THERAPY DOSSIER · th-ecf0dda60394

TLR5 neutralising antibody; genetic TLR5 deletion; AAV9-shNOX2; AAV9-TLR5 rescue; flagellin as TLR5 agonist; in vitro siTLR5, siNOX2, siSyk, GSK2795039, piceatannol, SB203580

Biologic · Composite preclinical toolkit (neutralising antibody, AAV vectors, siRNA and tool compounds GSK2795039 (NOX2 inhibitor), piceatannol (Syk inhibitor) and SB203580 (p38 MAPK inhibitor)). No single ChEMBL drug entity applies and no human trial exists for the TLR5-directed intervention; left unresolved rather than resolving on an arbitrary component.

Non-drug Suggest a correction

Evidence & regulatory context

Mechanism: Composite preclinical toolkit (neutralising antibody, AAV vectors, siRNA and tool compounds GSK2795039 (NOX2 inhibitor), piceatannol (Syk inhibitor) and SB203580 (p38 MAPK inhibitor)). No single ChEMBL drug entity applies and no human trial exists for the TLR5-directed intervention; left unresolved rather than resolving on an arbitrary component.
Target: Not recorded
Injury models: Chemical/toxin
Reported indication: Not recorded
First approval: Not recorded
Development stage: Not recorded
ChEMBL record: Not recorded
ChEMBL max phase: Not recorded
Synonyms: Not recorded
Note: Not recorded

Clinical trials 0

0 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

No linked human trial in this dataset.

Preclinical evidence 1

1 studies reported at therapy level; 1 evidence entries itemised.

PMID 33042267 ↗2020Reported benefit

Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice.

MixedChemical/toxinGlobal TLR5 knockout mice on C57BL/6 background and age-matched wild-type littermates; AAV9-shNOX2 for NOX2 knockdownMale for flagellin experiments; not stated for remaining in vivo experimentsDoxorubicin intraperitoneal; AAV9 vectors intravenous; flagellin intravenous; route of neutralising antibody not statedTLR5 neutralising antibody 5 microgram per mouse in 100 mic…Neutralising antibody or isotype IgG given at the same time as doxorubicin; AAV…

Model: Doxorubicin-induced acute cardiotoxicity: single intraperitoneal doxorubicin 15 mg/kg with sacrifice at 3 days, plus a 7-day survival experiment; in vitro neonatal rat cardiomyocytes exposed to doxorubicin 1 microM for 24 h

TLR5 expression rose after doxorubicin. TLR5 knockout attenuated weight loss, preserved heart weight to tibia length and ejection fraction, lowered CK-MB and LDH, and reduced superoxide, 4-HNE, MDA, NADPH oxidase activity, NOX2, TNF-alpha, IL-1beta, NF-kappaB translocation, Bax and TUNEL positivity…

Extraction: extract · Supplied extraction confidence: 0.8. Machine-extracted fields require source verification.

Loading the evidence…

TLR5 neutralising antibody; genetic TLR5 deletion; AAV9-shNOX2; AAV9-TLR5 rescue; flagellin as TLR5 agonist; in vitro siTLR5, siNOX2, siSyk, GSK2795039, piceatannol, SB203580