nanvuranlat (JPH203) / J-Pharma, Ohara Pharma - LARVOL DELTA

Anti-Tumor Potential of Selective L-Type Amino Acid Transporter (LAT1) Inhibitor, JPH203, in Patient-Derived Canine Bladder Cancer Organoids. (PubMed, Int J Mol Sci) - "Furthermore, intraperitoneal administration of JPH203 decreased the growth and tumor weight of BC organoid-derived xenograft in immunodeficient mice with an induction of apoptosis and a decrease in LAT1 expression compared to vehicle-administered mice. Therefore, the present study demonstrates that JPH203 exerts anti-tumor effects in canine BC through modulation of the mTOR signaling pathway and supports further investigation of LAT1-targeted therapy for canine BC."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Clinical and LAT1 Biomarker Correlates of Clinical Benefit from Nanvuranlat (JPH203) in Advanced Biliary Tract Cancer: A Post Hoc Analysis. (PubMed, Cancers (Basel)) - " Nanvuranlat was associated with a lower hazard of progression or death than placebo, whereas the OS estimate was less conclusive. The subgroup and exposure findings remain exploratory but support prospective evaluation of resection status, anatomical subtype, and LAT1 expression."

Biomarker • Journal • Retrospective data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

A Redox-Responsive Nanoplatform Modulating the Treg/Th17 Balance Through LAT1- and PPARγ-Related Pathways for Psoriasis Therapy. (PubMed, Small) - "Here, we developed a redox-responsive nanoparticle-based topical hydrogel, PB-MJ@N/G, that co-delivers morin (a natural PPARγ activator that promotes Treg proliferation) and JPH203 (a LAT1 inhibitor that suppresses Th17 cell expansion) to modulate the Treg/Th17 balance in psoriatic skin...In both in vitro and in vivo models, PB-MJ@N significantly restored the Treg/Th17 ratio, alleviated psoriatic inflammation, and attenuated relapse-associated lesion development in a recurrence model. This topical, stimuli-responsive nanoparticle presents a powerful immunotherapeutic strategy for psoriasis, supporting sustained treatment-associated benefit."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • PPARG

SLC7A5 promotes colorectal cancer liver metastasis by reprogramming tryptophan metabolism through the Kyn/XANA‒AhR axis and reshaping the immune microenvironment. (PubMed, Clin Transl Med) - "Collectively, our findings reveal that SLC7A5 drives CRLM through tryptophan/Kyn/XANA-AhR signalling and concomitant remodelling of the TIME, positioning SLC7A5 as a promising target for combination therapy with anti-PD-1 in CRLM."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • SLC7A5

SLC7A5 promotes vascular remodeling in the rat carotid artery following balloon injury through PI3K/Akt signaling pathway. (PubMed, Front Pharmacol) - "Pharmacological inhibition of SLC7A5 using JPH203 produced similar effects in vitro and reduced neointimal hyperplasia and improved vascular function in vivo, with suppression of PI3K/Akt signaling...SLC7A5 promotes proliferative and migratory responses, at least in part through activation of the PI3K/Akt signaling pathway. Targeting SLC7A5 may represent a potential therapeutic strategy for vascular remodeling-associated cardiovascular diseases."

Journal • Preclinical • Cardiovascular • MMP2 • PCNA • SLC7A5

Human blood-brain barrier spheroid models for the evaluation of drugs targeting brain vascular inflammation. (PubMed, J Pharmacol Sci) - "Then, we tested whether natalizumab (a monoclonal antibody used for multiple sclerosis treatment) and JPH203 (an inhibitor of L-type amino acid transporter 1) could modulate the immune cell adhesion. Both agents remarkably suppressed the cytokine-induced THP-1 cell adhesion to 0.2-fold relative to the respective controls. To summarize, our results demonstrate that the hiMCS-BBB models exhibit key features of BBB inflammation in response to inflammation stimuli and recapitulate clinically relevant responses to anti-inflammatory drugs, highlighting their potential to accelerate BBB-targeting drug development."

Journal • Preclinical • CNS Disorders • Inflammation • Multiple Sclerosis • CLDN5 • IFNG • SELP • TNFA

Decoding the immunometabolic landscape identifies SLC7A5 as a vulnerability in chemo-immunotherapy resistant TNBC. (PubMed, Clin Exp Med) - "Crucially, pharmacological blockade of SLC7A5 with the specific inhibitor JPH203 abrogates this metabolic toxicity, restores T cell effector function, and enhances the anti-tumor efficacy of combined cisplatin and anti-PD-1 therapy. Collectively, our findings delineate the Kynurenine-SLC7A5 metabolic axis as a critical driver of immunosuppression, providing a compelling rationale for integrating amino acid transport blockade to overcome resistance to chemo-immunotherapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL9 • IDO1 • SLC7A5

RBM12 Maintains Glioma Stem Cells by Activating Amino Acid-Dependent mTORC1 Signaling via SLC7A5 mRNA Stabilization. (PubMed, Adv Sci (Weinh)) - "Importantly, pharmacological inhibition of the RBM12-SLC7A5 axis using the SLC7A5 inhibitor JPH203 effectively suppresses GBM growth. These findings elucidate a novel role for RBM12-SLC7A5 signaling in the malignant growth of GBM and highlight the therapeutic potential of targeting this axis for GBM treatment."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ALKBH5 • SLC7A5

J Pharma…and Uniphar…jointly announced progress in the development of JPH203 (nanvuranlat), a novel LAT1 inhibitor for the treatment of second-line biliary tract cancer (J Pharma Press Release) - "Following alignment with the U.S. Food and Drug Administration (FDA), the program has advanced into Phase 3 clinical development and initial patients are now enrolled in the global study....J Pharma has initiated its global Phase 3 study, with the first patients now successfully randomized....Uniphar Development continues to serve as J Pharma’s U.S. regulatory and development partner, providing ongoing strategic support as the Phase 3 trial progresses."

Trial status • Biliary Tract Cancer

Preclinical Evaluation of 5F-αMe-3BPA for Improving Pharmacokinetics in Boron Neutron Capture Therapy. (PubMed, Pharmaceutics) - "Time-dependent cellular uptake and intracellular retention of BPA and 5F-αMe-3BPA were evaluated in T3M-4 pancreatic cancer cells with or without the LAT1 inhibitor JPH203. Probenecid pretreatment increased plasma exposure, reduced early renal accumulation, and significantly enhanced tumor boron accumulation, reaching approximately twofold higher levels than control. These findings establish 5F-αMe-3BPA as a highly LAT1-selective BNCT candidate and identify probenecid pretreatment as a clinically translatable pharmacokinetic strategy for maximizing therapeutic boron delivery."

Journal • PK/PD data • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor

ADPB Sensitivity in Breast Cancer is Correlated with LAT1 Expression: An in vitro Study of a Novel Theranostic Candidate. (PubMed, Breast Cancer (Dove Med Press)) - "Few ligand such as JPH203 (KYT-0353), a known tyrosine analogue that specifically blocks LAT1, but have limitation...Study found an inverse relationship between LAT1 expression and IC5 0 in all cell lines, with higher LAT1 levels correlated with lower IC5 0. In this exploratory in vitro study, ADPB predominantly induces cytostatic effects, with cellular sensitivity associated with LAT1 expression in breast cancer cell line."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

KRAS inhibition-induced GSDME-mediated pyroptosis and its augmentation by LAT1 inhibition in KRAS-mutant lung cancer (AACR 2026) - "LAT1 involvement was assessed using the LAT1 inhibitor JPH203 and rescue with spermidine. Mutation-specific KRASi induced pyroptosis in KRAS G12C and G12D mutant NSCLC cell lines, as evidenced by LDH release, characteristic pyroptotic morphology, and GSDM cleavage... We identify GSDME-mediated pyroptosis as a previously unrecognized mechanism of KRASi-induced cell death in KRAS-mutant NSCLC. KRASi promotes both the generation and stabilization of GSDME-NT, while LAT1 inhibition amplifies this process by increasing metabolic stress and reducing GSDME-NT degradation. These findings support metabolic modulation, specifically LAT1 inhibition, as a promising combination strategy to enhance KRAS-targeted therapy and potentially improve immunogenic tumor cell death in KRAS-mutant NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CASP3 • CASP9 • GSDME • KRAS • MYC

Beacon-BTC: A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (clinicaltrials.gov) - P3 | N=480 | Recruiting | Sponsor: J-Pharma Co., Ltd. | Initiation date: Jan 2026 ➔ Apr 2026

Trial initiation date • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR2 • HER-2 • IDH1 • MSI • NTRK • PD-L1

In situ delivery of JPH203 via camptothecin-peptide conjugate nanoassemblies to trigger ferroptosis in triple-negative breast cancer. (PubMed, J Control Release) - "Importantly, CPCs-JPH promotes dendritic cell maturation, activates CD8+ T-cell responses, and significantly improves survival outcomes in orthotopic 4 T1 tumor-bearing mice. This work establishes a multifunctional and enzyme-responsive nanoplatform that harnesses ferroptosis to overcome therapeutic resistance while concurrently engaging innate and adaptive immunity in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • SLC7A5

Comparative cytotoxicity of novel mercury species α-mercuri-acetaldehyde and α-mercuri-acetic acid versus methylmercury in SH-SY5Y cells. (PubMed, J Toxicol Sci) - "The roles of L-type amino acid transporter 1 (LAT1) and multidrug resistance-associated proteins (MRPs) were evaluated using the inhibitors JPH203 (1 µM) and MK571 (10 µM), respectively...HgCH2CHO and HgCH2COOH were approximately 2-5-fold less cytotoxic than MeHg and exhibited substantially lower intracellular mercury levels. Our findings suggest that HgCH2CHO and HgCH2COOH are unlikely to have neurotoxic potential comparable to that of MeHg."

Clinical • Journal • Neuroblastoma • Oncology • Solid Tumor

Beacon-BTC: A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (clinicaltrials.gov) - P3 | N=480 | Recruiting | Sponsor: J-Pharma Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR2 • HER-2 • IDH1 • MSI • NTRK • PD-L1

Glioma cells achieve malignant progression by fusion with macrophages to gain high SLC7A5 expression. (PubMed, J Neurooncol) - No abstract available

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • SLC7A5

Intrinsic resistance to RAS inhibitors is driven by dysregulation of KRAS degradation. (PubMed, Nat Commun) - "Co-inhibition of mTOR or the SLC3A2/SLC7A5 complex using dactolisib or JPH203 restores sensitivity to KRAS inhibitors in vitro and in vivo. These findings support combinatorial targeting of mTOR signaling or amino acid transport to overcome intrinsic resistance in KRAS-mutant lung cancer."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HIF1A • KRAS • LZTR1 • SLC3A2 • SLC7A5

Beacon-BTC: A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer (clinicaltrials.gov) - P3 | N=480 | Not yet recruiting | Sponsor: J-Pharma Co., Ltd.

New P3 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Can the tumor microenvironment attenuate drug efficacy? Potential vulnerabilities of LAT1 inhibitors. (SNO 2025) - "The antitumor effects of nanvuranlat and JPH034 on glioma cells in vitro, are influenced by concentrations of essential amino acids and albumin. Specifically, amino acids decreased impact of the competitive inhibitor (nanvuranlat) while albumin decreased impact of the non-competitive inhibitor (JPH034). These results suggest that the composition of the tumor microenvironment, which is impacted by BBB-disruption within GBM may differentially attenuate the therapeutic efficacy of certain drugs including LAT1 inhibitors."

Biomarker • Clinical • Tumor microenvironment • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Sustained reductions in valine and isoleucine mediate anti-cancer pharmacological effects of inhibiting amino acid transporter LAT1 in cancer cells. (PubMed, Cancer Metab) - "Reductions in valine and isoleucine in cancer cells primarily account for the multifaceted anti-cancer pharmacological activities of LAT1 inhibition by nanvuranlat. This study establishes the molecular basis for LAT1-targeted therapy and highlights growth-promoting processes in cancer cells that can be exploited pharmacologically by modulating the availability of specific amino acids."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • SLC7A5

Targeting Amino Acid Transporter in Malignant Peripheral Nerve Sheath Tumors: A Strategy to Enhance Efficacy of Chemotherapy and Targeted Therapy (SNO 2025) - "JPH203 induced dose-dependent growth inhibition in multiple MPNST cell lines (IC₅₀: 10-30 µM) and reduced phosphorylated p70S6 levels in a dose- and time-dependent manner, indicating mTORC1 pathway suppression. Combination treatment with LAT1 inhibitor and doxorubicin enhanced cytotoxicity compared to monotherapy... These findings support LAT1 inhibition as a promising therapeutic strategy in MPNST. Synergy with chemotherapy and targeted agents such as MEK inhibitors highlights the potential to exploit metabolic vulnerabilities and enhance the efficacy of existing treatment regimens in this challenging sarcoma subtype."

Clinical • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SLC7A5

Targeting Amino Acid Transporter in Malignant Peripheral Nerve Sheath Tumors: A Strategy to Enhance Efficacy of Chemotherapy and Targeted Therapy (WFNOS 2025) - "JPH203 induced dose-dependent growth inhibition in multiple MPNST cell lines (IC₅₀: 10-30 µM) and reduced phosphorylated p70S6 levels in a dose- and time-dependent manner, indicating mTORC1 pathway suppression. Combination treatment with LAT1 inhibitor and doxorubicin enhanced cytotoxicity compared to monotherapy... These findings support LAT1 inhibition as a promising therapeutic strategy in MPNST. Synergy with chemotherapy and targeted agents such as MEK inhibitors highlights the potential to exploit metabolic vulnerabilities and enhance the efficacy of existing treatment regimens in this challenging sarcoma subtype."

Clinical • Brain Cancer • Neurofibrosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SLC7A5

Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes. (PubMed, Sci Rep) - "ATP-competitive mTOR inhibitor AZD8055 (1 μM) suppressed JPH203-induced protein synthesis. JPH203 treatment increased intracellular glutamine concentration. These results suggest that inhibition of LAT1 function augments muscle protein synthesis, possibly through the activation of rapamycin-insensitive mTOR signaling; elevated intracellular glutamine levels may contribute to the enhancement of muscle protein synthesis induced by LAT1 inhibition."

Journal • EIF4EBP1

Can the tumor microenvironment attenuate drug efficacy? Potential vulnerabilities of LAT1 inhibitors. (WFNOS 2025) - "The antitumor effects of nanvuranlat and JPH034 on glioma cells in vitro, are influenced by concentrations of essential amino acids and albumin. Specifically, amino acids decreased impact of the competitive inhibitor (nanvuranlat) while albumin decreased impact of the non-competitive inhibitor (JPH034). These results suggest that the composition of the tumor microenvironment, which is impacted by BBB-disruption within GBM may differentially attenuate the therapeutic efficacy of certain drugs including LAT1 inhibitors."

Biomarker • Clinical • Tumor microenvironment • Brain Cancer • Glioblastoma • Solid Tumor