tozasertib (MK-0457) / Vertex, Merck (MSD) - LARVOL DELTA

Scalable Synthesis of a Masked Thiophenol as an Air-Stable, Odorless Intermediate to the Aurora Kinase Inhibitor Tozasertib (VX-680). (PubMed, Org Process Res Dev) - "Here, we report the process optimization of this methodology for the synthesis of a key intermediate to kinase inhibitor tozasertib (VX-680). The corollary is a reduction in catalyst loading to 0.5 mol %, elimination of NMP solvent, and introduction of a direct crystallization, giving 95% yield on a 100 g scale."

Journal

A Transient Receptor Potential-related Gene Model for the Prognostic Assessment and Drug Sensitivity Prediction in Osteosarcoma. (PubMed, Curr Med Chem) - "The TRG-related gene model may assist in the prediction of prognosis and drug sensitivity in OS, thereby contributing to the development of relevant therapies."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • KRAS • LASP1 • MYC

Development and Validation of an m6A-Derived Prognostic Signature in Lung Adenocarcinoma. (PubMed, J Cancer) - "The signature independently predicted prognosis (AUC: 0.70-0.84) and treatment response: LR patients favored immunotherapy (lower TIDE, higher IPS), while HR patients were sensitive to chemotherapy (e.g., Bosutinib, Tozasertib). This transcriptome-derived m6A-associated prognostic model can effectively predict clinical survival outcomes and therapeutic response in LUAD patients. Combined with immune landscape, genomic mutation profiles and single-cell transcriptomic evidence, this signature provides a reliable basis for personalized risk stratification and rational treatment choice."

IO biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CSMD3 • LAG3 • PD-1 • TMB

Combination Treatment Targeting Cancer Stem Cell Subpopulation Reverting Chemoresistance in Germ Cells Tumors (EACR 2026) - "Material and A broad panel of parental and cisplatin-resistant (CisR) isogenic GCT cell lines was analyzed for TACSTD2 (TROP-2) expression by RT-qPCR, and sensitivity to sacituzumab govitecan was assessed at day 3 using an endpoint luminescence assay. To explore strategies for overcoming chemoresistance, combination treatments were performed with a panel of targeted pathway inhibitors affecting cell cycle, DNA damage response, transcriptional regulation, and oncogenic signaling (Tuvusertib [CDK7 inhibitor], Ceralasertib [ATR inhibitor], Adavosertib [WEE1 inhibitor], Simvastatin, Copanlisib, ABVV-744, Cyclosporin A, Dasatinib, Crizotinib, Tozasertib, Alpelisib, Selumetinib) to evaluate potential synergistic effects.Result and We focused on the transmembrane glycoprotein TROP-2 (trophoblast cell surface antigen 2), involved in proliferation, migration, and invasiveness, which is overexpressed in multiple solid tumors... Our findings support further investigation of..."

Cancer stem • Clinical • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • TACSTD2

Multi-omics analysis positions DNA2 at the interface of genome integrity programs and tumor behavior in pan-cancer. (PubMed, Funct Integr Genomics) - "According to the pharmacogenomic analysis from GDSC2 dataset, tumor cells that express higher DNA2 are more sensitive to Tozasertib, and Daporinad. DNA2 is at the core of several interrelated modules, including flap processing, telomerase extension, and cell-cycle progression, according to the enrichment study. These findings have suggested DNA2 as a therapeutic vulnerability in cancer, a context-dependent biomarker with implications for treatment response, prognosis, and immunity."

Journal • Pan tumor • Adrenal Cortex Carcinoma • Endometrial Cancer • Genito-urinary Cancer • Mesothelioma • Oncology • Solid Tumor • DNA2

Development and validation of an m6A and autophagy related lncRNAs signature for predicting survival and modulating the immune microenvironment in esophageal squamous cell carcinoma. (PubMed, Front Immunol) - "Pharmacogenomic analysis identified nine compounds (Shikonin, Bicalutamide, Bryostatin-1, Epothilone-B, JNK-9L, LFM-A13, QS11, VX-680, and Z-LLNle-CHO) exhibiting differential sensitivity between the dichotomous risk strata. This study yields findings that hold significant clinical implications for refining prognostic stratification and deciphering the immune landscape in ESCC. Moreover, they offer novel perspectives that may pave the way for more precise prognostic assessment and the formulation of targeted therapeutic interventions."

Biomarker • IO biomarker • Journal • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • LAIR1 • TNFRSF18

Construction of an actin cytoskeleton-related gene signature for predicting prognosis and therapeutic response in glioblastoma: based on machine learning. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis indicated that tozasertib, savolitinib, AZD4547, IWP-2, and GSK591 may have potential therapeutic value. Multi-omics analyses revealed that these key genes are regulated by DNA methylation and transcription factor networks. The actin cytoskeleton-based gene signature serves as an independent indicator of poor prognosis and may support precise prognostic assessment and personalized therapeutic strategies for GBM."

Gene Signature • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • AKT1 • EGF • FGFR1 • PDGFRA • PI3K • PIP5K1A

Leveraging mitochondrial dynamics-related risk signatures to predict the prognosis and tumor microenvironment of lung adenocarcinoma. (PubMed, Discov Oncol) - "This work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment."

Biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP27A1 • HMGA2 • SLC2A3 • TMB

Tozasertib + cisplatin inhibits proliferation, migration, and induces apoptosis in esophageal carcinoma cells. (PubMed, Clin Transl Oncol) - "In summary, aurora kinase inhibitor combined with CDDP could suppress the ERK pathway to affect the biological process of esophageal carcinoma cells. Versus a simple drug, a drug combination could effectively inhibit the proliferation and migration of esophageal carcinoma cells, promote apoptosis, reduce angiogenesis, and induce cell cycle arrest."

Journal • Esophageal Cancer • Oncology • CASP3 • CCNB1 • MMP2 • MYC

Role of Anti-GD2 Targeted PEG-b-PLGA Nanoparticles in the Treatment of MYCN Driven Neuroblastoma. (PubMed, ACS Appl Bio Mater) - "Everolimus (EVER) and tozasertib (TOZA) encapsulated in NP and targeted with dinutuximab β (DTX-β). DTX-β/EVER-TOZA@PEG-b-PLGA may exert cytotoxic and apoptotic effects in NB. The use of targeted nanocarriers in NB treatment may enhance cytotoxic and apoptotic responses specifically in the tumor region."

Journal • Embryonal Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer. (PubMed, Int J Gen Med) - "Drug sensitivity analysis indicates that the RORC gene is responsive to agents such as VX-680, MG-132, and Sunitinib. Cell biology experiments have confirmed that RORC overexpression significantly diminishes the proliferation, invasion, and migration capabilities of gastric cancer cells. Integrating bioinformatics and cell biology experiments suggests that RORC, a gene associated with rhythm regulation, acts as a tumor suppressor gene that is underexpressed in gastric cancer, thereby serving as a potential biomarker and therapeutic target for this malignancy."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ARID1A • RORC • TP53

Integrative In Silico Multi-Omics Profiling of circRNA-Mediated ceRNA Networks Reveals Prognostic Biomarkers and Repurposed Therapeutic Candidates in Gastric Cancer. (PubMed, Int J Mol Sci) - "To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds-celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A-predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology."

Biomarker • Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • COL4A1 • IGF2BP3 • MMP14 • TGM2

A demethylation-driven gene signature predicts prognosis and therapeutic vulnerability in hepatocellular carcinoma. (PubMed, Sci Rep) - "Drug sensitivity prediction indicated that high-risk patients may respond better to agents such as Tozasertib and Navitoclax. This study establishes a robust, demethylation-driven six-gene signature that effectively stratifies HCC patients into distinct prognostic groups. The model integrates multi-omic insights into tumor biology and therapeutic vulnerability, providing a clinically actionable framework for personalized risk assessment and treatment planning in hepatocellular carcinoma."

Gene Signature • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CDC20 • G6PD • TP53

Identification and Underlying Mechanisms of Immune Cell- and Senescence-Related Biomarkers in Atrial Fibrillation (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban) - "Drug prediction analysis indicated that only MYLK had potential interactions with 3 drugs, among which Tozasertib exhibited the strongest binding affinity to MYLK, with a binding energy of －7.8 kcal/mol. RT-qPCR results showed that IGFBP2 mRNA expression was upregulated and MYLK mRNA expression was downregulated in myocardial tissue of rats in the AF group compared with the SR group (both P < 0.05). In this study, MYLK and IGFBP2 are identified as AF-related biomarkers, and their potential molecular mechanisms are elucidated, providing new theoretical insights into AF research."

Biomarker • Journal • Atrial Fibrillation • Cardiovascular • IGFBP2 • MYLK • TAF1

Identification of 2 Ubiquitin-Proteasome System-Related Subtypes in Esophageal Squamous Cell Carcinoma for Prognostic and Immunotherapeutic Response Prediction. (PubMed, J Immunother) - "Selumetinib, entinostat, and erlotinib were identified as candidate drugs for cluster 2, whereas tozasertib, alpelisib, and cediranib showed higher suitability for cluster 1. Ten potential biomarkers, 13 transcription factors, and 2 miRNAs were characterized. This study elucidates the role of UPS in ESCC progression and provides a framework for personalized treatment strategies."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • Targeted Protein Degradation • CD8 • TP53

Structure-based identification of Jervine as a potent dual-targeting inhibitor of cell cycle kinases. (PubMed, Front Pharmacol) - "Lastly, MMPBSA showed a higher negative free energy in the presence of Jervine than VX-680 when complexed with AURKB. Finally, our results suggest that Jervine is a potent, dual-targeting kinase inhibitor with favourable pharmacokinetic and therapeutic properties, warranting further experimental validation for anticancer drug development."

Journal • Oncology • AURKB • CDK1

Multiomics profiling Identifies MCMBP as a prognostic biomarker and a potential immune-related target in pancreatic ductal adenocarcinoma via the JAK-STAT3 pathway. (PubMed, Front Immunol) - "High MCMBP expression was ass-ociated with sensitivity to Gemcitabine combined with Paclitaxel, as well as small mo-lecules such as Tozasertib and Motesanib. Overexpression of MCMBP may serve as a prognostic biomarker and p-otential therapeutic target in PAAD. It drives PAAD progression by activating the JAK-STAT3 pathway to upregulate PD-L1."

Biomarker • IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD4

Utilizing a novel mitochondrial-related gene signature for predicting the prognosis and immunological impact in bladder cancer. (PubMed, Discov Oncol) - "This validated mitochondrial risk model delivers a clinically actionable biomarker for BLCA prognosis stratification and guides personalized therapeutic selection, enabling precision treatment intensification."

Gene Signature • IO biomarker • Journal • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • HSD3B1 • KLK6 • MAP1B • PYCR1 • TMB

A Novel BCR::ABL1 Rearrangement Harboring the Gatekeeper Mutation Drives Hyper-Kinase Activity Conferring Resistance to Ponatinib and Asciminib Combination Therapy (ASH 2024) - "These cell lines were subjected to dose-dependent proliferation assays with type-I (bosutinib, dasatinib, VX680, and BIRB796), type-II (imatinib, nilotinib, ponatinib, and ribastinib), and type-IV (asciminib) inhibitors. Interestingly, BCR : : ABL1b6a3 showed increased sensitivity to type-I inhibitors, yet all clinical type-I inhibitors are ineffective against T315I and other gatekeeper variants. Therefore, developing gatekeeper-selective type-I inhibitor is crucial to overcome clinical resistance."

Combination therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Functional characterization and clinical significance of IGSF8 in pan-cancer: an integrated bioinformatic and experimental study. (PubMed, Front Immunol) - "Drug sensitivity analysis identified BX-795 and tozasertib as potential treatments for tumors with high IGSF8 expression. Knockdown of IGSF8 significantly inhibited the proliferation ability of prostate cancer cells. Our findings indicated that IGSF8 might be used as a potential prognostic marker and therapeutic target for various cancers."

Biomarker • Journal • Pan tumor • Acute Myelogenous Leukemia • Cervical Adenocarcinoma • Cervical Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer • Solid Tumor • CD276

Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer's mice model. (PubMed, Sci Rep) - "Pre-administration of LY294002, a PI3K/Akt pathway inhibitor, partially reversed the protective effects of Tozasertib, suggesting possible involvement of this pathway. However, as the mechanism was inferred primarily through pharmacological antagonism, further studies including direct molecular assessments (e.g. p-Akt/t-Akt) are warranted to confirm the role of FGF1/PI3K/Akt signaling in Tozasertib's action."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Pain • BAX • BCL2 • CASP3 • CAT • IL6 • TNFA

Deciphering lactate metabolism in colorectal cancer: Prognostic modeling, immune infiltration, and gene mutation insights. (PubMed, World J Gastroenterol) - "This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Baeyer-Villiger monooxygenase immobilized on magnetic nanoparticles: reusable biocatalytic system for drug metabolite synthesis. (PubMed, Int J Biol Macromol) - "Notably, BVMO@BION achieved over 95 % conversion efficiency for the N-oxidation of tozasertib (an anti-cancer drug) across nine reaction cycles (2 h each) over 3 days, while activity recovery values ranged from 81 % to 127 %. For S-oxidation of ethionamide (an antibiotic used in multidrug-resistant tuberculosis) approximately 26 % conversion was consistently achieved across eight 1-hour cycles. This work demonstrates that BVMO@BION is a robust, magnetically recoverable platform for repeated and selective drug metabolite synthesis, supporting greener and more efficient pharmaceutical development."

Journal • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Chemokine-like factor-like MARVEL transmembrane domain-containing 1 identified as a novel target protein for immune dysregulation in sepsis: A machine learning and molecular dynamics framework for diagnostic biomarkers and therapeutic exploration. (PubMed, Int J Biol Macromol) - "This study identified key immune biomarkers for sepsis, developed a highly accurate prediction model, and revealed promising therapeutic compounds. Notably, this is the first study to link CMTM1 to sepsis. These findings offer novel perspectives on accurate diagnosis and targeted therapy of immune dysregulation in sepsis."

Biomarker • Journal • Immunology • Infectious Disease • Inflammation • Septic Shock • Systemic Inflammatory Response Syndrome • JAK2 • MAPK14 • S100A6 • S100A8

Identification of Ion Channel-Associated Prognostic Biomarkers for Lung Adenocarcinoma. (PubMed, J Environ Pathol Toxicol Oncol) - "The drug prediction results showed that individuals with LUAD in the low-risk group were more sensitive to paclitaxel, BI 2536, pyrimethamine, and VX-680, while individuals with LUAD in the high-risk group to erlotinib, sorafenib, panitumumab, PHA-665752, and roscovitine. In summary, ion channel-related genes can provide valuable information for prognosis assessment and drug treatment of LUAD patients."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor