PHA 793887 / Nerviano Medical Sciences - LARVOL DELTA

High-Throughput High-Plex Proteomic Profiling of Hepatocyte Toxicity to Oncologic Drug Compounds: A Platform for Toxicity Assessment, Immune Risk Prediction, and Drug Development Acceleration (SITC 2025) - "This allows for evaluation of both cytotoxic and immunomodulatory signatures, revealing potential off-target effects and mechanistic insights.Results Perturbation with tripolide, doxorubicin, and cobimetinib resulted in dose dependent cell toxicity, detected via increased levels of intracellular proteins such as GAPDH and Casp3 released into the supernatant, consistent with clinically observed hepatotoxicity...Of particular note is PHA-793887, a potential therapeutic candidate, which failed clinically due to unexpected hepatotoxicity, which here was captured in a pre-clinical in vitro model.We further demonstrated the platform's ability to identify likely irAEs through detection of dose dependent increases in key cytokines. Hepatocytes perturbed with Imatinib and Pomalidomide demonstrated increases in IL-6, IL-10, and IL-2, indicative of potential irAE and consistent with published literature for these drugs.Conclusions High-throughput high-plex proteomic analysis of..."

Oncology • CASP3 • GAPDH • IL10 • IL2 • IL6 • LGALS1 • ST6GAL1

TGF-β1-Induced Phenotypic Switch in Endothelial and Mesenchymal Plasticity: The Role of CDK5 (AHA 2025) - "CDK5's role was evaluated using three inhibitors: PHA793887 (commercial), Compound-1 (kinases-promiscuous), and TK22 (novel, reversible)...TGF-β1 induces EndMT in mLECs via the CDK5 pathway. Inhibition of CDK5, particularly with the novel compound TK22, effectively halts and reverses EndMT, offering a promising therapeutic avenue for treating PAH and related vascular pathologies."

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases • TGFB1

CDK5 Inhibition Attenuates Nitration Stress-induced Endothelial-to-Mesenchymal Transition (ATS 2025) - "Our findings demonstrate that the CDK5 pathway plays a significant role in mediating nitration induced EndMT. Inhibition of CDK5 not only mitigates these changes but also underscores the potential of CDK5 inhibitors as therapeutic agents for pathologies related to mesenchymal transformation, including PAH."

Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CD31 • CDH2 • CDK5 • PECAM1

Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer. (PubMed, Front Immunol) - "Together, these data support FRS positively correlates with poor prognosis and therapy resistance. The PHA-793887 could be a potential FRS inhibitor to improving the effectiveness of CRC management via bolstering antitumor immunity."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • FGFR

SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity. (PubMed, Protein Pept Lett) - "SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients."

Journal • Breast Cancer • Endocrine Cancer • Eye Cancer • Melanoma • Microsatellite Instability • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Uveal Melanoma • MSI

Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation. (PubMed, Biochem J) - "We identified 13 compounds - ABT-578, AR-A014418, AZD1480, AZD5363, Idelalisib,  Ipatasertib, LJ1308, PHA-793887, Rapamycin, Ridaforolimus, SMI-4a,  Temsirolimus and Tideglusib - each of which inhibits mTOR signalling or regulators thereof, and blocked constitutive cell death executed by R30E MLKL. Our study implicates mTOR signalling as an auxiliary factor in promoting transport of activated MLKL oligomers to the plasma membrane, where they accumulate into hotspots that permeabilise the lipid bilayer to cause cell death."

IO biomarker • Journal

Pancancer Analysis of NSUN2 with a Focus on Prognostic and Immunological Roles in Endometrial Cancer. (PubMed, Reprod Sci) - "Notably, higher levels of NSUN2 expression have been linked to a reduced response to certain chemotherapeutic agents, including PHA-793887...Our study highlights the potential of NSUN2 as a key oncogene and its promising role as a therapeutic target as well as a prognostic biomarker for endometrial cancer. This underscores its potential importance in predicting responses to immunotherapy."

IO biomarker • Journal • Pan tumor • Tumor mutational burden • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • NSUN2 • TMB

Integrated transcriptomic analysis systematically reveals the heterogeneity and molecular characterization of cancer-associated fibroblasts in osteosarcoma. (PubMed, Gene) - "Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME."

Heterogeneity • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CAFs • CD74 • CXCL14 • HLA-DRA • HLA-DRB1

A precise prognostic signature in CTNNB1-mutant hepatocellular carcinoma: Prognosis prediction and precision treatment exploration. (PubMed, Heliyon) - "Subsequently, we suggested that AT-7519 and PHA-793887 might be potential drug agents for high-risk patients. Besides, we explored the potential drug targets and agents for patients with high risk. Our findings offered a fresh idea for personalized prognosis management in HCCs with CTNNB1 mutations and threw new insight for precise treatment in HCCs as well."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CTNNB1

Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma. (PubMed, Cancers (Basel)) - "Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKA • CCNB1 • CDK1 • RRM2 • TOP2A

Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases. (PubMed, Cancers (Basel)) - "Aiming at attenuation of general toxicity of low selectivity compounds, we herein explored the new chemotype of imidazole-4-N-acetamide substituted derivatives of the pan-CDK inhibitor PHA-793887...This methodology allows for the demonstration of a good correlation between the calculated parameters of interaction of 1-4 with individual targets and the values of inhibitory potencies in in vitro kinase assays. We provide evidence in support of NEQ thermodynamics as a time sparing, precise, and productive approach for generating chemical inhibitors of clinically relevant anticancer targets."

Journal • Oncology • CDK1

Three candidate anticancer drugs were repositioned by integrative analysis of the transcriptomes of species with different regenerative abilities after injury. (PubMed, Comput Biol Chem) - "Based on these gene signatures, we investigated 3 small compounds, namely cucurbitacin I, BMS-754807, and PHA-793887 as potential candidates for the treatment of cancer. Future studies on the mechanisms associated with the revealed gene signatures and anticancer effects of these three small compunds would allow scientists to develop therapeutic approaches to combat cancer. This research contributes to the evaluation of mechanisms and gene signatures that either limit or cause cancer, and to the development of new cancer therapies by establishing a link between regeneration and carcinogenesis."

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

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates. (PubMed, BMC Bioinformatics) - "Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes."

Biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • EZH2 • KRAS

Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer. (PubMed, Front Immunol) - "Additionally, the higher the expression of ESPL1 in organoids, the greater the sensitivity to PHA-793887, PAC-1, and AZD7762. Taken together, our study provides evidence that ESPL1 may implicate tumorigenesis and disease progression across multiple cancer types, highlighting its potential utility as both a prognostic indicator and therapeutic target."

Journal • Pan tumor • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Bioinformatics Identification of Therapeutic Gene Targets for Gastric Cancer. (PubMed, Adv Ther) - "Overall, we suggest that these hub genes can be used as biomarkers and novel targets for GC. FBN1 may be associated with drug resistance in gastric cancer."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FBN1

Mitochondrial Aldehyde Dehydrogenase 2 Represents a Potential Biomarker of Biochemical Recurrence in Prostate Cancer Patients. (PubMed, Molecules) - "We found that ALDH2 might serve as a potential biomarker predicting biochemical recurrence for PCa patients."

Biomarker • Journal • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor • ALDH2 • CD8 • CD96 • NRP1

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis. (PubMed, Front Immunol) - "The drug sensitivity analysis screens out potential therapeutic agents associated with CLEC5A expression, including FR-180204, Tivozanib, OSI-930, Linifanib, AC220, VNLG/124, Bexarotene, omacetaxine mepesuccinate, narciclasine, leptomycin B, PHA-793887, LRRK2-IN-1, and CR-1-31B. CLEC5A overexpresses in multiple cancers in contrast to normal tissues, and high CLEC5A expression predicts poor prognosis of patients and immune infiltration. CLEC5A is a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy."

Biomarker • Journal • Pan tumor • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • CAFs • MSI • TMB

Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance. (PubMed, Front Oncol) - "RT-qPCR analysis confirmed the effect of AICAR, AT-7519, PHA-793887 and PI-103 on the mRNA levels of GSTM3/4. GSTM3 was negatively correlated with OC prognosis, and associated with OC chemoresistance and immune escape. This gene may serve as potential prognostic biomarkers and therapeutic target for OC patients."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • GSTM1 • GSTM5 • GSTP1

A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer. (PubMed, J Transl Med) - "We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis."

Journal • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor • ALDH2 • PD-L2

Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer. (PubMed, Bioinform Biol Insights) - "On the contrary, high mRNA expressions of CBL, FYN, LRKK2, and SOCS2 were associated with a significantly better prognosis. Furthermore, our drug target analysis for these hub genes suggests a potential use of Trichostatin A, Pracinostat, TGX-221, PHA-793887, AG-879, and IMD0354 antineoplastic agents to reverse the expression of these DEGs in NSCLC patients."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • CDC20 • CDK1 • CDKN2A • EZH2 • FYN • SOCS2

Biomarkers for predicting abiraterone treatment outcome and selecting alternative therapies in castration-resistant prostate cancer. (PubMed, Clin Pharmacol Ther) - "This approach identified 3 drugs, including TOP2 inhibitor mitoxantrone, CDK4/6 inhibitor palbociclib, and pan-CDK inhibitor PHA-793887. Moreover, we identified 11 genes targeted by all three drugs that were associated with worse outcomes in both the PROMOTE and Stand Up To Cancer cohorts. This 11 gene panel might also function as biomarkers to select the 3 alternative therapies for this subgroup of CRPC patients, warranting further clinical investigation."

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

A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer. (PubMed, Front Oncol) - "PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887. We concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa."

Journal • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Prostate Cancer • Solid Tumor • CD2 • CD8 • HAVCR2 • PD-L2 • SFRP4 • SPP1

Biological and Clinical Significance of PIM1 Genetic Alterations in Diffuse Large B-Cell Lymphoma (ASH 2021) - "We further found that compared to patients with low-risk score, patients with high-risk score had higher sensitivity to some drugs of targeting the immune microenvironment, including TGFβ receptor inhibitors SB525334 ( P <0.0001) and SB505124 ( P <0.0001) and immunomodulator Lenalidomide ( P =0.041), as well as NF-κB inhibitors Parthenolide ( P <0.0001) and TPCA-1 ( P <0.0001) and JAK inhibitors Ruxolitinib ( P =0.014) and TG101348 ( P =0.0053), accompanying with significantly lower IC50 values. In addition, another common chemotherapeutic drug Gemcitabine was also predicted to be more sensitive for patients with high-risk score ( P =0.047). Other targeted drugs such as Aurora kinase inhibitors VX-680 ( P <0.0001) and ZM-447439 ( P =0.014), Bcl-2 inhibitors Obatoclax Mesylate ( P =0.00036) and Navitoclax ( P <0.0001), and CDK inhibitors Roscovitine ( P =0.0012), AT-7519 ( P =0.0033), PHA-793887 ( P <0.0001) and THZ2-49 ( P =0.0053) also exhibited..."

Clinical • IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B • IL17A • MYD88 • PIM1 • PRDM1 • TGFB1

Interpretable deep recommender system model for prediction of kinase inhibitor efficacy across cancer cell lines. (PubMed, Sci Rep) - "The interpretability analysis identifies 67 biological processes that drive the cell line sensitivity to particular compounds. Detailed case studies are shown for PHA-793887, XMD14-99 and Dabrafenib."

Journal • Preclinical • Oncology

Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma. (PubMed, Aging (Albany NY)) - "Western blotting and enzyme-linked immunosorbent assays indicated that CDK1 expression in osteosarcoma cells declined with increasing PHA-793887 concentrations. These results suggest that PHA-793887 could be a promising new treatment for osteosarcoma."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CDK1