Target Information

Target General Information

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Target ID

T72545 (Former ID: TTDR01169)

Target Name

Bacterial DNA topoisomerase 4A (Bact parC)

Synonyms

parC; Topoisomerase IV subunit A of Escherichia coli

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Gene Name

Bact parC

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Urinary tract infection [ICD-11: GC08]

Function

Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule. MukB stimulates the relaxation activity of topoisomeraseIV and also has a modest effect on decatenation.

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BioChemical Class

Topoisomerase GyrA ParC

UniProt ID

PARC_ECOLI

EC Number

EC 5.6.2.3

Sequence

MSDMAERLALHEFTENAYLNYSMYVIMDRALPFIGDGLKPVQRRIVYAMSELGLNASAKF
KKSARTVGDVLGKYHPHGDSACYEAMVLMAQPFSYRYPLVDGQGNWGAPDDPKSFAAMRY
TESRLSKYSELLLSELGQGTADWVPNFDGTLQEPKMLPARLPNILLNGTTGIAVGMATDI
PPHNLREVAQAAIALIDQPKTTLDQLLDIVQGPDYPTEAEIITSRAEIRKIYENGRGSVR
MRAVWKKEDGAVVISALPHQVSGARVLEQIAAQMRNKKLPMVDDLRDESDHENPTRLVIV
PRSNRVDMDQVMNHLFATTDLEKSYRINLNMIGLDGRPAVKNLLEILSEWLVFRRDTVRR
RLNYRLEKVLKRLHILEGLLVAFLNIDEVIEIIRNEDEPKPALMSRFGLTETQAEAILEL
KLRHLAKLEEMKIRGEQSELEKERDQLQGILASERKMNNLLKKELQADAQAYGDDRRSPL
QEREEAKAMSEHDMLPSEPVTIVLSQMGWVRSAKGHDIDAPGLNYKAGDSFKAAVKGKSN
QPVVFVDSTGRSYAIDPITLPSARGQGEPLTGKLTLPPGATVDHMLMESDDQKLLMASDA
GYGFVCTFNDLVARNRAGKALITLPENAHVMPPVVIEDASDMLLAITQAGRMLMFPVSDL
PQLSKGKGNKIINIPSAEAARGEDGLAQLYVLPPQSTLTIHVGKRKIKLRPEELQKVTGE
RGRRGTLMRGLQRIDRVEIDSPRRASSGDSEE

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3D Structure

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PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Prulifloxacin

Drug Info

Approved

Urinary tract infection

[2]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

Pazufloxacin

Drug Info

Phase 3

Conjunctivitis

[3]

JNJ-32729463

Drug Info

Phase 2

Community-acquired pneumonia

[4]

Sitafloxacin

Drug Info

Phase 2

Escherichia coli infection

[5]

TNP-2092

Drug Info

Phase 2

Skin and skin-structure infection

[6]

VB 1953

Drug Info

Phase 2

Acne vulgaris

[7]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 7 Inhibitor drugs

Prulifloxacin

Drug Info

[2]

Pazufloxacin

Drug Info

[8]

JNJ-32729463

Drug Info

[9]

Sitafloxacin

Drug Info

[10]

TNP-2092

Drug Info

[11]

VB 1953

Drug Info

[12]

A-62824

Drug Info

[1]

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Similarity Proteins

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Similarity Proteins

There is no similarity protein (E value < 0.005) for this target

Chemical Structure based Activity Landscape of Target

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Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Isothiazoloquinolones containing functionalized aromatic hydrocarbons at the 7-position: synthesis and in vitro activity of a series of potent anti... Bioorg Med Chem Lett. 2006 Mar 1;16(5):1272-6.

REF 2

Prulifloxacin: a new antibacterial fluoroquinolone. Expert Rev Anti Infect Ther. 2006 Feb;4(1):27-41.

REF 3

ClinicalTrials.gov (NCT03696342) Efficacy of the Ophthalmic Pazufloxacin 0.6% for Bacterial Conjunctivitis, Compared to Gatifloxacin 0.3%. (PRO-157). U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT01198626) Efficacy and Safety Study of JNJ-32729463 Compared With Moxifloxacin for the Treatment of Subjects Requiring Hospitalization for Community-Acquired Bacterial Pneumonia. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT02537847) Sitafloxacin and Ertapenem Treatment for Acute Pyelonephritis Caused by Escherichia Coli (SETAP). U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT03964493) TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection (P2_ABSSSI). U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT03900676) Efficacy and Safety Study of VB-1953 Topical Gel for Inflammatory Facial Acne Vulgaris. U.S. National Institutes of Health.

REF 8

Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition. Antimicrob Agents Chemother. 2001 Dec;45(12):3544-7.

REF 9

Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011 Dec;55(12):5512-21.

REF 10

Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother. 2008 Jul;62(1):98-104.

REF 11

Clinical pipeline report, company report or official report of TenNor Therapeutics.

REF 12

Clinical pipeline report, company report or official report of Vyome Therapeutics.

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