TGX-221 / Enzo, Wuhan University, Pfizer - LARVOL DELTA

Integrated multi-omics analysis reveals dendritic cell centered regulatory networks and therapeutic targets in necrotizing enterocolitis. (PubMed, Front Immunol) - "In an inflammation model of LPS stimulation using mouse intestinal organoids, TGX221 suppressed inflammatory cytokine induction and partially restored tight junction protein expression. These findings highlight DCs as central mediators of NEC-associated immune communication and identify ALPK2 as a potential regulator of intestinal inflammation and epithelial barrier dysfunction, supporting ALPK2 as a candidate NEC-associated regulator with potential therapeutic implications."

Journal • Gastrointestinal Disorder • Inflammation • Inflammatory Bowel Disease • ALPK2 • TACC3

SOS1-RAS-RAF signaling sensitizes platelet responsiveness via GPVI and PAR-1 (ISTH 2026) - "At high convulxin and TRAP-6 concentrations, inhibition of SOS1-RAS interaction, (Bay-293), BRAF (PLX4032) or BRAF dimerization (PLX8394) partially reduced platelet αIIbβ3 integrin activation, P-selectin/CD63 surface expression, aggregation and phosphatidylserine exposure in a dose dependent manner...Synergistic inhibition of convulxin-induced platelet activation and MEK1/2 S217/221 phosphorylation was observed by combined blocking of BRAF and PKC isoforms (GF109203X), P2Y 12 receptor (AR-C69931), PI3K-p110β (TGX-221) and ASK1 (selonsertib), respectively...This project was supported by the German Research Foundation (DFG). DOI*10.1016/j.rpth.2026.105258"

ARAF • CD63 • MAP2K1

A brain-enriched Extracellular Vesicles liquid biopsy links bipolar disorder biology to drug candidates through Connectivity Map Analysis (CINP 2026) - "CMap nominated potential therapeutics including dinaciclib (CDK inhibitor), TGX-221 (PI3Kβ inhibitor), fatostatin (SREBP inhibitor), KW-2449 (FLT3/Aurora kinase inhibitor), acalabrutinib (BTK inhibitor), and the muscarinic M3 antagonists otilonium and diphemanil; all nominated hits met FDR-adjusted p < 0.05. Plasma NCAM1-positive EV transcriptomes capture brain-enriched signals and provide a scalable, minimally invasive readout for biomarker discovery and biological stratification in mood disorders. Crucially, integrating this liquid-biopsy signature with CMap establishes an end-to-end, mechanism-aware route from blood to actionable drug hypotheses—prioritizing compounds predicted to counteract immune-inflammatory, proliferative, and metabolic programs activated in BD. These candidates warrant independent validation in larger cohorts and experimental models and may enable a pragmatic path toward precision repurposing and longitudinal monitoring of treatment-related..."

Biopsy • Liquid biopsy • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • FLT3 • NCAM1 • PIK3CB

A Macrophage/Monocyte-Related Four-Gene Signature for Prognostic Assessment of Uveal Melanoma: BTBD6, C2CD4B, CCL24, and S100A4. (PubMed, Hum Mutat) - "A significant negative correlation between RiskScore and the IC50 of XMD8-85, lapatinib, roscovitine, salubrinal, bexarotene, LFM-A13, FTI-277, and TGX221 chemotherapeutic agents was further noticed. In this study, we computationally identified genes associated with both disease progression and macrophage/monocyte-related characteristics in UVM and constructed a prognostic risk model with predicted immune infiltration patterns. These findings generate testable hypotheses that may inform future experimental studies on the immune mechanisms underlying UVM."

Biomarker • Gene Signature • Journal • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8 • S100A4

Combined inhibition of CDK4/6 and AKT is highly active against the luminal androgen receptor (LAR) subtype of triple negative breast cancer (TNBC) (AACR 2024) - "Enzalutamide, an AR antagonist, exerted no growth inhibitory activity (IC50, 15-25 μM)...The combination of palbociclib+capivasertib synergistically inhibited the proliferation of MDAMB453 and MFM223 cells (synergistic scores 7.34, p=5.81-11, and 4.78, p=0.012, respectively) better than palbociclib+alpelisib...PI3Kβ inhibitors (TGX221, GSK2636771) did not block AKT substrate upregulation, suggesting PI3Kβ does not mediate adaptive responses...Treatment with palbociclib and the PDGFRβ small-molecule antagonist CP673451 arrested LAR TNBC growth similar to palbociclib+capivasertib, suggesting an adaptive response involving PDGFRβ signaling. In conclusion, this study supports the clinical testing of the palbociclib and capivasertib combination for LAR TNBC patients and reveals adaptive responses after palbociclib treatment through PDGFRβ signaling."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1S1 • AR • CDK4 • PDGFRB • PIK3CA • PIK3CB • STAT3

Mesenchymal stem cells ameliorate Sjögren disease by suppressing B cells through the Pik3cb/Akt/mTOR pathway. (PubMed, Front Immunol) - "Systematic investigation of the role of Pik3cb in MSC therapy and B cell regulation revealed that MSC administration and pharmacological inhibition of Pik3cb (using TGX-221) significantly attenuated SjD progression...In conclusion, this study provides mechanistic evidence that MSC therapy mitigates B cell dysfunction in SjD through the Pik3cb/Akt/mTOR pathway. Furthermore, our data identified Pik3cb as a hitherto unrecognized molecular target in SjD pathogenesis, suggesting that its pharmacological inhibition may represent a promising complementary therapeutic avenue for SjD meriting further investigation."

Journal • Fibrosis • Immunology • Sjogren's Syndrome • IFNG • IL10 • IL4 • IL6 • PIK3CB • TGFB1

Multi-omics profiling of ACOX3 unveils pan-cancer clinical biomarker potential. (PubMed, Comput Biol Chem) - "ACOX3 represents a dual diagnostic and prognostic biomarker with broad pan-cancer relevance, exhibiting distinct immune correlates and therapeutic potential."

Biomarker • Journal • Pan tumor • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

A fibroblast-specific gene signature as a therapeutic target for glioblastoma developed based on the characteristics of tumor microenvironment. (PubMed, Eur J Med Res) - "We constructed a RiskScore model for predicting the survival outcomes based on fibroblasts-related genes. These findings highlighted the role of fibroblasts in GBM development and offered six potential therapeutic targets (VWA1, DUSP6, LOXL1, IGFBP4, CYGB, and ZIC3) for GBM treatment. Additionally, immune infiltration analysis and drug sensitivity prediction further supported the model's utility in guiding personalized treatment of GBM."

Biomarker • Gene Signature • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • DUSP6

NK CELL-RELATED GENE-DRIVEN NOVEL MOLECULAR SUBTYPING AND PROGNOSTIC MODEL FOR WILMS TUMOR: UNCOVERING THE THERAPEUTIC POTENTIAL OF TGX-221 AND BIOMARKER ROLE OF HS2ST1 (SIOP 2025) - "Additionally, TGX-221 emerged as a promising therapeutic candidate, while a prognostic signature based on NKGs was established, highlighting HS2ST1 as a key biomarker with potential clinical applications. Future efforts aim to translate these findings into clinical practice."

Biomarker • IO biomarker • Nephrology • Oncology • Solid Tumor • Wilms Tumor • NRAS • PPP3CA

NK cell-related genes-driven novel molecular subtyping and prognostic signatures for Wilms tumor: uncovering the therapeutic potential of TGX-221 and biomarker role of HS2ST1. (PubMed, Front Oncol) - "Moreover, TGX-221 represents a promising novel therapeutic candidate, while HS2ST1 serves as a potential prognostic biomarker. These findings collectively provide tools for risk stratification and targeted therapy, advancing precision oncology for WT."

Biomarker • Journal • Nephrology • Oncology • Solid Tumor • Wilms Tumor • PPP3CA

NK cell-related genes-driven novel molecular subtyping and prognostic signatures for Wilms tumor: uncovering the therapeutic potential of TGX-221 and biomarker role of HS2ST1 (Front Oncol) - "TGX-221 significantly inhibited the malignant progression of WT through a dual-action mechanism: blocking the key oncogenic Wnt/β-catenin signaling pathway and sensitizing tumor cells to NK cell-mediated cytotoxicity."

Biomarker • Preclinical • Wilms Tumor

Role and Therapeutic Potential of miR-301b-3p in Regulating the PI3K-AKT Pathway via PIK3CB in Eosinophilic Chronic Rhinosinusitis. (PubMed, J Inflamm Res) - "The role of PIK3CB was assessed using the PIK3CB inhibitor TGX-221...miR-301b-3p regulates type 2 inflammation and EMT in ECRS by targeting PIK3CB and modulating the PI3K-AKT pathway, suggesting both miR-301b-3p and PIK3CB as promising therapeutic targets. Given the limited sample size of this study, we plan to expand our cohort and implement a longitudinal follow-up design to monitor dynamic changes in miR-301b-3p expression and their relationship to disease progression."

Journal • Inflammation • Otorhinolaryngology • Respiratory Diseases • Sinusitis • PIK3CB

Integrated single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma. (PubMed, Transl Cancer Res) - "Additionally, a higher myCAF score was related to the higher half-maximal inhibitory concentration (IC50) values of D-4476, GW-583340, spautin-1, and VER-155008, and the lower IC50 values of JTE-607, TG100-115, ML320, and TGX-221. This study, which was based on single-cell and bulk RNA-seq analyses, showed the plasticity and metabolic heterogeneity of CAFs in HNSCC. Our findings may contribute to understandings of the immunotherapy response in HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs

Double Swords in One: Novel Selective PI3K/110β PROTAC Degraders for the Treatment of Multidrug-Resistant Cancer by Activating ERS and Inhibiting P-gp. (PubMed, J Med Chem) - "Herein, we describe the design, synthesis, and structure-activity relationship studies of a series of small-molecule PI3K/110β PROTACs degraders by combining the selective inhibitor TGX221 of PI3K/110β with VHL ligands...Meanwhile, the expression and activity of P-glycoprotein were significantly inhibited, leading to a strong synergistic antitumor effect with adriamycin or cisplatin...In vivo studies also verified that the two degraders inhibited the growth of MCF-7/ADM xenograft tumors with high safety. Hence, this study and further optimization of these PI3K/110β PROTAC degraders have broad prospects for the development of new cancer therapies."

IO biomarker • Journal • Oncology • Targeted Protein Degradation • PTEN

Folate receptor-targeted pH-sensitive liposomes loaded with TGX-221 against prostate cancer by inhibiting PI3K/110β signaling. (PubMed, Nanoscale Adv) - "Meanwhile, in vitro and in vivo experiments suggested that FA-Lip-TGX221 could activate the PERK-ATF4-CHOP signaling pathway by inhibiting PI3K/110β signaling in PCa, thus significantly promoting endoplasmic reticulum (ER) stress-mediated cancer cell death. In conclusion, FA-Lip-TGX221 is a promising nano-delivery vehicle for the treatment of PCa, and also provide valuable references for all tumors overexpressing folate receptors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ATF4

Migrasome-related ITGA5 for predicting prognosis, immune infiltration and drug sensitivity of hepatocellular carcinoma. (PubMed, Apoptosis) - "Drug sensitivity, molecular docking, and molecular dynamics analyses indicated that ITGA5 may enhance the sensitivity of HCC to drug TGX221. Finally, cell phenotype experiments confirmed that ITGA5 knockdown suppressed the proliferation, migration, and invasion of HCC cells, and while overexpression exacerbated malignant phenotypes. Our analyses showed that ITGA5 is a key migrasome-related gene involved in the proliferation and metastasis of HCC that has promise as a therapeutic target and candidate prognostic indicator."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ITGA5

Identification of Five NK Cell-Related Hub Genes in COPD Using Single-Cell RNA Sequencing Analysis. (PubMed, J Inflamm Res) - "The potential therapeutic agents for COPD may be zalcitabine, PP-2, PD-98059, and TGX-221 based on the CMap database prediction. We proposed that peripheral NK cells may play a role in the pathogenesis of COPD through bioinformatic analysis. These hub genes may provide insights into mechanistic research and new targets for new therapies in patients with COPD."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • ANXA1 • IGFBP7 • S100A6

Discovery of key molecular signatures for diagnosis and therapies of glioblastoma by combining supervised and unsupervised learning approaches. (PubMed, Sci Rep) - "Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • AURKA • CCNB2 • CDCA8 • CDK1 • CHEK1 • MCM10 • RAD51 • RAD51AP1 • TOP2A

The molecular background determines LSD1 inhibition sensitization of AML cells to gilteritinib and other kinase inhibitors (EACR 2024) - "Here, we hypothesise that the molecular background of AML determines the precise combinations of epigenetic and kinase targeting drugs that more effectively disrupt the dependencies that drive AML.Material and Methods Mega-erythroid (HEL, KMOE2 and CMK) and monocytic (MV4-11, P31 and NOMO1) AML cells were treated with the LSD1 inhibitor (LSD1i) GSK-2879552 for five days, followed by treatments with inhibitors of FLT3 (midostaurin and gilteritinib), MEK (trametinib), and PI3K (alpelisib, TGX-221, duvelisib, idelalisib and pictilisib aimed for α, β, δ/ɣ, δ and all isoforms) for three days. LSD1i reduced histone H3K79 methylation only in P31 cells and inhibitors of DOT1L, the enzyme that methylates H3K79, sensitized P31 cells to MEKi but not HEL cells to PI3Ki. These data suggest that the LSD1i induced sensitization to MEKi in P31 cells involves DOT1L, while the sensitization to PI3Kis in HEL cells may involve the lost of erythroid differentiation and energy metabolism..."

Acute Myelogenous Leukemia • DOT1L • FLT3 • PIK3CD

SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis. (PubMed, J Cancer) - "TGX-221, a PIK3CB-selective inhibitor, which can block this signaling transduction pathway, was found to inhibit the growth of GC cells and induce apoptosis in vitro, implying that it may act as a potential development agent for GC. These collective findings provide a new insight into PI3K/AKT signaling that SP1 may function as an upstream factor on PI3K, forming a new signaling axis to promote the progression of GC or other malignancies."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PIK3CB

Bioinformatics analysis identifies coagulation factor II receptor as a potential biomarker in stomach adenocarcinoma. (PubMed, Sci Rep) - "Drug sensitivity analysis demonstrated positive correlations between F2R and several drugs, including BEZ235, CGP-60474, Dasatinib, HG-6-64-1, Aazopanib, Rapamycin, Sunitinib and TGX221, while negative correlation with CP724714, FH535, GSK1904529A, JNK-9L, LY317615, pyrimidine, rTRAIL and Vinorelbine. In conclusion, this study underscores the significance of F2R as a potential biomarker in gastric adenocarcinoma, shedding light on its molecular mechanisms in tumorigenesis. F2R holds promise for aiding in the diagnosis, prognosis, and targeted therapy of STAD."

Biomarker • Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Thrombosis • F2R • TGFB1

Overcoming temozolomide resistance in glioblastoma through selective inhibition of phosphoinositide 3-kinase catalytic subunit. (ASCO 2023) - "Newly cultured wild-type cells were treated with IC50 doses of selective p110β inhibitor TGX-221 and TMZ. Inhibition of p110β via CRISPR-Cas9 knockout or pharmaceutical blockade restores TMZ sensitivity in p110β-high glioblastoma cells and xenograft glioblastoma tumors. These results demonstrate the varying importance of PI3K catalytic subunits and necessitate further exploration into p110β as a potential drug target to overcome chemoresistance in glioblastoma."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • PIK3CA • PIK3CG

Advances in lung adenocarcinoma: A novel perspective on prognoses and immune responses of CENPO as an oncogenic superenhancer. (PubMed, Transl Oncol) - "CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients."

Journal • Immune Modulation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Glucose 6 phosphatase dehydrogenase (G6PD): a novel diagnosis marker related to gastrointestinal cancers. (PubMed, Am J Transl Res) - "G6PD is highly expressed in gastrointestinal cancers. It is a carcinogenic indicator related to prognosis and can be used as a potential diagnostic marker of gastrointestinal cancers, so as to provide new strategy for cancer treatment."

Journal • Biliary Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatocellular Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD276 • CD4 • G6PD • GAPDH • HHLA2 • TP53

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma. (PubMed, Cancers (Basel)) - "This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8