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)

+ [1]

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

100 Clinical Results associated with Sabutoclax

100 Translational Medicine associated with Sabutoclax

100 Patents (Medical) associated with Sabutoclax

Literatures (Medical) associated with Sabutoclax

01 Mar 2025·Environmental Toxicology

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

Article

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

AbstractBackgroundCervical 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).MethodsRNA‐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.ResultsWe 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.ConclusionThis 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: Fang, Kun ; Yan, Changsheng ; Luo, Meng ; Jiang, Suxiao ; Xu, Zhengjie

ObjectiveDisulfidptosis 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.MethodsMulti-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.ResultsAberrant 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.ConclusionCollectively, our findings depict a pan-cancer map of disulfidptosis to inform functional and therapeutic research.

01 Aug 2024·International Immunopharmacology

DNA damage response-related signatures characterize the immune landscape and predict the prognosis of HCC via integrating single-cell and bulk RNA-sequencing

Article

Author: Wu, Shaobo ; Shi, Yu ; Sun, Liankang ; Liu, Qingguang ; Yang, Ruida ; Li, Yue ; Li, Hanqi

BACKGROUNDThe occurrence and progression of hepatocellular carcinoma (HCC) are significantly affected by DNA damage response (DDR). Exploring DDR-related biomarkers can help predict the prognosis and immune characteristics of HCC.METHODSFirst, the single-cell RNA sequencing (scRNA-seq) dataset GSE242889 was processed and performed manual annotation. Then we found the marker genes of DDR-active subgroups based on "AUCell" algorithm. The "Limma" R package was used to identify differentially expressed genes (DEGs) between tumor and normal samples of HCC. The risk prognostic model was constructed by filtering genes using univariate Cox and LASSO regression analyses. Finally, the signatures were analyzed for immune infiltration, gene mutation, and drug sensitivity. Last but not least, KPNA2, which had the largest coefficient in our model was validated by experiments including western blot, MTT, colony formation and γ-H2AX assays.RESULTSWe constructed a prognostic model based on 5 DDR marker genes including KIF2C, CDC20, KPNA2, UBE2S and ADH1B for HCC. We also proved that the model had an excellent performance in both training and validation cohorts. Patients in the high-risk group had a poorer prognosis, different immune features, gene mutation frequency, immunotherapy response and drug sensitivity compared with the low-risk group. Besides, our experimental results proved that KPNA2 was up-regulated in liver cancer cells than in hepatocytes. More importantly, the knockdown of KPNA2 significantly inhibited cell variability, proliferation and promoted DNA damage.CONCLUSIONSWe innovatively integrated scRNA-seq and bulk RNA sequencing to construct the DDR-related prognostic model. Our model could effectively predict the prognosis, immune landscape and therapy response of HCC.

100 Deals associated with Sabutoclax

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	-	Sanford Burnham Prebys Medical Discovery Institute	-

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