Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0SFXH)

• DTT Name: Fungal 1,3-beta-glucan synthase (Fung GSC2)
• Synonyms: GSC2
• Gene Name: Fung GSC2
• DTT Type: Successful target; [1]
• BioChemical Class: Hexosyltransferase
• UniProt ID: FKS2_YEAST
• TTD ID: T73189
• EC Number: EC 2.4.1.34
• Sequence:
  MSYNDPNLNGQYYSNGDGTGDGNYPTYQVTQDQSAYDEYGQPIYTQNQLDDGYYDPNEQY
  VDGTQFPQGQDPSQDQGPYNNDASYYNQPPNMMNPSSQDGENFSDFSSYGPPSGTYPNDQ
  YTPSQMSYPDQDGSSGASTPYGNGVVNGNGQYYDPNAIEMALPNDPYPAWTADPQSPLPI
  EQIEDIFIDLTNKFGFQRDSMRNMFDHFMTLLDSRSSRMSPEQALLSLHADYIGGDTANY
  KKWYFAAQLDMDDEIGFRNMKLGKLSRKARKAKKKNKKAMQEASPEDTEETLNQIEGDNS
  LEAADFRWKSKMNQLSPFEMVRQIALFLLCWGEANQVRFTPECLCFIYKCASDYLDSAQC
  QQRPDPLPEGDFLNRVITPLYRFIRSQVYEIVDGRYVKSEKDHNKVIGYDDVNQLFWYPE
  GIAKIVMEDGTRLIDLPAEERYLKLGEIPWDDVFFKTYKETRSWLHLVTNFNRIWIMHIS
  VYWMYCAYNAPTFYTHNYQQLVDNQPLAAYKWATAALGGTVASLIQVAATLCEWSFVPRK
  WAGAQHLSRRFWFLCVIMGINLGPVIFVFAYDKDTVYSTAAHVVGAVMFFVAVATLVFFS
  VMPLGGLFTSYMKKSTRSYVASQTFTASFAPLHGLDRWMSYLVWVTVFAAKYAESYFFLI
  LSLRDPIRILSTTSMRCTGEYWWGNKICKVQPKIVLGLMIATDFILFFLDTYLWYIVVNT
  VFSVGKSFYLGISILTPWRNIFTRLPKRIYSKILATTDMEIKYKPKVLISQIWNAIIISM
  YREHLLAIDHVQKLLYHQVPSEIEGKRTLRAPTFFVSQDDNNFETEFFPRDSEAERRISF
  FAQSLSTPIPEPLPVDNMPTFTVLTPHYAERILLSLREIIREDDQFSRVTLLEYLKQLHP
  VEWDCFVKDTKILAEETAAYENNEDEPEKEDALKSQIDDLPFYCIGFKSAAPEYTLRTRI
  WASLRSQTLYRTISGFMNYSRAIKLLYRVENPEIVQMFGGNADGLERELEKMARRKFKFL
  VSMQRLAKFKPHELENAEFLLRAYPDLQIAYLDEEPPLNEGEEPRIYSALIDGHCEILEN
  GRRRPKFRVQLSGNPILGDGKSDNQNHALIFYRGEYIQLIDANQDNYLEECLKIRSVLAE
  FEELGIEQIHPYTPGLKYEDQSTNHPVAIVGAREYIFSENSGVLGDVAAGKEQTFGTLFA
  RTLAQIGGKLHYGHPDFINATFMTTRGGVSKAQKGLHLNEDIYAGMNAVLRGGRIKHCEY
  YQCGKGRDLGFGTILNFTTKIGAGMGEQMLSREYYYLGTQLPIDRFLTFYYAHPGFHLNN
  LFIQLSLQMFMLTLVNLHALAHESILCVYDRDKPITDVLYPIGCYNFHPAIDWVRRYTLS
  IFIVFWIAFVPIVVQELIERGLWKATQRFFRHILSLSPMFEVFAGQIYSSALLSDIAVGG
  ARYISTGRGFATSRIPFSILYSRFAGSAIYMGSRSMLMLLFGTVAHWQAPLLWFWASLSA
  LIFAPFIFNPHQFAWEDFFLDYRDYIRWLSRGNNKYHRNSWIGYVRMSRSRVTGFKRKLV
  GDESEKSAGDASRAHRTNLIMAEIIPCAIYAAGCFIAFTFINAQTGVKTTDEDRVNSTLR
  IIICTLAPIVIDIGVLFFCMGLSCCSGPLLGMCCKKTGSVMAGIAHGIAVVVHIVFFIVM
  WVLEGFSFVRMLIGVVTCIQCQRLIFHCMTVLLLTREFKNDHANTAFWTGKWYSTGLGYM
  AWTQPTRELTAKVIELSEFAADFVLGHVILIFQLPVICIPKIDKFHSIMLFWLKPSRQIR
  PPIYSLKQARLRKRMVRRYCSLYFLVLIIFAGCIVGPAVASAHVPKDLGSGLTGTFHNLV
  QPRNVSNNDTGSQMSTYKSHYYTHTPSLKTWSTIK
• Function: Alternate catalytic subunit of the 1,3-beta-glucan synthase (GS). Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling.
• KEGG Pathway:
  Starch and sucrose metabolism (sce00500)
  MAPK signaling pathway - yeast (sce04011)
• BioCyc Pathway: YEAST:YGR032W-MON

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anidulafungin	DM8QM5U	Aspergillosis	1F20	Approved	[2]
Caspofungin	DMGQIPT	Candidiasis	1F23	Approved	[1]
Ibrexafungerp	DMK1IPV	Vulvovaginal Candidiasis	1F23.10	Approved	[3]
Micafungin	DM6Y3AN	Aspergillosis	1F20	Approved	[4]
Rezafungin	DMQ4CSX	Candidiasis	1F23	Approved	[5]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-733560	DMYZPJU	Aspergillosis	1F20	Terminated	[6]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [3] Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model. Antimicrob Agents Chemother. 2015 Feb;59(2):1265-72.
• [4] An immunomodulatory activity of micafungin in preclinical aspergillosis. J Antimicrob Chemother. 2014 Apr;69(4):1065-74.
• [5] Antifungal drugs: What brings the future?. Med Mycol. 2019 Jun 1;57(Supplement_3):S328-S343.
• [6] Discovery of Novel Antifungal (1,3)--d-Glucan Synthase Inhibitors