Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTP (ID: DTCSGPB)

• DTP Name: Multidrug resistance-associated protein 4 (ABCC4) DTP Info
• Gene Name: MRP4

Molecule-Related Drug & Molecule List

29 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[1]
Adefovir	DMM278X	N. A.	N. A.	Approved	[2]
Alprostadil	DMWH7NQ	Aorta coarctation		Approved	[3]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[4]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[4]
Ceftizoxime	DM3VOGS	Acute gonococcal cervicitis		Approved	[4]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[1]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[5]
Cladribine	DM3JDRP	Hairy cell leukaemia	2A82.2	Approved	[1]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[6]
Dehydroepiandrosterone sulfate	DM4Q80H	N. A.	N. A.	Approved	[7]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[3]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[8]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[9]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[1]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[10]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[11]
Leucovorin	DMUAZWG	Colon adenocarcinoma		Approved	[9]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Olmesartan medoxomil	DMWBHRY	High blood pressure	BA00	Approved	[14]
Oseltamivir	DMGO72P	Influenza	1E30-1E32	Approved	[15]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[1]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[16]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[2]
Thioguanine	DM7NKEV	Acute lymphocytic leukaemia	2B33.3	Approved	[17]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[1]

6 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Camptothecin	DM6CHNJ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[1]
Rubitecan	DMDWU1S	Human immunodeficiency virus infection	1C62	Phase 3	[1]
LE-SN38	DMW50NF	Colorectal cancer	2B91.Z	Phase 2	[1]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[1]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[1]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Azidothymidine monophosphate	DM3FLMR	N. A.	N. A.	Preclinical	[19]

7 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
10-hydroxycamptothecin	DM9WLN4	Discovery agent	N.A.	Investigative	[1]
4-(2-Aminoethyl) benzenesulfonyl fluoride	DMWHDRI	N. A.	N. A.	Investigative	[16]
AMINOHIPPURIC ACID	DMUN54G	Discovery agent	N.A.	Investigative	[20]
glycocholic acid	DM0SXNM	Discovery agent	N.A.	Investigative	[1]
glycodeoxycholic acid	DM1XEJV	Discovery agent	N.A.	Investigative	[1]
[3H]cAMP	DMZRQU7	Discovery agent	N.A.	Investigative	[21]
[3H]estradiol-17beta-glucuronide	DM3KJ45	Discovery agent	N.A.	Investigative	[22]

References

• [1] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [2] 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.
• [3] 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.
• [4] Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
• [5] 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.
• [6] Interaction of oxazaphosphorines with multidrug resistance-associated protein 4 (MRP4). AAPS J. 2010 Sep;12(3):300-8.
• [7] 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.
• [8] ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Fluo-cAMP is transported by multidrug resistance-associated protein isoform 4 in rat choroid plexus. J Neurochem. 2010 Oct;115(1):200-8.
• [17] Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57.
• [18] Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
• [19] MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med. 1999 Sep;5(9):1048-51.
• [20] 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.
• [21] cAMP regulates expression of the cyclic nucleotide transporter MRP4 (ABCC4) through the EPAC pathway. Pharmacogenet Genomics. 2014 Oct;24(10):522-6.
• [22] Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch. 2007 Feb;453(5):661-73.