THERAPY DOSSIER · th-b24568dbf74c

CLI-095 (specific Toll-like receptor 4 inhibitor)

Drug · Toll-like receptor 4 (TLR4) inhibitor (INHIBITOR)

Evidence & regulatory context

Mechanism: Toll-like receptor 4 (TLR4) inhibitor (INHIBITOR)
Target: CHEMBL5255
Injury models: Ischaemia-reperfusion · Crush · TBI
Reported indication: Not recorded
First approval: Not recorded
Development stage: In trials, not approved
ChEMBL record: CHEMBL225157 ↗
ChEMBL max phase: 3 / 4 (development scale, not regulatory approval)
Synonyms: Resatorvid; CLI-095; TAK-242
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.

NCT00143611 ↗PHASE3completed

Pivotal Study of TAK-242 (resatorvid) in Adults With Severe Sepsis

Sepsis

Enrolment: 277 · Results not recorded

NCT00633477 ↗PHASE3terminated

TAK-242 vs Placebo in Sepsis-Induced Cardiovascular and Respiratory Failure

Sepsis

Enrolment: 18 · Results not recorded

NCT06890039 ↗PHASE2not yet recruiting

Phase II, Double-blind, Randomized, Placebo-controlled, Multicentre Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of TAK-242 and (G-CSF) in Subjects With (sAH) and (ACLF)

Acute-On-Chronic Liver Failure · Alcoholic Hepatitis · Liver Cirrhosis, Alcoholic

Enrolment: 78 · Results not recorded

NCT04620148 ↗PHASE2unknown

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Proof-of-Concept, Phase 2a Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous TAK-242 in Subjects With Acute Alcoholic Hepatitis Causing Decompensation of Alcohol-related Cirrhosis and Acute-on-Chronic Liver Failure

Acute-On-Chronic Liver Failure

Enrolment: 100 · Results not recorded

NCT07092215 ↗EARLY_PHASE1completed

Mechanisms of Pain Hypersensitivity in a Human Skin Inflammation Model - A Double-blind, Randomized, Placebo-controlled Crossover Study

Pain

Enrolment: 42 · Results not recorded

Preclinical evidence 3

3 studies reported at therapy level; 3 evidence entries itemised.

PMID 22363055 ↗2012Reported benefit

Alternatively-spliced extra domain A of fibronectin promotes acute inflammation and brain injury after cerebral ischemia in mice.

MouseIschaemia-reperfusionCerebral (MCAO/stroke)EDA+/+ and EDA+/- mice backcrossed more than 15 generations onto C57BL/6J; wild-type C57BL/6J controlsMaleIntravenous1 mg/kg30 min before the onset of ischaemia

Model: Focal cerebral ischaemia by 1 h middle cerebral artery occlusion with 23 h reperfusion

EDA-containing fibronectin worsened infarct size and inflammation, and the Toll-like receptor 4 inhibitor largely abrogated the increased brain injury and neurological deficits in EDA+/+ mice.

Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.85. Machine-extracted fields require source verification.

PMID 32967743 ↗2020Reported benefit

TAK-242 Attenuates Crush Injury Induced Acute Kidney Injury through Inhibiting TLR4/NF-kB Signaling Pathways in Rats.

RatCrushLimb / muscle crushWistarMalen = Part 1: 50 rats, n = 10 per group across control and four c…

Model: Crush injury induced acute kidney injury produced by applying 3 kg pressure for eight hours, with sacrifice at 0, 6, 12 and 24 hours after relief of pressure

Crush injury damaged kidney tissue and raised serum creatinine, blood urea nitrogen, myoglobin, potassium, interleukin-6, tumour necrosis factor alpha and TLR4 mRNA, most markedly at 12 hours. TAK-242 significantly reduced kidney tissue damage and all of these markers together with TLR4 and P65 pro…

Extraction: extract · Subtype source: llm · Supplied extraction confidence: 0.75. Machine-extracted fields require source verification.

PMID 25497689 ↗2014Mixed findings

Toll-like receptor 4 enhancement of non-NMDA synaptic currents increases dentate excitability after brain injury.

MixedTBIFluid percussionWistar; C57Bl6 wild-type and TLR4 knockout mice for controlsMale rats; mouse sex not statedn = Western blot n=6 rats per group; field recordings 9 slices…Ex vivo bath incubation of acute hippocampal slicesLPS-RS reported as 50 ng/mL in methods and 50 micrograms/mL…Slices prepared 3 to 5 days or 7 to 9 days after injury, with drug applied afte…

Model: Moderate lateral fluid percussion injury at 2 to 2.2 atm delivered through a 3 mm left craniotomy with intact dura; sham animals attached to the device without pendulum drop

One week after fluid percussion injury TLR4 antagonism reduced dentate population spike amplitude and non-NMDA EPSC amplitude and charge in granule and mossy cells, while the same antagonist increased excitability in sham controls, indicating bidirectional TLR4 modulation with no effect on NMDA cur…

Extraction: extract · Subtype source: rule · Supplied extraction confidence: 0.9. Machine-extracted fields require source verification.

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