General Information of Drug Therapeutic Target (DTT) (ID: TTJUXV6)

DTT Name Multidrug resistance protein 3 (ABCB4)
Synonyms PGY3; P-gp; MDR3; ATP-binding cassette sub-family B member 4; ABCB4
Gene Name ABCB4
DTT Type
Clinical trial target
[1]
BioChemical Class
Acid anhydrides hydrolase
UniProt ID
MDR3_HUMAN
TTD ID
T93062
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 7.6.2.1
Sequence
MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLG
TIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYY
SGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDD
ISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSA
FSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANIS
MGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANA
RGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQ
SGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPV
LFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQR
IAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVI
AGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKS
RLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIA
NGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAG
EILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIA
NLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAI
ENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGA
YLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSY
SEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQ
LLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYG
DNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQP
QILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEH
GTHQQLLAQKGIYFSMVSVQAGTQNL
Function
Mediates ATP-dependent export of organic anions and drugs from the cytoplasm. Hydrolyzes ATP with low efficiency. Not capable of conferring drug resistance. Mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte.
KEGG Pathway
ABC transporters (hsa02010 )
Bile secretion (hsa04976 )
Reactome Pathway
ABC-family proteins mediated transport (R-HSA-382556 )
PPARA activates gene expression (R-HSA-1989781 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Encequidar DMM8Z3Q Metastatic breast cancer 2C6Y Phase 2 [2]
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4 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dofequidar fumarate DMWMHU7 Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 3 [1]
LY335979 DM2KITF Acute myeloid leukaemia 2A60 Discontinued in Phase 3 [3]
Dexniguldipine DMLZIT2 Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [4]
LANIQUIDAR DM3YABD Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [5]
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The Drug Transporter (DTP) Role of This DTT

DTT DTP Name Multidrug resistance protein 3 (ABCB4) DTP Info
Gene Name ABCB4
5 Approved Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Digoxin DMQCTIH Arrhythmia BC9Z Approved [6]
Paclitaxel DMLB81S Breast carcinoma Approved [6]
SILODOSIN DMJSBT6 Benign prostatic hyperplasia GA90 Approved [7]
Verapamil DMA7PEW Angina pectoris BA40 Approved [6]
Vinblastine DM5TVS3 Advanced cancer 2A00-2F9Z Approved [6]
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References

1 Reversal of multidrug resistance by a novel quinoline derivative, MS-209. Cancer Chemother Pharmacol. 1995;35(4):271-7.
2 Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem. 2021 Apr 8;64(7):3677-3693.
3 A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxoru... Clin Cancer Res. 2004 May 15;10(10):3265-72.
4 Mechanism of action of dexniguldipine-HCl (B8509-035), a new potent modulator of multidrug resistance. Biochem Pharmacol. 1995 Mar 1;49(5):603-9.
5 Evaluation of [11C]laniquidar as a tracer of P-glycoprotein: radiosynthesis and biodistribution in rats. Nucl Med Biol. 2009 Aug;36(6):643-9.
6 MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem. 2000 Aug 4;275(31):23530-9.
7 Pharmacokinetics and disposition of silodosin (KMD-3213)]. Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45.