Details of the Drug Therapeutic Target (DTT)

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

DTT Name Multidrug resistance protein 4 (ABCC4)
Synonyms Multispecific organic anion transporter B; Multidrug resistanceassociated protein 4; MRP/cMOATrelated ABC transporter; MOATB; ATPbinding cassette subfamily C member 4; ABCC4
Gene Name ABCC4
DTT Type
Literature-reported target
 [1]
BioChemical Class
ABC transporter
UniProt ID
MRP4_HUMAN
TTD ID
T39919
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLPVYQEVKPNPLQDANLCSRVFFWWLNPLFKIGHKRRLEEDDMYSVLPEDRSQHLGEEL
QGFWDKEVLRAENDAQKPSLTRAIIKCYWKSYLVLGIFTLIEESAKVIQPIFLGKIINYF
ENYDPMDSVALNTAYAYATVLTFCTLILAILHHLYFYHVQCAGMRLRVAMCHMIYRKALR
LSNMAMGKTTTGQIVNLLSNDVNKFDQVTVFLHFLWAGPLQAIAVTALLWMEIGISCLAG
MAVLIILLPLQSCFGKLFSSLRSKTATFTDARIRTMNEVITGIRIIKMYAWEKSFSNLIT
NLRKKEISKILRSSCLRGMNLASFFSASKIIVFVTFTTYVLLGSVITASRVFVAVTLYGA
VRLTVTLFFPSAIERVSEAIVSIRRIQTFLLLDEISQRNRQLPSDGKKMVHVQDFTAFWD
KASETPTLQGLSFTVRPGELLAVVGPVGAGKSSLLSAVLGELAPSHGLVSVHGRIAYVSQ
QPWVFSGTLRSNILFGKKYEKERYEKVIKACALKKDLQLLEDGDLTVIGDRGTTLSGGQK
ARVNLARAVYQDADIYLLDDPLSAVDAEVSRHLFELCICQILHEKITILVTHQLQYLKAA
SQILILKDGKMVQKGTYTEFLKSGIDFGSLLKKDNEESEQPPVPGTPTLRNRTFSESSVW
SQQSSRPSLKDGALESQDTENVPVTLSEENRSEGKVGFQAYKNYFRAGAHWIVFIFLILL
NTAAQVAYVLQDWWLSYWANKQSMLNVTVNGGGNVTEKLDLNWYLGIYSGLTVATVLFGI
ARSLLVFYVLVNSSQTLHNKMFESILKAPVLFFDRNPIGRILNRFSKDIGHLDDLLPLTF
LDFIQTLLQVVGVVSVAVAVIPWIAIPLVPLGIIFIFLRRYFLETSRDVKRLESTTRSPV
FSHLSSSLQGLWTIRAYKAEERCQELFDAHQDLHSEAWFLFLTTSRWFAVRLDAICAMFV
IIVAFGSLILAKTLDAGQVGLALSYALTLMGMFQWCVRQSAEVENMMISVERVIEYTDLE
KEAPWEYQKRPPPAWPHEGVIIFDNVNFMYSPGGPLVLKHLTALIKSQEKVGIVGRTGAG
KSSLISALFRLSEPEGKIWIDKILTTEIGLHDLRKKMSIIPQEPVLFTGTMRKNLDPFNE
HTDEELWNALQEVQLKETIEDLPGKMDTELAESGSNFSVGQRQLVCLARAILRKNQILII
DEATANVDPRTDELIQKKIREKFAHCTVLTIAHRLNTIIDSDKIMVLDSGRLKEYDEPYV
LLQNKESLFYKMVQQLGKAEAAALTETAKQVYFKRNYPHIGHTDHMVTNTSNGQPSTLTI
FETAL
Function May be an organic anion pump relevant to cellular detoxification.
KEGG Pathway
Antifolate resistance (hsa01523 )
ABC transporters (hsa02010 )
cAMP signaling pathway (hsa04024 )
Bile secretion (hsa04976 )
Reactome Pathway
ABC-family proteins mediated transport (R-HSA-382556 )
Azathioprine ADME (R-HSA-9748787 )
Paracetamol ADME (R-HSA-9753281 )
Platelet degranulation (R-HSA-114608 )

The Drug Transporter (DTP) Role of This DTT

DTT DTP Name Multidrug resistance-associated protein 4 (ABCC4) DTP Info
Gene Name ABCC4
29 Approved Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Abacavir DMMN36E Human immunodeficiency virus infection 1C62 Approved [2]
Adefovir DMM278X N. A. N. A. Approved [3]
Alprostadil DMWH7NQ Aorta coarctation Approved [4]
Cefadroxil DMMC345 Bacterial infection 1A00-1C4Z Approved [5]
Cefazolin DMPDYFR Bacteremia 1A73 Approved [5]
Ceftizoxime DM3VOGS Acute gonococcal cervicitis Approved [5]
Cholic Acid DM7OKQV Cholelithiasis DC11 Approved [2]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [6]
Cladribine DM3JDRP Hairy cell leukaemia 2A82.2 Approved [2]
Cyclophosphamide DM4O2Z7 Advanced cancer 2A00-2F9Z Approved [7]
Dehydroepiandrosterone sulfate DM4Q80H N. A. N. A. Approved [8]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [4]
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [9]
Folic Acid DMEMBJC Colorectal carcinoma Approved [10]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [2]
Glutathione DMAHMT9 Human immunodeficiency virus infection 1C62 Approved [11]
Irinotecan DMP6SC2 Adenocarcinoma 2D40 Approved [12]
Leucovorin DMUAZWG Colon adenocarcinoma Approved [10]
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [13]
Methotrexate DM2TEOL Anterior urethra cancer Approved [14]
Olmesartan medoxomil DMWBHRY High blood pressure BA00 Approved [15]
Oseltamivir DMGO72P Influenza 1E30-1E32 Approved [16]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [8]
Quercetin DM3NC4M Obesity 5B81 Approved [2]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [17]
Tenofovir DM1IS6U Chronic hepatitis B virus infection Approved [3]
Thioguanine DM7NKEV Acute lymphocytic leukaemia 2B33.3 Approved [18]
Topotecan DMP6G8T Central nervous system neoplasm Approved [19]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [2]
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⏷ Show the Full List of 29 Approved Drug(s)
6 Clinical Trial Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Camptothecin DM6CHNJ Solid tumour/cancer 2A00-2F9Z Phase 3 [2]
Resveratrol DM3RWXL Giant cell arteritis 4A44.2 Phase 3 [2]
Rubitecan DMDWU1S Human immunodeficiency virus infection 1C62 Phase 3 [2]
LE-SN38 DMW50NF Colorectal cancer 2B91.Z Phase 2 [2]
Taurocholic Acid DM2LZ8F Type-2 diabetes 5A11 Phase 1/2 [2]
PGF2alpha DM4XAU7 Solid tumour/cancer 2A00-2F9Z Clinical trial [2]
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⏷ Show the Full List of 6 Clinical Trial Drug(s)
1 Preclinical Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Azidothymidine monophosphate DM3FLMR N. A. N. A. Preclinical [20]
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7 Investigative Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
10-hydroxycamptothecin DM9WLN4 Discovery agent N.A. Investigative [2]
4-(2-Aminoethyl) benzenesulfonyl fluoride DMWHDRI N. A. N. A. Investigative [17]
AMINOHIPPURIC ACID DMUN54G Discovery agent N.A. Investigative [21]
glycocholic acid DM0SXNM Discovery agent N.A. Investigative [2]
glycodeoxycholic acid DM1XEJV Discovery agent N.A. Investigative [2]
[3H]cAMP DMZRQU7 Discovery agent N.A. Investigative [22]
[3H]estradiol-17beta-glucuronide DM3KJ45 Discovery agent N.A. Investigative [23]
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⏷ Show the Full List of 7 Investigative Drug(s)

References

1 High-throughput screening identifies Ceefourin 1 and Ceefourin 2 as highly selective inhibitors of multidrug resistance protein 4 (MRP4). Biochem Pharmacol. 2014 Sep 1;91(1):97-108.
2 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
3 Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol. 2007 Feb;71(2):619-27.
4 The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
5 Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
6 Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells. Antimicrob Agents Chemother. 2009 Jun;53(6):2410-6.
7 Interaction of oxazaphosphorines with multidrug resistance-associated protein 4 (MRP4). AAPS J. 2010 Sep;12(3):300-8.
8 Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7.
9 ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
10 Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.
11 Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
12 P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010 Dec;4(4):195-201.
13 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
14 Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther. 2007 Jan;320(1):229-35.
15 Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
16 Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21.
17 Fluo-cAMP is transported by multidrug resistance-associated protein isoform 4 in rat choroid plexus. J Neurochem. 2010 Oct;115(1):200-8.
18 Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57.
19 Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
20 MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med. 1999 Sep;5(9):1048-51.
21 Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol. 2004 Nov;15(11):2828-35.
22 cAMP regulates expression of the cyclic nucleotide transporter MRP4 (ABCC4) through the EPAC pathway. Pharmacogenet Genomics. 2014 Oct;24(10):522-6.
23 Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch. 2007 Feb;453(5):661-73.