bentamapimod (PGL5001) / Gedeon Richter - LARVOL DELTA

Evaluation of C-Jun N-terminal Kinase (JNK) Inhibitors in a Vascularized Microphysiological Model of Endometriosis (WCE 2025) - "C-Jun N-terminal kinase inhibitor (JNKi) bentamapimod has demonstrated lesion regression in vivo but lacks potency required for clinical translation...Conclusion Here we describe our efforts to systematically evaluate the effects of highly selective JNKi in a microphysiological hydrogel platform that recapitulates critical aspects of the endometriosis microenvironment. This microfluidic culture model has potential for impacts on a better scientific understanding of endometriosis and new drug development."

Endometriosis • Gynecology • Women's Health • CD14 • IL1B • IL6 • MAPK8 • MMP9 • TNFA

AS602801 treatment suppresses breast cancer metastasis to the brain by interfering with gap-junction communication by regulating Cx43 expression. (PubMed, Drug Dev Res) - "AS602801 downregulates the expressions of JNK and Cx43 to suppress the gap-junction activity. AS602801 also inhibits the communication between breast cancer cells and astrocytes, thus contributing to the treatment of brain metastasis in breast cancer."

Journal • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • GJA1 • MAPK8

State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials. (PubMed, Gynecol Endocrinol) - "Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors. Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration."

Journal • Review • Endometriosis • Gynecology • Immune Modulation • Inflammation • Musculoskeletal Pain • Pain • Women's Health

Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801. (PubMed, J Neurosurg) - "The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation."

Journal • Preclinical • Brain Cancer • Fibrosis • Genetic Disorders • Neurofibromatosis • Oncology • Otorhinolaryngology • Solid Tumor • MAPK8 • NF2 • POSTN

SIRT7- and JNK-Mediated Akt Supports Glycolysis-Driven Lipogenesis and Proliferation of Human Pulmonary Arterial Vascular Smooth Muscle Cells in Pulmonary Arterial Hypertension (ATS 2022) - "Using immunocytochemical analysis with fluorescent probe BODIPY, cell growth (cell counts) and proliferation (Ki67) assays, we found that accumulation of intracellular lipids and increased proliferation of PAH PAVSMC were preserved in lipid-free conditions but suppressed by non-metabolizable analog of glucose 2-Deoxy-D-glucose and partially restored by addition of pyruvate...shRNA SIRT7 and JNK inhibitor bentamapimod downregulated lipogenic enzymes ACLY and ACC in human PAH PAVSMC... Human PAH PAVSMC have up-regulated lipogenesis supported in Akt- and glycolysis-dependent manner to sustain increased cell growth. Inhibition of Akt-lipogenesis axis reduces proliferation and induces apoptosis of human PAH PAVSMC. In aggregate, our data provide a link between glycolysis, lipogenesis and proliferation of human PAH PAVSMC and call for further studies to determine potential attractiveness of SIRT7/JNK-Akt-lipogenesis axis as a target pathway for therapeutic intervention."

Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • FASN • MAPK8

AS602801 sensitizes glioma cells to temozolomide and vincristine by blocking gap junction communication between glioma cells and astrocytes. (PubMed, J Cell Mol Med) - "AS602801 down-regulated CX43 expression by inhibiting JNK. And AS602801 also sensitized glioma cells to TMZ/VCR by blocking the gap junction communication between glioma cells and astrocytes via down-regulating CX43, indicating its potential role as a novel adjuvant chemotherapeutic agent in the treatment of glioma."

Journal • Glioma • Oncology • Solid Tumor • CASP3 • GJA1

PGL5001 Proof of Concept Study in Inflammatory Endometriosis (clinicaltrials.gov) - P2a; N=24; Completed; Sponsor: PregLem SA; Recruiting -> Completed

Trial completion • Biosimilar • Endometriosis • Immunology • Oncology • Renal Cell Carcinoma

The JNK inhibitor AS602801 Synergizes with Enzalutamide to Kill Prostate Cancer Cells In Vitro and In Vivo and Inhibit Androgen Receptor Expression. (PubMed, Transl Oncol) - "Here, we tested the effects of the MEK inhibitors PD0325901 and GSK1120212, ERK1/2 inhibitor GDC-0994, and the JNK inhibitor AS602801 alone and in combination with the AR inhibitor enzalutamide (ENZ) in androgen-sensitive LNCaP cells and androgen-resistant C4-2 and 22Rv1 cells. Surprisingly, mechanistic studies and Nanostring data suggest that AS602801 likely activates JNK signaling to induce apoptosis. Since AS602801 had sufficient safety and toxicity profile to advance from Phase I to Phase II in clinical trials, repurposing of this compound may represent an opportunity for rapid translation for clinical therapy of CRPC patients."

Journal • AR • MAPK8

"Our latest paper shows AS602801 eliminates Andogen Receptor mRNA expression and prevents prostate tumor growth. @PCF_Science @PCFnews @soulehoward1 @emory_research" (@Carlos_S_Moreno)

Combination therapies to prevent resistance to androgen deprivation therapy in prostate cancer (AUA 2019) - " Cell Viability and Cytotoxicity Assays, MTT assays, Transwell Cell Migration and Invasion assays were used to evaluate the viability, cytotoxicity, proliferation, migration and invasion abilities of LNCaP cell after treated with Enzalutamide and MEK inhibitors PD0325901 and GSK1120212, ERK1/2 inhibitor GDC-0994, and the JNK inhibitor AS602801 alone and in combination with enzalutamide in androgen-sensitive LNCaP and MDA-PCa-2b cells. combination therapy targeting AR and MEK and/or JNK signal pathways may be an effective treatment for recurrent prostate cancer. We are currently investigating the most promising combinations of enzalutamide with JNK inhibitors for anti-tumorigenic effects in vivo using a mouse xenograft model. Source of Funding: These studies were supported in part by the Dunwoody Golf Club Prostate Cancer Research Award, a philanthropic award provided by the Winship Invest$ Prostate Cancer Research Pilot Grant Program."

Combination therapy

AS602801 Sensitizes Ovarian Cancer Stem Cells to Paclitaxel by Down-regulating MDR1. (PubMed, Anticancer Res) - "AS602801 chemosensitized ovarian CSCs to paclitaxel by reducing the expression of MDR1."

Cancer stem cells • Journal

AS602801, an Anticancer Stem Cell Candidate Drug, Reduces Survivin Expression and Sensitizes A2780 Ovarian Cancer Stem Cells to Carboplatin and Paclitaxel. (PubMed, Anticancer Res) - "AS602801, which reduces survivin expression, can chemosensitize ovarian CSCs and is a candidate drug that targets the chemoresistance, tumor-initiating capacity and metastasis of CSCs."

Cancer stem cells • Journal