Target Information

Target General Infomation
Target ID
T40785
Former ID
TTDS00299
Target Name
1,3-Beta-Glucan synthase
Gene Name
FKS1
Synonyms
(1,3)-beta-D-glucan synthase; 1,3-beta-D-glucan-UDP glucosyltransferase; Beta-1,3-glucan synthase; Beta-1,3-glucan synthetase; CND1 protein; CWN53 protein; FKS1 protein; Glucan synthase; Papulacandin B sensitivity protein 1; UDP-glucose-1,3-beta-D-glucan glucosyltransferase; FKS1
Target Type
Clinical Trial
Disease Candidiasis infection [ICD9: 001-139, 112; ICD10: B37]
Fungal infections [ICD9: 110-118; ICD10: B35-B49]
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.
BioChemical Class
Hexosyltransferase
Target Validation
T40785
UniProt ID
P38631
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
Drugs and Mode of Action
Drug(s) Eraxis/Vfend Drug Info Phase 3 Fungal infections [550062]
Cilofungin Drug Info Terminated Candidiasis infection [551808]
Inhibitor ACULEACIN A Drug Info [531145]
Cilofungin Drug Info [536106], [537906], [537941]
Eraxis/Vfend Drug Info [549974], [550694]
L-692289 Drug Info [551287]
Macrocyclic lipopeptidolactone derivative Drug Info [525982]
Pyridobenzimidazole Drug Info [537364]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
Pathways
KEGG Pathway Starch and sucrose metabolism
MAPK signaling pathway - yeast
References
Ref 550062Clinical pipeline report, company report or official report of Pfizer.
Ref 551808Fungi: Biology and Applications, Kevin Kavanagh. Page(211).
Ref 525982Bioorg Med Chem Lett. 2001 Feb 12;11(3):395-8.Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.
Ref 531145Bioorg Med Chem. 2010 Oct 1;18(19):7009-14. Epub 2010 Aug 13.Synthesis, anti-fungal and 1,3-|A-D-glucan synthase inhibitory activities of caffeic and quinic acid derivatives.
Ref 536106Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins. Antimicrob Agents Chemother. 2005 Jul;49(7):2851-6.
Ref 537364Novel 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. Epub 2009 May 7.
Ref 537906Characterization and cilofungin inhibition of solubilized Aspergillus fumigatus (1,3)-beta-D-glucan synthase. Antimicrob Agents Chemother. 1994 May;38(5):937-44.
Ref 537941Correlation of cilofungin in vivo efficacy with its activity against Aspergillus fumigatus (1,3)-beta-D-glucan synthase. FEMS Microbiol Lett. 1993 Apr 1;108(2):133-7.
Ref 549974Pfizer. Product Development Pipeline. March 31 2009.
Ref 550694Eraxis. News for Eraxis. 2008. eduDrugs.
Ref 551287Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives, Bioorg. Med. Chem. Lett. 5(20):2357-2362 (1995).

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