THERAPY DOSSIER · th-2c00060e75d7

Eritoran tetrasodium (E5564)

Drug · Toll-like receptor 4/MD-2 antagonist (ANTAGONIST). Competes with LPS for binding to the TLR4 receptor complex, blocking NF-kB activation and production of inflammatory mediators such as TNF-alpha and IL6; binds the hydrophobic pocket of the MD2 portion of the TLR4 complex.

Not approved Suggest a correction

Evidence & regulatory context

Mechanism: Toll-like receptor 4/MD-2 antagonist (ANTAGONIST). Competes with LPS for binding to the TLR4 receptor complex, blocking NF-kB activation and production of inflammatory mediators such as TNF-alpha and IL6; binds the hydrophobic pocket of the MD2 portion of the TLR4 complex.
Target: CHEMBL3038512
Injury models: Haemorrhage/shock
Reported indication: Not recorded
First approval: Not recorded
Development stage: In trials, not approved
ChEMBL record: CHEMBL3301672 ↗
ChEMBL max phase: 3 / 4 (development scale, not regulatory approval)
Synonyms: B-1287; B1287; E-5564; E5564; Eritoran sodium; Eritoran tetrasodium; Eritoran tetrasodium salt
Note: Not recorded

Clinical trials 5

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

NCT02735707 ↗PHASE3recruiting

Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP; includes an Eritoran arm)

Community-acquired Pneumonia · Influenza · COVID-19

Enrolment: 20000 · Results not recorded

NCT00334828 ↗PHASE3completed

ACCESS: A Controlled Comparison of Eritoran Tetrasodium and Placebo in Patients With Severe Sepsis

Severe Sepsis

Enrolment: 2000 · Results not recorded

NCT00046072 ↗PHASE2completed

A Double-Blind, Placebo-Controlled Study of E5564, A Lipid A Antagonist, Administered by Twice Daily Infusions in Patients With Severe Sepsis

Sepsis · Shock, Septic · Sepsis Syndrome · Septicemia · Infection

Enrolment: 300 · Results not recorded

NCT02267317 ↗PHASE2terminated

Phase 2 Study of The Role of Pharmacologic Inhibition of TLR4 With E5564 on Glucose Metabolism in Insulin Resistant Subjects.

Insulin Sensitivity

Enrolment: 15 · Results not recorded

NCT00756912 ↗PHASE1terminated

A Phase I, Open-Label, Dose Escalation Study of Eritoran (E5564) Administered IV Over 14 Days Prior to and During Bone Marrow Engraftment in BMT Patients Who Have Received Myeloablative Conditioning Treatment

Leukemia

Enrolment: 30 · Results not recorded

Preclinical evidence 1

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

PMID 24569510 ↗2014Reported benefit

Toll-like receptor 4 plays a central role in cardiac dysfunction during trauma hemorrhage shock.

MouseHaemorrhage/shockControlledC57BL/10ScCr (TLR4-deficient) and C57BL/10ScSn (wild type)Malen = TLR4-deficient trauma-haemorrhage n = 7 per group; wild typ…0.3, 1.0, 3.0, 5.0 and 10.0 mg/kg body weight, given as a s…Single bolus at the initiation of haemorrhage

Model: Trauma-haemorrhage: soft tissue injury (cervical incision and left thoracotomy) with blood withdrawal from the jugular vein at 0.82 mL/10 min/30 g until mean arterial pressure reached 35 plus or minus 5 mmHg, maintained for the first 10 min, with cardiac function recorded to 60 min

Trauma-haemorrhage reduced left ventricular pressure by 35.4% and dP/dtmax by 52.9% in wild type mice but not in TLR4-deficient mice. Eritoran at 1, 3, 5 and 10 mg/kg significantly attenuated cardiac dysfunction, with 3 mg/kg giving the greatest effect; 0.3 mg/kg was not significant. TLR4 deficienc…

Extraction: extract · Subtype source: llm · Supplied extraction confidence: 0.92. Machine-extracted fields require source verification.

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