Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOI92F)

• DTT Name: Multidrug resistance-associated protein 1 (ABCC1)
• Synonyms: MRP1; MRP; Leukotriene C(4) transporter; LTC4 transporter; ATP-binding cassette sub-family C member 1
• Gene Name: ABCC1
• DTT Type: Successful target; [1]
• BioChemical Class: ABC transporter
• UniProt ID: MRP1_HUMAN
• TTD ID: T11288
• EC Number: EC 7.6.2.2
• Sequence:
  MALRGFCSADGSDPLWDWNVTWNTSNPDFTKCFQNTVLVWVPCFYLWACFPFYFLYLSRH
  DRGYIQMTPLNKTKTALGFLLWIVCWADLFYSFWERSRGIFLAPVFLVSPTLLGITMLLA
  TFLIQLERRKGVQSSGIMLTFWLVALVCALAILRSKIMTALKEDAQVDLFRDITFYVYFS
  LLLIQLVLSCFSDRSPLFSETIHDPNPCPESSASFLSRITFWWITGLIVRGYRQPLEGSD
  LWSLNKEDTSEQVVPVLVKNWKKECAKTRKQPVKVVYSSKDPAQPKESSKVDANEEVEAL
  IVKSPQKEWNPSLFKVLYKTFGPYFLMSFFFKAIHDLMMFSGPQILKLLIKFVNDTKAPD
  WQGYFYTVLLFVTACLQTLVLHQYFHICFVSGMRIKTAVIGAVYRKALVITNSARKSSTV
  GEIVNLMSVDAQRFMDLATYINMIWSAPLQVILALYLLWLNLGPSVLAGVAVMVLMVPVN
  AVMAMKTKTYQVAHMKSKDNRIKLMNEILNGIKVLKLYAWELAFKDKVLAIRQEELKVLK
  KSAYLSAVGTFTWVCTPFLVALCTFAVYVTIDENNILDAQTAFVSLALFNILRFPLNILP
  MVISSIVQASVSLKRLRIFLSHEELEPDSIERRPVKDGGGTNSITVRNATFTWARSDPPT
  LNGITFSIPEGALVAVVGQVGCGKSSLLSALLAEMDKVEGHVAIKGSVAYVPQQAWIQND
  SLRENILFGCQLEEPYYRSVIQACALLPDLEILPSGDRTEIGEKGVNLSGGQKQRVSLAR
  AVYSNADIYLFDDPLSAVDAHVGKHIFENVIGPKGMLKNKTRILVTHSMSYLPQVDVIIV
  MSGGKISEMGSYQELLARDGAFAEFLRTYASTEQEQDAEENGVTGVSGPGKEAKQMENGM
  LVTDSAGKQLQRQLSSSSSYSGDISRHHNSTAELQKAEAKKEETWKLMEADKAQTGQVKL
  SVYWDYMKAIGLFISFLSIFLFMCNHVSALASNYWLSLWTDDPIVNGTQEHTKVRLSVYG
  ALGISQGIAVFGYSMAVSIGGILASRCLHVDLLHSILRSPMSFFERTPSGNLVNRFSKEL
  DTVDSMIPEVIKMFMGSLFNVIGACIVILLATPIAAIIIPPLGLIYFFVQRFYVASSRQL
  KRLESVSRSPVYSHFNETLLGVSVIRAFEEQERFIHQSDLKVDENQKAYYPSIVANRWLA
  VRLECVGNCIVLFAALFAVISRHSLSAGLVGLSVSYSLQVTTYLNWLVRMSSEMETNIVA
  VERLKEYSETEKEAPWQIQETAPPSSWPQVGRVEFRNYCLRYREDLDFVLRHINVTINGG
  EKVGIVGRTGAGKSSLTLGLFRINESAEGEIIIDGINIAKIGLHDLRFKITIIPQDPVLF
  SGSLRMNLDPFSQYSDEEVWTSLELAHLKDFVSALPDKLDHECAEGGENLSVGQRQLVCL
  ARALLRKTKILVLDEATAAVDLETDDLIQSTIRTQFEDCTVLTIAHRLNTIMDYTRVIVL
  DKGEIQEYGAPSDLLQQRGLFYSMAKDAGLV
• Function: Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency. Mediates export of organic anions and drugs from the cytoplasm.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Sphingolipid signaling pathway (hsa04071)
  Vitamin digestion and absorption (hsa04977)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  ABC-family proteins mediated transport (R-HSA-382556)
  Cobalamin (Cbl, vitamin B12) transport and metabolism (R-HSA-196741)
• BioCyc Pathway: MetaCyc:ENSG00000103222-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzbromarone	DMC3YUA	Gout	FA25	Approved	[1]
Sulfinpyrazone	DMEV954	Gout	FA25	Approved	[2]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pyrrolopyrimidine	DMZLFVG	Discovery agent	N.A.	Investigative	[3]
XR-9456	DMTUFI1	Discovery agent	N.A.	Investigative	[4]
XR-9504	DMIQP69	Discovery agent	N.A.	Investigative	[4]
XR-9544	DM1OZPN	Discovery agent	N.A.	Investigative	[4]
XR-9577	DMIZV6T	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	1.01E-02	0.89	1.34

References

• [1] Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transpo... Drug Metab Dispos. 2009 Jan;37(1):129-36.
• [2] Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos. 2008 Apr;36(4):631-40.
• [3] Topological model for the prediction of MRP1 inhibitory activity of pyrrolopyrimidines and templates derived from pyrrolopyrimidine. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4967-72.
• [4] Functional assay and structure-activity relationships of new third-generation P-glycoprotein inhibitors. Bioorg Med Chem. 2008 Mar 1;16(5):2448-62.