Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Intestinal maltase-glucoamylase (MGAM)
• Synonyms: MGAM
• Gene Name: MGAM
• DTT Type: Successful target; [1]
• BioChemical Class: Glycosylase
• UniProt ID: MGA_HUMAN
• TTD ID: T92777
• 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
• 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.
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
  Carbohydrate digestion and absorption (hsa04973)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Digestion of dietary carbohydrate (R-HSA-189085)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acarbose	DMRM3AW	Diabetic complication	5A2Y	Approved	[2]
Miglitol	DMXBQAM	Diabetic complication	5A2Y	Approved	[3]
Rh-alphaglucosidase	DMNF0G8	Pompe disease	5C51.3	Approved	[4]
Voglibose	DMUBP9O	Diabetic complication	5A2Y	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha-glucosidase	DM2RTGP	Muscle disease	FB3Z	Phase 3	[5]
Deoxynojirimycin	DM2ATZB	Pompe disease	5C51.3	Phase 3	[6]
PAZ-320	DMU0812	Type-2 diabetes	5A11	Phase 2	[7]
SC-49483	DM180VX	Acquired immune deficiency syndrome	1C62.3	Phase 2	[8]
Celgosivir	DMD1V7I	Dengue fever	1D2Z	Phase 1/2	[9]
Maltose	DMH0ROP	N. A.	N. A.	Phase 1/2	[10]
SALACINOL	DMVKQT8	N. A.	N. A.	Phase 1/2	[11]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-76202M	DMRHEWX	Acquired immune deficiency syndrome	1C62.3	Terminated	[12]

14 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,4-dideoxy-1,4-imino-D-arabinito	DMB5VQK	Discovery agent	N.A.	Investigative	[13]
2,5-Dideoxy-2,5-imino-D-mannitol	DMGQVF5	Discovery agent	N.A.	Investigative	[13]
2-Aminomethyl-pyrrolidine-3,4-diol	DMAN8EH	Discovery agent	N.A.	Investigative	[14]
2-Cyclopentylaminomethyl-pyrrolidine-3,4-diol	DMS947W	Discovery agent	N.A.	Investigative	[14]
3-(4-(4-hydroxyphenyl)phthalazin-1-ylamino)phenol	DM1GVE8	Discovery agent	N.A.	Investigative	[15]
4'-(p-toluenesulfonamide)-3,4-dihydroxy chalcone	DM8M0N9	Discovery agent	N.A.	Investigative	[16]
BMN-103	DMYWEO6	Pompe disease	5C51.3	Investigative	[5]
De-O-sulfonated kotalanol	DMNWRV9	Discovery agent	N.A.	Investigative	[11]
Double Oxidized Cysteine	DM6TU84	Discovery agent	N.A.	Investigative	[17]
GSC-1	DMTKGA3	Hyperglycemia	MA18.0	Investigative	[5]
Imino sugars	DMSINGH	Dengue fever	1D2Z	Investigative	[5]
KOTALANOL	DMT1H9Z	Discovery agent	N.A.	Investigative	[11]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[17]
PONKORANOL	DMGRPK8	Discovery agent	N.A.	Investigative	[18]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	4.59E-01	-0.02	-0.24

References

• [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.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Drug therapy of postprandial hyperglycaemia. Drugs. 1999 Jan;57(1):19-29.
• [4] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [5] 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).
• [6] Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases. J Med Chem. 1994 Oct 28;37(22):3701-6.
• [7] 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.
• [8] 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.
• [9] Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection.Curr Opin Investig Drugs.2009 Aug;10(8):860-70.
• [10] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [11] 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.
• [12] Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D-hexopyranosides. Carbohydr Res. 2001 Oct 15;335(4):283-9.
• [13] New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii. J Nat Prod. 2002 Feb;65(2):198-202.
• [14] 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.
• [15] 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.
• [16] Sulfonamide chalcone as a new class of alpha-glucosidase inhibitors. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5514-6.
• [17] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] 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.