Delving into the Latest Updates on Nanvuranlat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [2]

Target

SLC7A5

Action

inhibitors

Mechanism

SLC7A5 inhibitors(L-type amino acid transporter 1 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersUrogenital Diseases+ [1]

Active Indication

Biliary Tract NeoplasmsColorectal CancerRenal Cell Carcinoma+ [1]

Inactive Indication-

Originator Organization

J-Pharma Co., Ltd.

Active Organization

J-Pharma Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC23H19Cl2N3O4

InChIKeyXNRZJPQTMQZBCE-SFHVURJKSA-N

CAS Registry1037592-40-7

AbstractThe incidence of hepatocellular carcinoma (HCC) is increasing worldwide annually. However, traditional treatments like surgery, targeted therapy, and immunotherapy have limited efficacy, often accompanied by adverse reactions or drug resistance. Precision therapy via tumor‐specific gene therapy and targeted delivery would potentially improve therapeutic efficiency with desirable biosafety. In this study, CHRDL‐1 is identified in clinic specimens and comprehensively evaluated as a tumor suppressor gene against HCC via activation of the Hippo pathway. By integrating pDNA‐CHRDL‐1, layered double hydroxides, membrane‐penetrating peptide and folic acid, a novel nano‐platform (FT‐BL@P) is designed for HCC‐targeted gene therapy. As prepared FT‐BL@P effectively suppress the growth of HCC cells and induces apoptosis both in vitro and in vivo. Combined with JPH203, a phase 2 L‐type amino acid transporter 1 (LAT‐1) inhibitor, FT‐BL@P achieves synergistic anti‐tumor effects in a xenograft HCC model, suggesting that the co‐delivery of CHRDL‐1 combined with JPH203 holds promise as a potential therapeutic strategy for HCC.

01 Dec 2024·Histology and histopathology

The role of CD98 heavy chain in cancer development.

Review

Author: Kim, Hyesung ; Park, Eunsun ; Yoon, Seokho ; Jang, Bogun

The glycoprotein CD98, or CD98 heavy chain (CD98hc), encoded by the SLC3A2 gene, plays a crucial role in cancer development and progression. CD98hc, forming heterodimeric complexes with various light chains, regulates neutral amino acid transport across cell membranes. The intricate interplay between CD98hc, integrins, and amino acid transporters shapes the tumor microenvironment and contributes to tumor growth. Elevated expression of CD98hc in various cancers correlates with poor prognosis, making it a potential prognostic marker. In colorectal cancer, CD98hc emerges as a potential therapeutic target, along with its partner LAT1, and inhibitors like JPH203 exhibit promise in preclinical studies. Targeting CD98hc/LAT1, alone or with conventional therapies, shows promise in inhibiting tumor growth. This review focuses on elucidating the multifaceted roles of CD98hc and its partner LAT1 in cancer, particularly its involvement in amino acid transport, signaling pathways, and its prognostic relevance in cancer.

01 Nov 2024·Biochemical and Biophysical Research Communications

JPH203 alleviates peritoneal fibrosis via inhibition of amino acid-mediated mTORC1 signaling

Article

Author: Dai, Junhao ; Yu, Zanzhe ; Zhang, Xuemei ; Wu, Tiangang ; Li, Jiayang ; Ning, Fengling ; Zhu, Nan ; Liu, Xin

BACKGROUND AND AIMSThe mesothelial-mesenchymal transition (MMT) of mesothelial cells has been recognized as a critical process during progression of peritoneal fibrosis (PF). Despite its crucial role in amino acid transport and metabolism, the involvement of L-type amino acid transporter 1 (LAT1) and the potential therapeutic role of its inhibitor, JPH203, in fibrotic diseases remain unexplored. Considering the paucity of research on amino acid-mediated mTORC1 activation in PF, our study endeavors to elucidate the protective effects of JPH203 against PF and explore the involvement of amino acid-mediated mTORC1 signaling in this context.METHODSWe established the transforming growth factor beta 1 (TGF-β1) induced MMT model in primary human mesothelial cells and the peritoneal dialysis fluid (PDF) induced PF model in mice. The therapeutic effects of JPH203 on PF were then examined on these two models by real-time quantitative polymerase chain reaction, western blotting, immunofluorescence staining, Masson's trichrome staining, H&E staining, picro-sirius red staining, and immunohistochemistry. The involvement of amino acid-mediated mTORC1 signaling was screened by RNA sequencing and further verified by western blotting in vitro.RESULTSLAT1 was significantly upregulated and JPH203 markedly attenuated fibrotic phenotype both in vitro and in vivo. RNA-seq unveiled a significant enrichment of mTOR signaling pathway in response to JPH203 treatment. Western blotting results indicated that JPH203 alleviates PF by inhibiting amino acid-mediated mTORC1 signaling, which differs from the direct inhibition observed with rapamycin.CONCLUSIONJPH203 alleviates PF by inhibiting amino acid-mediated mTORC1 signaling.

100 Deals associated with Nanvuranlat

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Biliary Tract Neoplasms	Phase 3	Japan	J-Pharma Co., Ltd.	-
Colorectal Cancer	Phase 2	United States	J-Pharma Co., Ltd.	-
Colorectal Cancer	Phase 2	Japan	J-Pharma Co., Ltd.	-
Renal Cell Carcinoma	Phase 1	Japan	J-Pharma Co., Ltd.	-
Cholangitis, Sclerosing	Preclinical	Japan	J-Pharma Co., Ltd.	01 Feb 2025

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


JPRN-UMIN000034080 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Biliary Tract Neoplasms	104	Nanvuranlat	(dcnaygnlfv): HR = 0.439 (95% CI, 0.2254 - 0.8535), P-Value = 0.0131 View more	Positive	26 May 2023
				placebo
JPRN-UMIN000034080 (ASCO_GI2023) Manual	Phase 2	Biliary Tract Neoplasms	106	nanvuranlat	(raoekwvkgo) = significant improvement cyyspchxdj (alflctdtbe ) Met	Positive	24 Jan 2023
				placebo
JPRN-UMIN000016546 (ASCO2018)	Phase 1	HR-positive/HER2-low Solid Tumors	-	JPH203	(szgfaradnq) = Common treatment-related adverse events were increased ALT/AST, malaise, nausea, hypertension, and grade 1 or grade 2 fevers. ikcjuxhiez (yczcxgfzyw ) View more	Positive	01 Jun 2018