Molecule Information

General Information of the Molecule (ID: Mol00805)

• Name: ATP-binding cassette sub-family B5 (ABCB5) ,Mus musculus
• Synonyms: ABCB5 P-gp; P-glycoprotein ABCB5
• Molecule Type: Protein
• Gene Name: Abcb5
• Gene ID: 77706
• Location: chr 12: 118831559-118930156[-]
• Sequence:
  MANSERTNGLQETNQRYGPLQEQVPKVGNQAVGPIEIFRFADNLDIVLMTLGILASMING
  ATVPLMSLVLGEISDHLINGCLVQTNRTKYQNCSQTQEKLNEDIIVLTLYYIGIGAAALI
  FGYVQISFWVITAARQTTRIRKQFFHSILAQDISWFDGSDICELNTRMTGDINKLCDGIG
  DKIPLMFQNISGFSIGLVISLIKSWKLSLVVLSTSPLIMASSALCSRMIISLTSKELDAY
  SKAGAVAEEALSSIQTVTAFGAQEKEIQRYTQHLKDAKDAGIKRATASKLSLGAVYFFMN
  GAYGLAFWYGTSLIFGGEPGYTIGTILAVFFSVIHSSYCIGSVAPHLETFTVARGAAFNI
  FQVIDKKPNIDNFSTAGFVPECIEGNIEFKNVSFSYPSRPSAKVLKGLNLKIKAGETVAL
  VGPSGSGKSTTVQLLQRLYDPEDGCITVDENDIRAQNVRHYREQIGVVRQEPVLFGTTIG
  NNIKFGREGVGEKEMEQAAREANAYDFIMAFPKKFNTLVGEKGAQMSGGQKQRIAIARAL
  VRNPKILILDEATSALDTESESLVQTALEKASKGRTTIVVAHRLSTIRGADLIVTMKDGM
  VVEKGTHAELMAKQGLYYSLAMAQDIKKVDEQMESRTCSTAGNASYGSLCDVNSAKAPCT
  DQLEEAVHHQKTSLPEVSLLKIFKLSKSEWPFVVLGTLASALNGSVHPVFSIIFGKLVTM
  FEDKNKATLKQDAELYSMMLVVLGIVALVTYLMQGLFYGRAEENLAMRLRHSAFKAMLYQ
  DMAWYDDKENNTGALTTTLAVDVAQIQGAATSRLGIVTQDVSNMSLSILISFIYGWEMTL
  LILSFAPVLAVTGMIQTAAMAGFANRDKQALKRAGKIATEAVENIRTVVSLTRERAFEQM
  YEETLQTQHRNALKRAHITGCCYAVSHAFVHFAHAAGFRFGAYLIQAGRMMPEGMFIVFT
  AIAYGAMAIGETLVWAPEYSKAKAGASHLFALLKNKPTINSCSQSGEKPDTCEGNLEFRE
  VSFVYPCRPEVPVLQNMSLSIEKGKTVAFVGSSGCGKSTCVQLLQRFYDPMKGQVLLDGV
  DVKELNVQWLRSQTAIVSQEPVLFNCSIAENIAYGDNSRMVPLEEIKEVADAANIHSFIE
  GLPRKYNTLVGLRGVQLSGGQKQRLAIARALLRKPKILLLDEATSALDNESEKVVQQALD
  KARRGKTCLVVAHRLSTIQNADMIVVLQNGSIKEQGTHQELLRNGDTYFKLVAAH
• Function: Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair.
• Uniprot ID: ABCB5_MOUSE
• Ensembl ID: ENSMUSG00000072791

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Mus
Species: Mus musculus

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) 2 drug(s) in total

Dexamethasone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Inflammation [1]

• Sensitive Disease: Inflammation [ICD-11: 1A00-CA43]
• Sensitive Drug: Dexamethasone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

Disease Class: Allergy [1]

• Sensitive Disease: Allergy [ICD-11: 4A85.0]
• Sensitive Drug: Dexamethasone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

Disease Class: Shock [1]

• Sensitive Disease: Shock [ICD-11: MG40.0]
• Sensitive Drug: Dexamethasone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

Trospium chloride

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Overactive bladder [2]

• Sensitive Disease: Overactive bladder [ICD-11: GC50.0]
• Sensitive Drug: Trospium chloride
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Mdr1a/1b double knockout mice xenograft model; Mus musculus
• Experiment for Drug Resistance: [3H]trospium chloride tissue distribution assay
• Mechanism Description: P-gp-deficient mdr1a,b(-/-) knockout mice were given either 1 mg/kg trospium chloride orally or 1 mg/kg intravenously to analyze brain penetration, intestinal secretion, and hepatobiliary excretion of the drug. The concentrations of trospium chloride in the brain were up to 7 times higher in the mdr1a,b(-/-) knockout mice compared with wild-type mice (p < 0.05), making P-gp a limiting factor for the blood-brain barrier penetration of this drug. Moreover, the residence time of the drug in the central nervous system was significantly prolonged in mdr1a,b(-/-) knockout.

References

• Ref 1: Changes in the brain accumulation of glucocorticoids in abcb1a-deficient CF-1 mice. J Neuroendocrinol. 2012 Nov;24(11):1440-6. doi: 10.1111/j.1365-2826.2012.02353.x.
• Ref 2: The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride. Drug Metab Dispos. 2009 Jul;37(7):1371-4. doi: 10.1124/dmd.109.027144. Epub 2009 Apr 23.