Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZMS1L)

• DTT Name: Fungal Papulacandin B resistance protein 1 (Fung FKS1)
• Synonyms: UDP-glucose-1,3-beta-D-glucan glucosyltransferase; Papulacandin B sensitivity protein 1 of Saccharomyces cerevisiae; Glucan synthase; FKS1 protein of Saccharomyces cerevisiae; FKS1; CWN53 protein of Saccharomyces cerevisiae; CND1 protein of Saccharomyces cerevisiae; Beta-1,3-glucan synthetase; Beta-1,3-glucan synthase; 1,3-beta-D-glucan-UDP glucosyltransferase of Saccharomyces cerevisiae; (1,3)-beta-D-glucan synthase
• Gene Name: Fung FKS1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Hexosyltransferase
• UniProt ID: FKS1_YEAST
• TTD ID: T40785
• EC Number: EC 2.4.1.34
• Sequence:
  MNTDQQPYQGQTDYTQGPGNGQSQEQDYDQYGQPLYPSQADGYYDPNVAAGTEADMYGQQ
  PPNESYDQDYTNGEYYGQPPNMAAQDGENFSDFSSYGPPGTPGYDSYGGQYTASQMSYGE
  PNSSGTSTPIYGNYDPNAIAMALPNEPYPAWTADSQSPVSIEQIEDIFIDLTNRLGFQRD
  SMRNMFDHFMVLLDSRSSRMSPDQALLSLHADYIGGDTANYKKWYFAAQLDMDDEIGFRN
  MSLGKLSRKARKAKKKNKKAMEEANPEDTEETLNKIEGDNSLEAADFRWKAKMNQLSPLE
  RVRHIALYLLCWGEANQVRFTAECLCFIYKCALDYLDSPLCQQRQEPMPEGDFLNRVITP
  IYHFIRNQVYEIVDGRFVKRERDHNKIVGYDDLNQLFWYPEGIAKIVLEDGTKLIELPLE
  ERYLRLGDVVWDDVFFKTYKETRTWLHLVTNFNRIWVMHISIFWMYFAYNSPTFYTHNYQ
  QLVDNQPLAAYKWASCALGGTVASLIQIVATLCEWSFVPRKWAGAQHLSRRFWFLCIIFG
  INLGPIIFVFAYDKDTVYSTAAHVVAAVMFFVAVATIIFFSIMPLGGLFTSYMKKSTRRY
  VASQTFTAAFAPLHGLDRWMSYLVWVTVFAAKYSESYYFLVLSLRDPIRILSTTAMRCTG
  EYWWGAVLCKVQPKIVLGLVIATDFILFFLDTYLWYIIVNTIFSVGKSFYLGISILTPWR
  NIFTRLPKRIYSKILATTDMEIKYKPKVLISQVWNAIIISMYREHLLAIDHVQKLLYHQV
  PSEIEGKRTLRAPTFFVSQDDNNFETEFFPRDSEAERRISFFAQSLSTPIPEPLPVDNMP
  TFTVLTPHYAERILLSLREIIREDDQFSRVTLLEYLKQLHPVEWECFVKDTKILAEETAA
  YEGNENEAEKEDALKSQIDDLPFYCIGFKSAAPEYTLRTRIWASLRSQTLYRTISGFMNY
  SRAIKLLYRVENPEIVQMFGGNAEGLERELEKMARRKFKFLVSMQRLAKFKPHELENAEF
  LLRAYPDLQIAYLDEEPPLTEGEEPRIYSALIDGHCEILDNGRRRPKFRVQLSGNPILGD
  GKSDNQNHALIFYRGEYIQLIDANQDNYLEECLKIRSVLAEFEELNVEQVNPYAPGLRYE
  EQTTNHPVAIVGAREYIFSENSGVLGDVAAGKEQTFGTLFARTLSQIGGKLHYGHPDFIN
  ATFMTTRGGVSKAQKGLHLNEDIYAGMNAMLRGGRIKHCEYYQCGKGRDLGFGTILNFTT
  KIGAGMGEQMLSREYYYLGTQLPVDRFLTFYYAHPGFHLNNLFIQLSLQMFMLTLVNLSS
  LAHESIMCIYDRNKPKTDVLVPIGCYNFQPAVDWVRRYTLSIFIVFWIAFVPIVVQELIE
  RGLWKATQRFFCHLLSLSPMFEVFAGQIYSSALLSDLAIGGARYISTGRGFATSRIPFSI
  LYSRFAGSAIYMGARSMLMLLFGTVAHWQAPLLWFWASLSSLIFAPFVFNPHQFAWEDFF
  LDYRDYIRWLSRGNNQYHRNSWIGYVRMSRARITGFKRKLVGDESEKAAGDASRAHRTNL
  IMAEIIPCAIYAAGCFIAFTFINAQTGVKTTDDDRVNSVLRIIICTLAPIAVNLGVLFFC
  MGMSCCSGPLFGMCCKKTGSVMAGIAHGVAVIVHIAFFIVMWVLESFNFVRMLIGVVTCI
  QCQRLIFHCMTALMLTREFKNDHANTAFWTGKWYGKGMGYMAWTQPSRELTAKVIELSEF
  AADFVLGHVILICQLPLIIIPKIDKFHSIMLFWLKPSRQIRPPIYSLKQTRLRKRMVKKY
  CSLYFLVLAIFAGCIIGPAVASAKIHKHIGDSLDGVVHNLFQPINTTNNDTGSQMSTYQS
  HYYTHTPSLKTWSTIK
• 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:YLR342W-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilofungin	DMBNWM1	Candidiasis	1F23	Terminated	[2]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACULEACIN A	DMR2MUG	Discovery agent	N.A.	Investigative	[3]
L-692289	DMAB1RW	Discovery agent	N.A.	Investigative	[4]
Pyridobenzimidazole	DM3PAS4	Fungal infection	1F29-1F2F	Investigative	[5]

References

• [1] Pfizer. Product Development Pipeline. March 31 2009.
• [2] Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins. Antimicrob Agents Chemother. 2005 Jul;49(7):2851-6.
• [3] Synthesis, anti-fungal and 1,3--D-glucan synthase inhibitory activities of caffeic and quinic acid derivatives. Bioorg Med Chem. 2010 Oct 1;18(19):7009-14.
• [4] Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives, Bioorg. Med. Chem. Lett. 5(20):2357-2362 (1995).
• [5] Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.