Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMR5UV)

DTT Name	Alkaline phosphatase tissue-nonspecific (ALPL)
Synonyms	TNSALP; Liver/bone/kidney isozyme; Alkaline phosphatase, tissue-nonspecific isozyme; Alkaline phosphatase liver/bone/kidney isozyme; AP-TNAP
Gene Name	ALPL
DTT Type	Successful target	[1]
BioChemical Class	Phosphoric monoester hydrolase
UniProt ID	PPBT_HUMAN
TTD ID	T09538
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 3.1.3.1
Sequence	MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGD GMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCG VKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAH SADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDE KARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELN RNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIG QAGSLTSSEDTLTVVTADHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPG YKVVGGERENVSMVDYAHNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYV PHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF
Function	This isozyme plays a key role in skeletal mineralization by regulating levels of diphosphate (PPi).
KEGG Pathway	Folate biosynthesis (hsa00790 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Post-translational modification (R-HSA-163125 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Asfotase alfa	DMM4FXA	Genetic disease	8E02	Approved	[1]
Levamisole	DM5EN79	Parasitic infection	1D0Y-1G2Z	Approved	[2]
------------------------------------------------------------------------------------

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DS-1211	DMY3T0L	Pseudoxanthoma elasticum	EC40	Phase 2	[3]
ALXN1850	DMSQPCT	Hypophosphatasia	5C64.3	Phase 1	[4]
ALXN1910	DMDXTAE	Discovery agent	N.A.	Phase 1	[4]
------------------------------------------------------------------------------------

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Colon cancer	2C82	Colon tissue	4.67E-13	-0.15	-0.79
------------------------------------------------------------------------------------

The Drug-Metabolizing Enzyme (DME) Role of This DTT

DTT DME Name

Alkaline phosphatase (ALPL) DME Info

Gene Name

ALPL

3 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amifostine	DM5FL14	Mucositis	CA00	Approved	[5]
Fospropofol	DM8J5XT	N. A.	N. A.	Approved	[6]
Fostamatinib	DM6AUHV	Immune thrombocytopenic purpura	3B64.13	Approved	[]
------------------------------------------------------------------------------------

References

1	Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13.
2	Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity. Braz J Med Biol Res. 2008 Jul;41(7):600-9.
3	In Vitro and In Vivo Pharmacological Profiles of DS-1211, a Novel Potent, Selective, and Orally Bioavailable Tissue-Nonspecific Alkaline Phosphatase Inhibitor. J Bone Miner Res. 2022 Oct;37(10):2033-2043.
4	Clinical pipeline report, company report or official report of Alexion
5	Pharmacokinetic profile of amifostine. Semin Oncol. 1996 Aug;23(4 Suppl 8):18-22.
6	A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations. Am J Ther. 2013 Mar-Apr;20(2):163-71.