Target Information
Target General Information | Top | |||||
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Target ID |
T63194
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Target Name |
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1)
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Synonyms |
E-NPP 1; Membrane component chromosome 6 surface marker 1; Phosphodiesterase I/nucleotide pyrophosphatase 1; Plasma-cell membrane glycoprotein PC-1
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Gene Name |
ENPP1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Pseudoxanthoma elasticum ICD-11: EC40 | |||||
2 | Vitamin/non-protein cofactor absorption/transport disorder ICD-11: 5C63 | |||||
Function |
Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812, PubMed:28011303, PubMed:35147247). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812). {ECO:0000250|UniProtKB:P06802, ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:27467858, ECO:0000269|PubMed:28011303, ECO:0000269|PubMed:28964717, ECO:0000269|PubMed:35147247, ECO:0000269|PubMed:8001561, ECO:0000305|PubMed:11004006}.
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UniProt ID | ||||||
EC Number |
EC 3.1.4.1; EC 3.6.1.9
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Sequence |
MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPL
EKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNC RCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINY SSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKK CGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEW YKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLP KDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLIL ISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSC REPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNV FSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVY TPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYG RPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPL SPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTL LRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKD TSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSF YQQRKEPVSDILKLKTHLPTFSQED Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | INZ-701 | Drug Info | Phase 1/2 | Hypophosphatemic rickets | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | INZ-701 | Drug Info | [1] |
References | Top | |||||
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REF 1 | Clinical pipeline report, company report or official report of Inozyme pharma | |||||
REF 2 | ClinicalTrials.gov (NCT04686175) A Phase 1/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 Followed by an Open-Label Long-Term Extension Period in Adults With ENPP1 Deficiency. U.S.National Institutes of Health. |
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