Ibudilast

• CAS: 50847-11-5
• Catalog Number: ACM50847115
• Category: Main Products
• Molecular Weight: 230.31
• Molecular Formula: C₁₄H₁₈N₂O
• Synonyms: IBUDILAST;IBUDILAST-D7;KC-404;1-PROPANONE, 2-METHYL-1-[2-(1-METHYLETHYL)PYRAZOLO[1,5-A]PYRIDIN-3-YL];2-isopropyl-3-isobutyrylpyrazolo[1,5-a]pyridine;2-METHYL-1-[2-(1-METHYLETHYL)PYRAZOLO[1,5-A]PYRIDIN-3-YL]-1-PROPANONE;3-ISOBUTYRYL-2-ISOPROPYLPYRAZOLO(1,5-A)PYRIDINE;2-methyl-1-(2-(1-methylethyl)pyrazolo(1,5-a)pyridin-3-yl)-1-propanon
• IUPAC Name: 2-methyl-1-(2-propan-2-ylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one
• Canonical SMILES: CC(C)C1=NN2C=CC=CC2=C1C(=O)C(C)C
• InChI Key: ZJVFLBOZORBYFE-UHFFFAOYSA-N
• Melting Point: 53-54°C
• Density: 1.09
• Appearance: solid
• Exact Mass: 230.14200
• Hazard Statements: Xn
• Safety Description: 26-36
• Supplemental Hazard Statements: H302-H315-H319-H335
• Symbol: GHS07
• WGK Germany: 3

Case Study

Ibudilast for Alleviating ASD-like Symptoms in a Prenatal Valproic Acid Exposure Model

Sandhu A, et al. Brain Research, 2023, 1815, 148443.

In this study, ibudilast was experimentally evaluated for its therapeutic potential in autism spectrum disorder (ASD) using a well-established prenatal valproic acid (VPA) rat model. Pregnant Wistar rats received VPA (600 mg/kg, i.p.) on embryonic day 12.5 to induce ASD-like phenotypes in offspring. Male pups were administered ibudilast intraperitoneally at doses of 5 or 10 mg/kg during the postnatal period. Behavioral assays assessed core ASD-related symptoms, including deficits in social interaction, impaired spatial memory (Morris water maze), heightened anxiety (elevated plus maze), altered locomotion, and pain sensitivity. Biochemical evaluations involved quantifying oxidative stress markers and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in the hippocampus. Immunohistochemical analysis measured GFAP-positive astrocyte activation, and neuronal loss was examined in cerebellar sections. Ibudilast administration significantly reversed VPA-induced behavioral impairments and attenuated neuroinflammation and oxidative stress. It also reduced astrocytic activation and restored cerebellar neuronal integrity. These findings demonstrate that ibudilast confers neuroprotective and anti-inflammatory effects, effectively ameliorating both behavioral and biochemical deficits associated with ASD.

Ibudilast for the Treatment of Experimentally Induced Colitis via Anti-Inflammatory Modulation

Oubaid E. N., et al. PHARMACIA, 2023, 70, 187-195.

In this study, ibudilast was evaluated for its therapeutic efficacy in acetic acid-induced colitis in Wistar rats, emphasizing its anti-inflammatory activity. Colitis was experimentally induced through intra-rectal administration of 2 mL of 4% acetic acid. Fifty adult rats were randomized into five groups: control, acetic acid alone, acetic acid with vehicle, acetic acid with sulfasalazine (100 mg/kg/day), and acetic acid with ibudilast (30 mg/kg/day). Ibudilast was administered orally for ten consecutive days following colitis induction. The therapeutic effects were assessed by monitoring disease activity index (DAI), macroscopic colon damage scores (MAC), and histopathological evaluations. Ibudilast significantly attenuated colitis severity, as evidenced by reduced DAI and MAC values and improved histological architecture. Furthermore, ibudilast suppressed colonic expression of proinflammatory cytokines, including TNF-α and IL-1β, and markedly decreased myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. These findings underscore the potential of ibudilast as an effective anti-inflammatory agent for experimental colitis, primarily through the down-regulation of cytokine expression and MPO activity.

Ibudilast for the Inhibition of Macrophage Migration Inhibitory Factor (MIF) in Leptospirosis Models

Sumaiya K, et al. Microbial Pathogenesis, 2022, 173(A), 105786.

Ibudilast was experimentally repurposed to target macrophage migration inhibitory factor (MIF) in leptospirosis. Seventeen candidate compounds, including ibudilast, were screened for MIF tautomerase inhibition via dopachrome tautomerase assay. Ibudilast demonstrated potent anti-MIF activity with an IC₅₀ of 9.5 ± 5.6 μM, closely matching that of the standard antagonist ISO-1 (6.2 ± 3.8 μM). In vitro assays using THP-1 monocytes exposed to leptospiral lipopolysaccharide (LPS) revealed that ibudilast significantly suppressed pro-inflammatory mediators such as ICAM, p38 and p44/42 MAPKs, and key cytokines. It also mitigated oxidative stress, preserved mitochondrial membrane potential, and reduced LPS-induced cell death. In vivo, BALB/c mice treated with ibudilast exhibited reduced histopathological damage and inflammatory cytokine levels, with survival rates improving from 25% to 66%. Cytotoxicity, hemocompatibility, and apoptosis assays confirmed ibudilast's safety at concentrations ≤50 μM, showing no significant toxicity or erythrocyte lysis.

Ibudilast for the Prevention of Tacrolimus-Induced Neurotoxicity in Rodent Models

Zhang W, et al. Toxicology and Applied Pharmacology, 2022, 449, 116112.

This study demonstrates the neuroprotective effect of ibudilast in mitigating tacrolimus-induced neurotoxicity, emphasizing its experimental application in both in vitro and in vivo models. Human SH-SY5Y neuroblastoma cells were exposed to tacrolimus to induce cytotoxicity, and ibudilast was applied to assess its protective efficacy, revealing a significant reduction in cell death. For in vivo evaluation, Wistar rats were administered tacrolimus subcutaneously (2.5 or 5.0 mg/kg/day) for 14 days, with ibudilast (7.5 mg/kg/day, intraperitoneally) introduced two days prior to the higher dose of tacrolimus. Neurological damage was assessed via histopathological analyses using Nissl and TUNEL staining. The results showed neuronal apoptosis localized to the cerebral cortex and hippocampal CA1 region, with no damage observed in the CA3, dentate gyrus, or cerebellum. Ibudilast co-administration significantly attenuated these effects without altering tacrolimus pharmacokinetics in brain tissue. Importantly, brain tacrolimus concentrations correlated directly with neurotoxicity severity.

Synthetic Use

Upstream Synthesis Route 1

• 7583-90-6
• 97-72-3

• 50847-11-5
• 59942-84-6

Reference: [1] Patent: WO2007/146087, 2007, A2, . Location in patent: Page/Page column 43

Upstream Synthesis Route 2

• 7583-90-6
• 97-72-3

• 50847-11-5
• 59942-84-6

Reference: [1]Current Patent Assignee: MEDICINOVA INC - WO2007/146087, 2007, A2
Location in patent: Page/Page column 43