) is a third generation P-gp inhibitor that reached phase 2 clinical evaluation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Biologically Significant Variant Comments |
| Nonsense mutation in ABCB1 has been described in collie dogs [5,7] 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]. |
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. Horie K, Tang F, Borchardt RT. (2003) Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res, 20 (2): 161-8. [PMID:12636153]
4. 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]
5. Mealey KL. (2004) Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther, 27 (5): 257-64. [PMID:15500562]
6. 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]
7. 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]
8. 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]
9. 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]
10. 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]
11. 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]
12. Wang S, Wang SQ, Chen XB, Xu Q, Deng H, Teng QX, Chen ZS, Zhang X, Chen FE. (2024) Cell-Based Screen Identifies a Highly Potent and Orally Available ABCB1 Modulator for Treatment of Multidrug Resistance. J Med Chem, 67 (21): 18764-18780. [PMID:39425773]
13. 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]
14. 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]
