Target Information

Target General Infomation
Target ID
T92777
Former ID
TTDS00291
Target Name
Maltase-glucoamylase, intestinal
Gene Name
MGAM
Synonyms
Alpha-glucosidase; MGAM
Target Type
Successful
Disease Acquired immune deficiency syndrome [ICD9: 42; ICD10: B20]
Cardiovascular disorder [ICD10: I00-I99]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Dengue fever [ICD9: 61; ICD10: A90]
Hyperglycemia [ICD9: 790.29; ICD10: R73.9]
Muscle disease [ICD10: M60-M63]
Pompe's disease [ICD10: E74.02]
Type 2 diabetes [ICD9: 250; ICD10: E11]
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.
BioChemical Class
Glycosylases
Target Validation
T92777
UniProt ID
O43451
EC Number
EC 3.2.1.3
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
Drugs and Mode of Action
Drug(s) Acarbose Drug Info Approved Diabetes [536361], [541872]
Miglitol Drug Info Approved Diabetes [468076], [536361]
Rh-alphaglucosidase Drug Info Approved Pompe's disease [551871]
Voglibose Drug Info Approved Diabetes [536361]
Acarbose Drug Info Phase 3 Cardiovascular disorder [536361], [541872]
Alpha-glucosidase Drug Info Phase 3 Muscle disease [523686]
Deoxynojirimycin Drug Info Phase 3 Pompe's disease [530482]
PAZ-320 Drug Info Phase 2 Type 2 diabetes [524644]
SC-49483 Drug Info Phase 2 Acquired immune deficiency syndrome [521416]
Celgosivir Drug Info Phase 1/2 Dengue fever [545627]
Maltose Drug Info Phase 1/2 Discovery agent [523849]
SALACINOL Drug Info Phase 1/2 Discovery agent [521814]
A-76202M Drug Info Terminated Acquired immune deficiency syndrome [526163]
Inhibitor 1,4-dideoxy-1,4-imino-D-arabinito Drug Info [526274]
2,5-Dideoxy-2,5-imino-D-mannitol Drug Info [526274]
2-Aminomethyl-pyrrolidine-3,4-diol Drug Info [526137]
2-Cyclopentylaminomethyl-pyrrolidine-3,4-diol Drug Info [526137]
3-(4-(4-hydroxyphenyl)phthalazin-1-ylamino)phenol Drug Info [529085]
4'-(p-toluenesulfonamide)-3,4-dihydroxy chalcone Drug Info [527781]
De-O-sulfonated kotalanol Drug Info [531230]
Deoxynojirimycin Drug Info [533823]
Double Oxidized Cysteine Drug Info [551393]
GSC-1 Drug Info [543667]
KOTALANOL Drug Info [531230]
Maltose Drug Info [551391]
Miglitol Drug Info [538156]
Nicotinamide-Adenine-Dinucleotide Drug Info [551393]
PONKORANOL Drug Info [531131]
SALACINOL Drug Info [531230]
SC-49483 Drug Info [534275]
Voglibose Drug Info [537567]
Modulator A-76202M Drug Info [526163]
Acarbose Drug Info [556264]
Alpha-glucosidase Drug Info [543667]
BMN-103 Drug Info [543667]
Celgosivir Drug Info
Imino sugars Drug Info [543667]
PAZ-320 Drug Info [544481]
Rh-alphaglucosidase Drug Info [528715]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Galactose metabolism
Starch and sucrose metabolism
Metabolic pathways
Carbohydrate digestion and absorption
PathWhiz Pathway Starch and Sucrose Metabolism
WikiPathways Metabolism of carbohydrates
References
Ref 468076(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 521416ClinicalTrials.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 521814ClinicalTrials.gov (NCT00306072) Effect of Different Doses of Salacinol Extract on Glycemic and Insulinemic Response in Patients With Type 2 Diabetes. U.S. National Institutes of Health.
Ref 523686ClinicalTrials.gov (NCT01468181) A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
Ref 523849ClinicalTrials.gov (NCT01562626) Phase I/II Study of APS001F With Flucytosine and Maltose in Solid Tumors. U.S. National Institutes of Health.
Ref 524644ClinicalTrials.gov (NCT02060916) Study to Evaluate the Safety and Efficacy of PAZ320 in Patients With Type 2 Diabetes. U.S. National Institutes of Health.
Ref 526163Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D-hexopyranosides. Carbohydr Res. 2001 Oct 15;335(4):283-9.
Ref 530482The 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 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 541872(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 545627Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003977)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 526137Bioorg Med Chem Lett. 2001 Sep 17;11(18):2489-93.Derivatives of (2R,3R,4S)-2-aminomethylpyrrolidine-3,4-diol are selective alpha-mannosidase inhibitors.
Ref 526163Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D-hexopyranosides. Carbohydr Res. 2001 Oct 15;335(4):283-9.
Ref 526274J Nat Prod. 2002 Feb;65(2):198-202.New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii.
Ref 527781Bioorg Med Chem Lett. 2005 Dec 15;15(24):5514-6. Epub 2005 Oct 3.Sulfonamide chalcone as a new class of alpha-glucosidase inhibitors.
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 529085Bioorg Med Chem. 2008 Jan 1;16(1):284-92. Epub 2007 Sep 22.Discovery of novel alpha-glucosidase inhibitors based on the virtual screening with the homology-modeled protein structure.
Ref 531131Bioorg Med Chem Lett. 2010 Oct 1;20(19):5686-9. Epub 2010 Aug 11.Probing the active-site requirements of human intestinal N-terminal maltase glucoamylase: the effect of replacing the sulfate moiety by a methyl ether in ponkoranol, a naturally occurring |A-glucosidase inhibitor.
Ref 531230Bioorg Med Chem. 2010 Nov 15;18(22):7794-8. Epub 2010 Sep 29.Probing the active-site requirements of human intestinal N-terminal maltase-glucoamylase: Synthesis and enzyme inhibitory activities of asix-membered ring nitrogen analogue of kotalanol and its de-O-sulfonated derivative.
Ref 533823J Med Chem. 1994 Oct 28;37(22):3701-6.Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases.
Ref 534275Pathology 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 537567Effects of changeover from voglibose to acarbose on postprandial triglycerides in type 2 diabetes mellitus patients. Adv Ther. 2009 Jun;26(6):660-6. Epub 2009 Jun 30.
Ref 538156Drug therapy of postprandial hyperglycaemia. Drugs. 1999 Jan;57(1):19-29.
Ref 543667(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 544481Treatment 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 551391DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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