Target Information
| Target General Information | Top | |||||
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| Target ID |
T92777
(Former ID: TTDS00291)
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| Target Name |
Intestinal maltase-glucoamylase (MGAM)
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| Synonyms |
MGAM
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| Gene Name |
MGAM
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Acute diabete complication [ICD-11: 5A2Y] | |||||
| 2 | Inborn carbohydrate metabolism error [ICD-11: 5C51] | |||||
| Function |
May serve as an alternate pathway for starch digestion when luminal alpha-amylase activity is reduced because of immaturity or malnutrition. May play a unique role in the digestion of malted dietary oligosaccharides used in food manufacturing.
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| BioChemical Class |
Glycosylase
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| UniProt ID | ||||||
| Sequence |
MARKKLKKFTTLEIVLSVLLLVLFIISIVLIVLLAKESLKSTAPDPGTTGTPDPGTTGTP
DPGTTGTTHARTTGPPDPGTTGTTPVSAECPVVNELERINCIPDQPPTKATCDQRGCCWN PQGAVSVPWCYYSKNHSYHVEGNLVNTNAGFTARLKNLPSSPVFGSNVDNVLLTAEYQTS NRFHFKLTDQTNNRFEVPHEHVQSFSGNAAASLTYQVEISRQPFSIKVTRRSNNRVLFDS SIGPLLFADQFLQLSTRLPSTNVYGLGEHVHQQYRHDMNWKTWPIFNRDTTPNGNGTNLY GAQTFFLCLEDASGLSFGVFLMNSNAMEVVLQPAPAITYRTIGGILDFYVFLGNTPEQVV QEYLELIGRPALPSYWALGFHLSRYEYGTLDNMREVVERNRAAQLPYDVQHADIDYMDER RDFTYDSVDFKGFPEFVNELHNNGQKLVIIVDPAISNNSSSSKPYGPYDRGSDMKIWVNS SDGVTPLIGEVWPGQTVFPDYTNPNCAVWWTKEFELFHNQVEFDGIWIDMNEVSNFVDGS VSGCSTNNLNNPPFTPRILDGYLFCKTLCMDAVQHWGKQYDIHNLYGYSMAVATAEAAKT VFPNKRSFILTRSTFAGSGKFAAHWLGDNTATWDDLRWSIPGVLEFNLFGIPMVGPDICG FALDTPEELCRRWMQLGAFYPFSRNHNGQGYKDQDPASFGADSLLLNSSRHYLNIRYTLL PYLYTLFFRAHSRGDTVARPLLHEFYEDNSTWDVHQQFLWGPGLLITPVLDEGAEKVMAY VPDAVWYDYETGSQVRWRKQKVEMELPGDKIGLHLRGGYIFPTQQPNTTTLASRKNPLGL IIALDENKEAKGELFWDNGETKDTVANKVYLLCEFSVTQNRLEVNISQSTYKDPNNLAFN EIKILGTEEPSNVTVKHNGVPSQTSPTVTYDSNLKVAIITDIDLLLGEAYTVEWSIKIRD EEKIDCYPDENGASAENCTARGCIWEASNSSGVPFCYFVNDLYSVSDVQYNSHGATADIS LKSSVYANAFPSTPVNPLRLDVTYHKNEMLQFKIYDPNKNRYEVPVPLNIPSMPSSTPEG QLYDVLIKKNPFGIEIRRKSTGTIIWDSQLLGFTFSDMFIRISTRLPSKYLYGFGETEHR SYRRDLEWHTWGMFSRDQPPGYKKNSYGVHPYYMGLEEDGSAHGVLLLNSNAMDVTFQPL PALTYRTTGGVLDFYVFLGPTPELVTQQYTELIGRPVMVPYWSLGFQLCRYGYQNDSEIA SLYDEMVAAQIPYDVQYSDIDYMERQLDFTLSPKFAGFPALINRMKADGMRVILILDPAI SGNETQPYPAFTRGVEDDVFIKYPNDGDIVWGKVWPDFPDVVVNGSLDWDSQVELYRAYV AFPDFFRNSTAKWWKREIEELYNNPQNPERSLKFDGMWIDMNEPSSFVNGAVSPGCRDAS LNHPPYMPHLESRDRGLSSKTLCMESQQILPDGSLVQHYNVHNLYGWSQTRPTYEAVQEV TGQRGVVITRSTFPSSGRWAGHWLGDNTAAWDQLKKSIIGMMEFSLFGISYTGADICGFF QDAEYEMCVRWMQLGAFYPFSRNHNTIGTRRQDPVSWDVAFVNISRTVLQTRYTLLPYLY TLMHKAHTEGVTVVRPLLHEFVSDQVTWDIDSQFLLGPAFLVSPVLERNARNVTAYFPRA RWYDYYTGVDINARGEWKTLPAPLDHINLHVRGGYILPWQEPALNTHLSRQKFMGFKIAL DDEGTAGGWLFWDDGQSIDTYGKGLYYLASFSASQNTMQSHIIFNNYITGTNPLKLGYIE IWGVGSVPVTSVSISVSGMVITPSFNNDPTTQVLSIDVTDRNISLHNFTSLTWISTL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T09GFP | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
| 1 | Acarbose | Drug Info | Approved | Diabetic complication | [2], [3] | |
| 2 | Miglitol | Drug Info | Approved | Diabetic complication | [3], [4] | |
| 3 | Rh-alphaglucosidase | Drug Info | Approved | Pompe disease | [5] | |
| 4 | Voglibose | Drug Info | Approved | Diabetic complication | [3] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | Alpha-glucosidase | Drug Info | Phase 3 | Muscle disease | [6] | |
| 2 | Deoxynojirimycin | Drug Info | Phase 3 | Pompe disease | [7] | |
| 3 | PAZ-320 | Drug Info | Phase 2 | Type-2 diabetes | [8] | |
| 4 | SC-49483 | Drug Info | Phase 2 | Acquired immune deficiency syndrome | [9] | |
| 5 | Celgosivir | Drug Info | Phase 1/2 | Dengue fever | [10] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | A-76202M | Drug Info | Terminated | Acquired immune deficiency syndrome | [11] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 8 Modulator drugs | + | ||||
| 1 | Acarbose | Drug Info | [12] | |||
| 2 | Rh-alphaglucosidase | Drug Info | [14] | |||
| 3 | Alpha-glucosidase | Drug Info | [15] | |||
| 4 | PAZ-320 | Drug Info | [17] | |||
| 5 | Celgosivir | Drug Info | [19] | |||
| 6 | A-76202M | Drug Info | [11] | |||
| 7 | BMN-103 | Drug Info | [15] | |||
| 8 | Imino sugars | Drug Info | [15] | |||
| Inhibitor | [+] 18 Inhibitor drugs | + | ||||
| 1 | Miglitol | Drug Info | [13] | |||
| 2 | Voglibose | Drug Info | [1] | |||
| 3 | Deoxynojirimycin | Drug Info | [16] | |||
| 4 | SC-49483 | Drug Info | [18] | |||
| 5 | Maltose | Drug Info | [20] | |||
| 6 | SALACINOL | Drug Info | [21] | |||
| 7 | 1,4-dideoxy-1,4-imino-D-arabinito | Drug Info | [22] | |||
| 8 | 2,5-Dideoxy-2,5-imino-D-mannitol | Drug Info | [22] | |||
| 9 | 2-Aminomethyl-pyrrolidine-3,4-diol | Drug Info | [23] | |||
| 10 | 2-Cyclopentylaminomethyl-pyrrolidine-3,4-diol | Drug Info | [23] | |||
| 11 | 3-(4-(4-hydroxyphenyl)phthalazin-1-ylamino)phenol | Drug Info | [24] | |||
| 12 | 4'-(p-toluenesulfonamide)-3,4-dihydroxy chalcone | Drug Info | [25] | |||
| 13 | De-O-sulfonated kotalanol | Drug Info | [21] | |||
| 14 | Double Oxidized Cysteine | Drug Info | [26] | |||
| 15 | GSC-1 | Drug Info | [15] | |||
| 16 | KOTALANOL | Drug Info | [21] | |||
| 17 | Nicotinamide-Adenine-Dinucleotide | Drug Info | [26] | |||
| 18 | PONKORANOL | Drug Info | [27] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Galactose metabolism | |||||
| 2 | Starch and sucrose metabolism | |||||
| 3 | Metabolic pathways | |||||
| 4 | Carbohydrate digestion and absorption | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Starch and Sucrose Metabolism | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Metabolism of carbohydrates | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Effects of changeover from voglibose to acarbose on postprandial triglycerides in type 2 diabetes mellitus patients. Adv Ther. 2009 Jun;26(6):660-6. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6791). | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4842). | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 6 | ClinicalTrials.gov (NCT01468181) A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus. U.S. National Institutes of Health. | |||||
| REF 7 | The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Hum Mutat. 2009 Dec;30(12):1683-92. | |||||
| REF 8 | ClinicalTrials.gov (NCT02060916) Study to Evaluate the Safety and Efficacy of PAZ320 in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT00000791) A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV. U.S. National Institutes of Health. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003977) | |||||
| REF 11 | Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D-hexopyranosides. Carbohydr Res. 2001 Oct 15;335(4):283-9. | |||||
| REF 12 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 13 | Drug therapy of postprandial hyperglycaemia. Drugs. 1999 Jan;57(1):19-29. | |||||
| REF 14 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
| REF 15 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2627). | |||||
| REF 16 | Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases. J Med Chem. 1994 Oct 28;37(22):3701-6. | |||||
| REF 17 | Treatment With Novel Galactomannan Derivative Reduces 2-Hour Postprandial Glucose Excursions in Individuals With Type 2 Diabetes Treated With Oral Medications and/or Insulin. J Diabetes Sci Technol. 2014 September; 8(5): 1018-1022. | |||||
| REF 18 | Pathology of perbutylated-N-butyl-1-deoxynojiromycin (an alpha-glucosidase-1 inhibitor) in Sprague-Dawley rats. Toxicol Pathol. 1996 Sep-Oct;24(5):531-8. | |||||
| REF 19 | Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection.Curr Opin Investig Drugs.2009 Aug;10(8):860-70. | |||||
| REF 20 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 21 | Probing the active-site requirements of human intestinal N-terminal maltase-glucoamylase: Synthesis and enzyme inhibitory activities of a six-membe... Bioorg Med Chem. 2010 Nov 15;18(22):7794-8. | |||||
| REF 22 | New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii. J Nat Prod. 2002 Feb;65(2):198-202. | |||||
| REF 23 | Derivatives of (2R,3R,4S)-2-aminomethylpyrrolidine-3,4-diol are selective alpha-mannosidase inhibitors. Bioorg Med Chem Lett. 2001 Sep 17;11(18):2489-93. | |||||
| REF 24 | Discovery of novel alpha-glucosidase inhibitors based on the virtual screening with the homology-modeled protein structure. Bioorg Med Chem. 2008 Jan 1;16(1):284-92. | |||||
| REF 25 | Sulfonamide chalcone as a new class of alpha-glucosidase inhibitors. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5514-6. | |||||
| REF 26 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 27 | Probing the active-site requirements of human intestinal N-terminal maltase glucoamylase: the effect of replacing the sulfate moiety by a methyl et... Bioorg Med Chem Lett. 2010 Oct 1;20(19):5686-9. | |||||
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