Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLOHU4)

• DTT Name: Mycobacterium Decaprenylphosphoryl-beta-D-ribose oxidase (McyB dprE1)
• Synonyms: FAD-dependent decaprenylphosphoryl-beta-D-ribofuranose 2-oxidase; Decaprenylphosphoryl-beta-D-ribose oxidase; Decaprenylphosphoryl-beta-D-ribose 2-epimerase flavoprotein subunit; Decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase; Decaprenylphosphoryl-beta-D-ribofuranose 2'-epimerase subunit DprE1; Decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase; Decaprenyl-phosphoribose 2'-epimerase subunit 1
• Gene Name: McyB dprE1
• DTT Type: Clinical trial target; [1]
• UniProt ID: DPRE1_MYCTU
• TTD ID: T59554
• EC Number: EC 1.1.98.3
• Sequence:
  MLSVGATTTATRLTGWGRTAPSVANVLRTPDAEMIVKAVARVAESGGGRGAIARGLGRSY
  GDNAQNGGGLVIDMTPLNTIHSIDADTKLVDIDAGVNLDQLMKAALPFGLWVPVLPGTRQ
  VTVGGAIACDIHGKNHHSAGSFGNHVRSMDLLTADGEIRHLTPTGEDAELFWATVGGNGL
  TGIIMRATIEMTPTSTAYFIADGDVTASLDETIALHSDGSEARYTYSSAWFDAISAPPKL
  GRAAVSRGRLATVEQLPAKLRSEPLKFDAPQLLTLPDVFPNGLANKYTFGPIGELWYRKS
  GTYRGKVQNLTQFYHPLDMFGEWNRAYGPAGFLQYQFVIPTEAVDEFKKIIGVIQASGHY
  SFLNVFKLFGPRNQAPLSFPIPGWNICVDFPIKDGLGKFVSELDRRVLEFGGRLYTAKDS
  RTTAETFHAMYPRVDEWISVRRKVDPLRVFASDMARRLELL
• Function: Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans. DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex. Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in vitro. Appears to be essential for the growth and survival of M.tuberculosis.
• BioCyc Pathway: MetaCyc:G185E-8086-MON

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BTZ-043	DMVXBSW	Tuberculosis	1B10-1B14	Phase 2	[2]
TBA-7371	DMZTOJ6	Tuberculosis	1B10-1B14	Phase 2	[3]
OPC-167832	DMZB6LO	Tuberculosis	1B10-1B14	Phase 1/2	[4]
Macozinone	DM0HKU7	Mycobacterium infection	1B10-1B21	Phase 1	[5]

References

• [1] Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1): challenging target for antitubercular drug discovery. Chem Cent J. 2018 Jun 23;12(1):72.
• [2] Clinical pipeline report, company report or official report of TB
• [3] Clinical pipeline report, company report or official report of TB Alliance.
• [4] OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor. Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.
• [5] Spirocyclic and Bicyclic 8-Nitrobenzothiazinones for Tuberculosis with Improved Physicochemical and Pharmacokinetic Properties. ACS Med Chem Lett. 2019 Feb 23;10(3):348-351.