MDR-1

Synonyms

ATP-Dependent Translocase ABCB1, EC:7.6.2.2, EC 7.6.2.2, Phospholipid Transporter ABCB1, P-Glycoprotein 1, PGY1, Doxorubicin Resistance, P Glycoprotein, CD243 Antigen, EC 3.6.3.44, ABC20, CD243, GP170, P-GP, CLCS, ATP Binding Cassette Transporter, Subfamily B, Member 1, Multidrug resistance protein 1, EC 3.6.3, EC 7.6.2.1, EC:7.6.2.1, MDR1, ABCB1, ATP-binding cassette sub-family B member 1, ATP Binding Cassette Subfamily B Member 1, ATP-Binding Cassette, Sub-Family B (MDR/TAP), Member 1, Colchicin Sensitivity

Description

P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. Translocates drugs and phospholipids across the membrane . Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins . Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.

KO Status

F2 (-/-)

Drug Information

Launched drugs: 6
Drugs in clinical trials: 12
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Dapagliflozin Propanediol Monohydrate

HGP-1812, BMS-512148, BMS-512148-05, HGP-1602, ATB-1012

Approved

Bristol-Myers Squibb Company

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Heart Failure, Hyperuricemia, Myocardial Infarction, Kidney Diseases, Hyperglycemia, Hypertension, Cardiovascular Diseases, Renal Insufficiency, Chronic, Diabetes Mellitus

Paclitaxel/Encequidar mesylate

Approved

Hanmi Pharmaceutical Co Ltd

Solid tumours, Hemangiosarcoma, Breast Neoplasms, Adenocarcinoma

Piperine

Tezacaftor/Ivacaftor

VX-661/VX-770, VX-770/VX-661

Approved

Vertex Pharmaceuticals Incorporated

Cystic Fibrosis

Ivacaftor/Lumacaftor

Approved

Vertex Pharmaceuticals Incorporated

Cystic Fibrosis

Ivacaftor

VX-770

Approved

Vertex Pharmaceuticals Incorporated

Ciliary Motility Disorders, Cystic Fibrosis, Hepatic Insufficiency

Elexacaftor/ivacaftor/tezacaftor

VX445/VX661/VX770

Approved

Vertex Pharmaceuticals Incorporated

Cystic Fibrosis

Isoniazid/Piperine/Rifampicin

Approved

Cadila Pharmaceuticals

Tuberculosis, Pulmonary

Deudextromethorphan

d-DM, AVP-786, CTP-786, d6-DM/Q

Phase 3 Clinical

Concert Pharmaceuticals

Solid tumours, Carcinoma, Renal Cell, Schizophrenia, Mitochondrial Diseases, Alzheimer Disease, Disruptive, Impulse Control, and Conduct Disorders, Melanoma

HE-10

HE-10, HU-004

Phase 3 Clinical

Huons

Dry Eye Syndromes, Xerophthalmia

References


Title

Authors

Source

Initial characterization of the human central proteome

Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.,

BMC Syst. Biol. 5:17-17(2011)

Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function

Katayama K., Yamaguchi M., Noguchi K., Sugimoto Y.,

Cancer Lett. 345:124-131(2014)

An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene

Choi K.H., Chen C.-J., Kriegler M., Roninson I.B.,

Cell 53:519-529(1988)

Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors

Mickley L.A., Lee J.-S., Weng Z., Zhan Z., Alvarez M., Wilson W., Bates S.E., Fojo T.,

Blood 91:1749-1756(1998)

A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein

Decleves X., Chevillard S., Charpentier C., Vielh P., Laplanche J.-L.,

Hum. Mutat. 15:486-486(2000)

Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo

Hoffmeyer S., Burk O., von Richter O., Arnold H.P., Brockmoeller J., Johne A., Cascorbi I., Gerloff T., Roots I., Eichelbaum M., Brinkmann U.,

Proc. Natl. Acad. Sci. U.S.A. 97:3473-3478(2000)

Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects

Cascorbi I., Gerloff T., Johne A., Meisel C., Hoffmeyer S., Schwab M., Schaeffeler E., Eichelbaum M., Brinkmann U., Roots I.,

Clin. Pharmacol. Ther. 69:169-174(2001)

Polymorphism of MDR1 gene in healthy Japanese subjects: a novel SNP with an amino acid substitution (Glu108Lys)

Honda T., Dan Y., Koyabu N., Ieiri I., Otsubo K., Higuchi S., Ohtani H., Sawada J.,

Drug Metab. Pharmacokinet. 17:479-481(2002)

Twelve novel single nucleotide polymorphisms in ABCB1/MDR1 among Japanese patients with ventricular tachycardia who were administered amiodarone

Itoda M., Saito Y., Komamura K., Ueno K., Kamakura S., Ozawa S., Sawada J.,

Drug Metab. Pharmacokinet. 17:566-571(2002)

Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population

Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S., Nakamura Y.,

J. Hum. Genet. 47:38-50(2002)