Delving into the Latest Updates on Sabutoclax with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BI-97C1, ONT 701, ONT-701

Target

Bcl-2 x Bcl-xl x Mcl-1

Action

inhibitors, stimulants

Mechanism

Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors), Bcl-xl inhibitors(Apoptosis regulator Bcl-X inhibitors), Mcl-1 inhibitors(Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Prostatic Cancer

Originator Organization

Sanford Burnham Prebys Medical Discovery Institute

Active Organization-

Inactive Organization

Sanford Burnham Prebys Medical Discovery Institute

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC42H40N2O8

InChIKeyRAYNZUHYMMLQQA-UHFFFAOYSA-N

CAS Registry1228108-65-3

The ribophorin family, including RPN1, has been associated with tumor progression, but its specific role in pan‐cancer dynamics remains unclear. Using data from TCGA, GTEx, and Ualcan databases, we investigated the relationship of RPN1 with prognosis, genomic alterations, and epigenetic modifications across various cancers. Differential analysis revealed elevated RPN1 expression in multiple cancer types, indicating a potential prognostic value. Amplification was the predominant mutation type of RPN1 in pan‐cancer, with notable correlations with DNA methylation and copy number variation. Gene set variation analysis identified RPN1's involvement in cancer development, immunity, and metabolism. Additionally, RPN1 expression correlated with the tumor microenvironment, immune response factors, and response to anti‐tumor therapies. Functional validation in triple‐negative breast cancer, glioblastoma, and bladder cancer cell lines demonstrated the role of RPN1 in tumor cell proliferation and migration. Our findings highlight RPN1 as a potential biomarker for cancer diagnosis and treatment response in pan‐cancer therapy.

01 Mar 2025·ENVIRONMENTAL TOXICOLOGY

Revolutionizing prognosis: Introducing cell death index (CDI) as a powerful prognostic tool for CSCC patients

Article

Author: Lou, Jun ; Zhang, Ke ; Yu, Qingqing ; Tang, Rongjun ; Li, Lingdi ; Yao, Qing

Abstract:

Background:

Cervical squamous cell carcinoma (CSCC) threatens the body health of women worldwide. This study aimed to foster a new concept of prognostic indicator named cell death index (CDI).

Methods:

RNA‐seq and scRNA‐seq datasets were downloaded from the GEO and TCGA database as the training and validation cohorts. Programmed cell death (PCD)‐related gene signatures were obtained from published research. The construction of prognostic model was performed based on CDI value. Patients with CSCC were divided into high‐ and low‐CDI groups. We explored the differences in overall survival time, immune infiltration, mutation status, and drug sensitivity between high and low CDI groups by R software.

Results:

We constructed prognostic model to calculate the CDI value with 23 genes. Patients with high CDI have shorter survival time than those with low CDI. CDI was considered a risk factor compared to other characteristics. The nomogram model estimated overall survival (OS) at 1, 3, and 6 years, with age, Stage, and CDI, indicating the accuracy of the model in predicting 1‐, 3‐, and 6‐year survival rates. CDI values were negatively correlated with most immune checkpoint genes. We measured the significant drug sensitivity of Mitoxantrone, Sabutoclax, Sepantronium bromide, Topotecan, BI‐2536, and BMS‐754807 between high‐ and low‐CDI groups with significant correlation.

Conclusion:

This investigation constructed a novel effective prognostic indicator of CDI in patients with CSCC and identified potential genes associated with cell death that could be targeted for prognosis and treatment of CSCC.

01 Nov 2024·Heliyon

Pan-cancer landscape of disulfidptosis across human tumors

Article

Author: Xu, Zhengjie ; Fang, Kun ; Luo, Meng ; Jiang, Suxiao ; Yan, Changsheng

Objective:

Disulfidptosis is a newly discovered disulfide stress-induced cell death form. Clinical significance and biological mechanisms of disulfidptosis in human cancers need to be further elucidated. Thus, this study was designed to characterize pan-cancer landscape of disulfidptosis across human tumors.

Methods:

Multi-omics features (transcriptomics, genomics, and DNA methylation) of disulfidptosis genes were investigated in TCGA pan-cancer cohorts. A disulfidptosis score system was defined across human tumors via ssGSEA. The activity of classical oncogenic pathways and hallmarks of cancer as well as the infiltration of immunocyte subpopulations were estimated, respectively. Drug sensitivity was inferred, and immune checkpoint blockade (ICB) response was evaluated in an independent cohort IMvigor210. ACHN, CAL-27, and NCI-H23 cells were transiently transfected with GYS1 siRNAs, and cell apoptosis and proliferation were measured through TUNEL and EdU assays, respectively.

Results:

Aberrant mRNA expression and DNA methylation of disulfidptosis genes as well as their genomic alterations were found in human tumors. The disulfidptosis score was utilized for quantifying the activity of disulfidptosis, which enabled to estimate patient prognosis. The disulfidptosis score presented positive correlations to angiogenesis and EMT, indicating the role of disulfidptosis in mediating tumor malignant features. Moreover, the score was negatively linked with infiltrating immune and stromal cells in the immune microenvironment. In the ICB cohort, shorter survival time was observed in patients with high disulfidptosis score, indicating the potential of disulfidptosis score in influencing clinical benefits from ICB. Additionally, tumors with low disulfidptosis score exhibited higher sensitivity to a few small molecular compounds, e.g., Sabutoclax, PRIMA-1MET, BIBR-1532, and Elephantin. Knockdown of disulfidptosis gene GYS1 effectively hindered tumor progression.

Conclusion:

Collectively, our findings depict a pan-cancer map of disulfidptosis to inform functional and therapeutic research.

100 Deals associated with Sabutoclax

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