An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain PDE4 Engagement, Pharmacokinetics and Safety of Single Oral Doses of GSK356278, Using 11C-(R)-Rolipram as a PET Ligand(s)

This study will investigate if a new experimental drug to treat Huntington's Disease gets into the brain. If it does get into the brain the study will explore the relationship between the amount of drug in the brain and the amount of drug in the blood. The study will involve healthy male volunteers.

Start Date22 Nov 2011

Sponsor / Collaborator

GSK Plc

NCT00369798

/ CompletedPhase 1IIT

Antidepressant Effects on cAMP Specific Phosphodiesterase (PDE 4) in Depressed Patients

The primary purpose of this protocol is to compare PDE4 levels before and after starting a selective serotonin reuptake inhibitor (SSRI) sertraline, citalopram or escitalopram in unmedicated depressed patients. The secondary purpose is to compare PDE4 levels between unmedicated depressed patients and healthy subjects.

Start Date02 Aug 2006

Sponsor / Collaborator

National Institute of Mental Health

NCT00011375

/ CompletedPhase 2IIT

Safety, Tolerability & Effects of Rolipram on Inflammatory Activity in the Central Nervous System in Multiple Sclerosis. A Phase II, Open Label Crossover Trial Using MRI as an Outcome Measure

This study will evaluate the safety, tolerability, and effect of the drug Rolipram on multiple sclerosis (MS). It will examine whether Rolipram can dampen the part of the immune response believed to lead to MS and reduce disease activity.
Patient with multiple sclerosis who are between the ages of 18 and 65 may be eligible for this study. Candidates will be screened with a complete neurological and medical evaluation. Participants will complete three study phases-baseline, treatment and follow-up, as follows:
Baseline (3 months) - Approximately four magnetic resonance imaging (MRI) scans will be obtained to assess MS activity. Participants with MS activity above a certain level will continue with the treatment phase.
Treatment (8 months) - Patients will take Rolipram tablets in increasing doses every 2 to 3 days for the first month of this phase until their individual maximum tolerated dose is established. Dosing will continue at that level for the rest of the treatment phase. Dosing is in the morning, midday and evening. Patients will be seen monthly in the clinic for examination and MRI scans.
Follow-up - Participants will have monthly exams and MRIs for 3 months following the treatment phase, after which their participation in the study ends.
Patients' monthly visits during treatment and follow-up include a neurological examination to assess disease status; MRI to assess brain changes; and blood and urine collection to monitor liver, kidney and other functions. In addition, a lumbar puncture (spinal tap) is done during the last month of the baseline phase and one month after treatment ends to study changes in the spinal fluid surrounding the brain and spinal cord, and leukapheresis is done once during the last month of the baseline phase and once during the last month of treatment to collect white blood cells for study. These procedures involve the following:
MRI uses a strong magnetic field and radio waves instead of X-rays to produce images showing structural and chemical changes in tissues. The patient lies on a table in a narrow cylinder (the scanner) containing a magnetic field and images are taken. A contrast agent called gadolinium is injected into a vein during the last set of images to help identify new lesions. Magnetic resonance spectroscopy, which is similar to MRI, is also done once during the baseline phase, at 4 months and at 8 months to measure brain chemicals. For the spinal tap, a local anesthetic is given and a needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. For leukapheresis, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm.
Patients may also have studies to measure levels of Rolipram in the blood. These are done on study days 1 and 29 and at months 2, 4, and 6. For days 1 and 29, a catheter is placed in an arm vein and 4 ml. of blood is drawn immediately before the morning dose and at several intervals from 20 minutes to 6 hours after the dose. For the other tests, a single 4-ml sample is collected before the noon dose.

Start Date01 Feb 2001

Sponsor / Collaborator

National Institute of Neurological Disorders & Stroke

100 Clinical Results associated with Rolipram

100 Translational Medicine associated with Rolipram

100 Patents (Medical) associated with Rolipram

2,814

Literatures (Medical) associated with Rolipram

01 Jun 2025·BIOMATERIALS

Regulating astrocyte phenotype by Lcn2 inhibition toward ischemic stroke therapy

Article

Author: Yang, Mengyi ; Zhang, Aohan ; Pan, Jingmei ; Guo, Xing ; Liu, Hua ; Zhou, Shaobing ; Xiao, Renmin

Astrocytes can be reacted to "reactive astrocytes" after ischemia-reperfusion injury, in which A1 phenotype causes neuronal and oligodendrocyte death, whereas the A2 phenotype exerts neuroprotective effects, thus regulating reactive astrocyte to A2 type is a potential target for stroke therapy. Lcn2 level is highly associated with the phenotypic polarization of astrocytes. We found that silencing the Lcn2 gene by adeno-associated virus (AAV)-Lcn2 shRNA adenovirus resulted in a dramatic decrease in A1-type astrocytes and increase in A2 astrocytes in MCAO mice. Hence, a nanoplatform was developed for stroke therapy by inhibiting Lcn2. This system was fabricated by N-acetyl Pro-Gly-Pro peptide-decorated rod-shaped poly (lactic-co-glycolic acid) nanoparticles loading with rolipram (AP@R). The nanodrug can be efficiently taken up by neutrophils simultaneously through morphology-mediated passive targeting and Cxcr2 receptor-mediated active targeting, subsequently crossing the blood-brain barrier (BBB) by hitchhiking neutrophils. When accumulating at the brain parenchyma, the released rolipram can inhibit the Lcn2 level, thereby reversing the astrocyte phenotype to alleviate neuroinflammation and promote BBB repair. This work provides a new strategy for treating ischemic stroke.

14 Apr 2025·CHEMPHYSCHEM

Discriminating High from Low Energy Conformers of Druglike Molecules: An Assessment of Machine Learning Potentials and Quantum Chemical Methods

Article

Author: Bryce, Richard A. ; Kong, Linghan

Abstract:

Accurate and efficient prediction of high energy ligand conformations is important in structure‐based drug discovery for the exclusion of unrealistic structures in docking‐based virtual screening and de novo design approaches. In this work, we constructed a database of 140 solution conformers from 20 druglike molecules of varying size and chemical complexity, with energetics evaluated at the DLPNO‐CCSD(T)/complete basis set (CBS) level. We then assessed a selection of machine learning potentials and semiempirical quantum mechanical models for their ability to predict conformational energetics. The GFN2‐xTB tight binding density functional method correlates with reference conformer energies, yielding a Kendall's τ of 0.63 and mean absolute error of 2.2 kcal/mol. As putative internal energy filters for screening, we find that the GFN2‐xTB, ANI‐2x and MACE‐OFF23(L) models perform well in identifying low energy conformer geometries, with sensitivities of 95 %, 89 % and 95 % respectively, but display a reduced ability to exclude high energy conformers, with respective specificities of 80 %, 61 % and 63 %. The GFN2‐xTB method therefore exhibited the best overall performance and appears currently the most suitable of the three methods to act as an internal energy filter for integration into drug discovery workflows. Enrichment of high energy conformers in the training of machine learning potentials could improve their performance as conformational filters.

01 Apr 2025·BIOORGANIC CHEMISTRY

Hydroxychavicol derivatives from Piper betle Linn. as natural PDE4 inhibitors with anti-inflammatory effects

Article

Author: Luo, Hai-Bin ; Ou, Jiazhi ; Cheng, Zhongbin ; Zhou, Qian ; Huang, Yiyou ; Qiu, Haihang ; Li, Junyi ; Xie, Shenghong ; Wang, Chunying ; Huang, Peiluo ; Wu, Peng ; Zhong, Fang ; Zhang, Yan

PDE4 inhibitors have been developed as anti-inflammatory medications primarily used in the clinical treatment of pulmonary inflammations such as asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. However, the application of these drugs is usually restricted by obvious side effects, such as nausea and vomiting. Our previous study found that several natural PDE4 inhibitors or their modified derivatives showed minimal side effects, particularly reduced incidence of nausea and vomiting, which aroused our interest in searching for natural PDE4 inhibitors. In this study, a chemical investigation of an active fraction of Piper betle L. leaves led to the characterization of 23 hydroxychavicol derivatives, including 18 hydroxychavicol-type lignans. Compounds 1-9 were new lignans, with three of them being racemates that were eventually resolved into isolated (+)- and (-)-enantiomers. Compounds 1-5 and 10, neolignans characterized by a dioxane moiety, were unique to this species within the genus Piper. Compounds 5 and 10 were the sole sesquineolignans found in the genus Piper. Compounds 5, 7-14, 16, 17, and 21 exhibited considerable inhibition towards PDE4 with IC₅₀ values ranging from 1.8 to 10 μM, with hit 7 exhibiting remarkable activity (1.8 μM). Further anti-inflammatory assays revealed that compounds 5, 7, 9, and 16 decreased the expression of several key inflammatory mediators in LPS-stimulated RAW 264.7 cells. Notably, 16 was comparable to the positive control rolipram at the same concentration of 10 μM. A primary study of the mechanism of action revealed that 16 may exert anti-inflammatory effect by inhibiting the NF-κB signaling pathway, displaying significant inhibition of the phosphorylation of IκB-α and p65 at concentrations of 5 and 10 μM. These findings suggest that hydroxychavicol derivatives from P. betle L. leaves may serve as new PDE4 inhibitors, offering promising leads for the development of anti-inflammatory medications.

News (Medical) associated with Rolipram

30 Jul 2024

·www.businesswire.com

New Study Describes a Functional, Aged, Human Cell-Based Platform That Examines the Contribution of Senescence in Alzheimer’s Disease Progression, and Response to Therapeutics

ORLANDO, Fla.--( BUSINESS WIRE )--Researchers from Hesperos and the University of Central Florida have developed a groundbreaking model using human induced pluripotent stem cell (iPSC)-derived cortical neurons to better understand and combat Alzheimer’s disease (AD). Their study, “ A functional aged human iPSC-cortical neuron model recapitulates Alzheimer’s disease, senescence, and the response to therapeutics ," has been published in the prestigious journal Alzheimer's & Dementia ® : The Journal of the Alzheimer's Association. doi.org/10.1002/alz.14044 AD affects an estimated 6.2 million Americans aged 65 and older, with projections suggesting this number could reach 14 million by 2050. Current treatments, such as acetylcholinesterase inhibitors and NMDA receptor antagonists, provide only temporary relief. The high failure rate of AD clinical trials highlights the need for a better understanding of the pathophysiology and drug mechanisms. The study addresses a critical challenge in Alzheimer’s research: the degeneration of cortical layers associated with cognitive decline. Despite substantial efforts to date, few current AD therapies are not disease-modifying. The team accurately reproduced key biological aspects of aging and senescence in a multi-cellular microphysiological system (MPS), also known as a Human-on-a-Chip. This new approach reveals how cellular aging, also known as senescence, contributes to disease progression and therapy resistance, providing researchers with an accurate, human platform to further understand the disease and potential therapeutics in a living context. Further, since other platforms at Hesperos, based on neurodegenerative diseases, have been accepted by the Food and Drug Administration (FDA) for efficacy data, it provides a new method to accelerate development and regulatory submissions of new treatments. This model provides an invaluable tool for real-time measurement of neuronal activity and aging biomarkers, facilitating drug screening and the development of AD therapies. It also reveals complex disease mechanisms, such as the role of inflammatory factors in neuronal senescence and how it differs from non-disease age-related controls, offering new targets for intervention. Researchers cultured human iPSC-derived cortical neurons on patterned microelectrode arrays to measure long-term potentiation (LTP) noninvasively. LTP, a quantifiable metric for learning and memory, is directly impacted by central nervous system neurodegeneration. By treating these neurons with pathogenic amyloid-β (Aβ), a peptide that plays a central role in development of AD, to mimic disease pathophysiology, the team was able to analyze senescence and therapeutic responses. The study demonstrates that this novel human iPSC-cortical neuron model of aging, cultured in serum-free, defined conditions, accurately recapitulates hallmarks of AD showing the following: Pathological Insights : Aβ42 induced synaptic damage, accelerated neuronal senescence, impaired mitochondrial potential, and increased reactive oxygen species (ROS), leading to oxidative stress and inflammation. Therapeutic Responses : Drugs such as memantine, rolipram, saracatinib, and donepezil improved neuronal function and viability, though they did not completely halt Aβ42-driven senescence. The study underscores the potential of biomimetic MPS systems in translational research. By integrating clinically relevant neuronal function with proteome responses, this platform is poised to accelerate the discovery of novel neuroprotective compounds for AD and other neurological disorders. “This marks a significant step forward in Alzheimer's research by providing a deeper understanding of AD pathophysiology in a human aged MPS platform. We are excited about the potential of this model to transform drug discovery in AD, providing hope for patients,” said J. Hickman, PhD, co-founder and Chief Scientist of Hesperos and Professor of Chemistry at UCF. This research was supported by grants from the National Institutes of Health (R44TR001326, R44AG058330). Research Article : doi.org/10.1002/alz.14044 Nanoscience Technology Center (NSTC) at the University of Central Florida (UCF) The mission of the NSTC is to establish a cutting-edge research program in materials and nanotechnology, provide high quality training for students and facilitate the advance of innovations to solve real world technology challenges. https://nanoscience.ucf.edu/ Hesperos, Inc. Hesperos is a global contract research organization (CRO) providing drug development services using its Human-on-a-Chip ® platform - the most advanced, multi-organ microphysiological systems available today. https://hesperosinc.com

12 Mar 2024

·www.biospace.com

MediciNova Announces New Data and Results of MN-166 (ibudilast) in Chlorine Gas-induced Acute Lung Injury Presented at the 63rd Annual Meeting of the Society of Toxicology

LA JOLLA, Calif., March 12, 2024 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that MediciNova’s collaborator, Perenlei Enkhbaatar, MD, PhD, FAHA, Professor, Department of Anesthesiology, Director, Translational Intensive Care Unit, Charles Robert Allen Professor in Anesthesiology, University of Texas Medical Branch, presented new data and results of a nonclinical study evaluating MN-166 (ibudilast) in a chlorine gas-induced acute lung injury (CIALI) model at the Society of Toxicology (SOT) 63rd Annual Meeting and ToxExpo in Salt Lake City, Utah. The primary objective of this nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) following ALI induced by chlorine (Cl2) gas inhalation in a clinically relevant translational ovine model. In this study, single-dose and multi-dose treatments were evaluated. The primary endpoint was the mean change in the pulmonary function measure PaO2/FiO2, which is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. Additional endpoints included survival, lung mechanics, lung injury, and edema formation evaluated by chest x-ray. The highlights of the presentation, entitled “Evaluation of safety and pharmacological activity of MN-166 (ibudilast) in a clinically relevant ovine model of chlorine-induced acute lung injury” (Abstract # 4296), are as follows: After a Cl2 gas challenge (210 ppm x 30 min) to induce moderate ALI (mean PaO2/FiO2<200 mmHg), the test subjects were randomly assigned to 4 treatment groups: MN-166 (ibudilast) low dose (10 mg) or high dose (20 mg), a positive control (rolipram 1 mg), and vehicle (negative control). Cl2 gas concentration of 210 ppm x 30 min was expected to result in a 20 - 30% mortality rate (Fukuda 2015). Treatment regimens: Single-dose treatment (n=5/group) in which a 30-min IV infusion was given once only, initiated 30 min after completion of the Cl2 challenge Multi-dose treatment (n=3/group) in which 30-min IV infusions were given a total of 4 times, initiated 30 min after the completion of Cl2 gas challenge, then every 12 hours Efficacy Result Single-dose treatment MN-166 (ibudilast) 20 mg and rolipram treatment resulted in greater improvement in mean PaO2/FiO2 and peak airway pressure but dissipated after Hour 12 Multi-dose treatment MN-166 (ibudilast) 20 mg showed greater improvement in mean PaO2/FiO2 ratio (p=0.0001), with animals recovering enough to no longer meet the criteria of ARDS (Berlin ARDS definition 2012) MN-166 (ibudilast) 20 mg also showed greater improvement in peak airway pressure (p<0.05), plateau airway pressure (p<0.05), pulmonary artery pressure (p<0.05), and lung injury score (p<0.05) compared to the other treatment groups MN-166 (ibudilast) 20 mg also maintained cardiac and kidney function compared to the other treatment groups Notably, significance was observed beyond the T=12-hour timepoint, further reinforcing the observed benefit of MN-166 (ibudilast) 20 mg with the multi-dose treatment regimen Survival MN-166 (ibudilast) 20 mg treatment demonstrated a greater survival benefit than the other treatment groups. All animals in the MN-166 (ibudilast) 20 mg group (8 out of 8) survived the 48-hour monitoring period, while 25% (2 out of 8 / arm) animals were euthanized early in other groups upon reaching the euthanasia criteria. Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "We are very pleased to report the positive results in which MN-166 demonstrated a large and significant improvement in pulmonary function and recovery, i.e., no longer having ARDS, attenuation of lung injury, and a higher survival rate in the ovine CIALI model study. Collectively, positive findings from this clinically relevant ovine model, the previously reported lipopolysaccharide (LPS)-induced ARDS nonclinical model, and significant positive results from a clinical trial in hospitalized COVID-19 patients at risk of developing ARDS, we believe MN-166 (ibudilast) shows promise as a candidate for ALI.” This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50121C00022. About MN-166 (ibudilast) MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS). About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety pro MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in Long COVID and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2023 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: Geoff O'Brien Vice President MediciNova, Inc. info@medicinova.com

Phase 2Clinical Result

27 Sep 2023

·www.globenewswire.com

MediciNova Announces Results of Studies under BARDA Contract to Develop MN 166 (ibudilast) as a Medical Countermeasure Against Chlorine Gas-induced Lung Injury

LA JOLLA, Calif., Sept. 27, 2023 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced the results of the nonclinical studies conducted under its contract with the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services, to repurpose MN-166 (ibudilast) as a potential medical countermeasure (MCM) against chlorine gas-induced lung damage such as acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Two different nonclinical models were used to investigate the potential clinical utility of MN-166 (ibudilast) for the treatment of chlorine-induced lung damage. The primary objective of the first nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) following ALI induced by chlorine (Cl2) gas inhalation. In this study, single-dose and multi-dose treatments were evaluated. The primary endpoint was the pulmonary function measure PaO2/FiO2, which is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. After a Cl2 gas challenge to induce moderate ALI (mean PaO2/FiO2<200), the test subjects were divided into four different treatment groups - two different doses of MN-166 (ibudilast) (low dose and high dose), a positive control (rolipram), and a negative control (test article vehicle) - which were infused intravenously (IV) over 30 minutes. In the pilot design single-dose treatment regimen, the test subjects were treated only once after the Cl2 gas challenge was completed. MN-166 (ibudilast) high dose and the positive control were more efficacious than MN-166 (ibudilast) low dose and the negative control until 12 hours after Cl2 exposure but this did not yield statistically significant results for overall pulmonary function. MN-166 (ibudilast) was well tolerated and no safety concerns were observed in the single-dose study. A pharmacokinetic (PK) study was conducted to determine the optimal dosing frequency of MN-166 (ibudilast) in the multi-dose study. In the multi-dose study, based on the PK profile in test subjects, each treatment was given every 12 hours with a total of 4 doses after the Cl2 gas challenge. Treatment with MN-166 (ibudilast) high dose resulted in greater improvement (p=0.0001) in the mean PaO2/FiO2 ratio than MN-166 (ibudilast) low dose, rolipram, and negative control. The mean PaO2/FiO2 ratio decreased (worsened) by 57% from 518.7 mmHg at baseline (the end of the chlorine gas exposure) to 224.8 mmHg at hour 48 in the negative control group. The mean PaO2/FiO2 ratio decreased (worsened) by 36% from 516.0 mmHg at baseline to 327.8 mmHg at hour 48 in the MN-166 (ibudilast) high dose group. At hour 48, the last time point measured in the study, the mean PaO2/FiO2 ratio was 46% higher (better) in the MN-166 (ibudilast) high dose group than in the negative control group (327.8 vs. 224.8 mmHg). Since ARDS is defined as a PaO2/FiO2 ratio less than 300 mmHg, the mean PaO2/FiO2 ratio values indicate that the negative control group was still categorized as having mild ARDS at the end of the 48-hour evaluation period but the MN-166 (ibudilast) high dose group had recovered enough to no longer be defined as having ARDS. MN-166 (ibudilast) was well tolerated and no safety concerns were observed in the multi-dose study. A preliminary proof-of-concept (POC) study was conducted to determine the feasibility of the second nonclinical model as a tool to evaluate MN-166 (ibudilast) as a MCM for chlorine gas exposure. After multiple attempts by MediciNova’s subcontractor to establish the feasibility of the second Cl2-gas induced lung injury model, it was not deemed to be a feasible model to evaluate a drug candidate and there are no evaluable efficacy results from the second nonclinical model POC study. Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "We are very pleased to report the positive results from the multi-dose nonclinical model study in which MN-166 demonstrated a large and significant improvement in pulmonary function and a higher survival rate. We previously reported that MN-166 attenuated histological changes observed in an LPS-induced ARDS nonclinical model, including pulmonary edema in lung tissue, and protected against pulmonary injury by reducing cellular apoptosis in lung tissue. We also previously reported positive and significant outcomes from a clinical trial of MN-166 in hospitalized severe COVID-19 patients at risk of developing ARDS. Combining the positive nonclinical chlorine gas-induced ALI model study results with the positive results from the human clinical trial in severe COVID-19 patients at risk of developing ARDS, we believe MN-166 has potential to treat acute lung disease from various causes. We plan to meet with the FDA to discuss the next steps in this development program. Development of medical countermeasures does not require human clinical trials to establish efficacy when these trials would not be ethical or feasible. There is a great unmet medical need for treatments for chlorine gas exposure as there is no drug approved specifically for this indication. We thank BARDA for their support of this program.” This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50121C00022. About MN-166 (ibudilast) MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS). About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in glioblastoma, Long COVID, and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2022 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: Geoff O'BrienVice PresidentMediciNova, Inc.info@medicinova.com

Clinical ResultPhase 2Phase 3

100 Deals associated with Rolipram

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KEGG	Wiki	ATC	Drug Bank
D01783	Rolipram	-	DB01954

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 3	-	National Institute of Mental Health	-
Multiple Sclerosis	Phase 2	United States	National Institute of Neurological Disorders & Stroke	01 Feb 2001

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SFN2008	Not Applicable	Peripheral Nerve Injuries	-	Rolipram	wdowifhnjs(ktbaklefda) = crzbmcyxec jdecqgpges (hcfavpjhay, 152) View more	-	19 Nov 2008
				Saline	wdowifhnjs(ktbaklefda) = nfbmxzhcnu jdecqgpges (hcfavpjhay, 52)

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Clinical Trial

Identify the latest clinical trials across global registries.

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Approval

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Regulation

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Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis