Telintra (ezatiostat) / MabVax - LARVOL DELTA

Single-cell transcriptomics of AL amyloidosis reveals pathogenic mechanisms, immune interactions and altered clonal and polyclonal plasma cell phenotypes (ASH 2025) - "Treating ALMC-1 cellline with the GSTP1 inhibitor ezatiostat reduced GSTP1 expression, triggered apoptosis (caspase cleavageand Annexin V staining), and significantly decreased cell viability in a dose-dependent way within 24hours... Our scRNA-seq study in AL amyloidosis delineates the transcriptomic landscape of mPCs,comparing them to nmPCs and hPCs. We identify novel therapeutic targets, including GSTP1, and revealthat even the polyclonal plasma cells in AL patients exhibit an altered phenotype. Additionally, weuncover immune communication pathways that may drive disease progression."

IO biomarker • Amyloidosis • Hematological Malignancies • Multiple Myeloma • ANXA5 • DKK1 • DNAJB1 • DUSP2 • GSTP1 • HSPA1A • HSPA6 • ITGB2 • ITM2A • ITM2B • MIF • MZB1 • NOTCH2 • PSMB8 • PSMB9 • SDC1 • TGFB1 • XBP1

PERTURBATIONS OF ANTIOXIDANT METABOLISM REVEAL REDOX-REGULATED PATHWAYS ESTABLISHING SURVIVAL REQUIREMENTS AND VULNERABILITIES OF AML (EHA 2025) - "To evaluate the effect of different compounds perturbing cellular antioxidant system (buthionine sulfoximine, auranofin, ezatiostat and ML-210) on the proliferation of leukemic cells we used multiple AML cell lines (ML-2, NOMO-1, SHI-1, Monomac-6 and OCI-M2 cells) and real-time monitored their proliferation using live-cell imaging methods. Collectively, we determined the nodes of the leukemia antioxidant system that are critical for cell survival and identified changes in protein abundance and oxidation state triggered by their perturbation. Targeting such proteins and their pathways may represent an efficient strategy to improve the therapeutical outcomes of AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • GPX4 • GSTP1

GSTP1 inhibits angiotensin II-induced atrial fibrillation by regulating ferroptosis. (PubMed, Europace) - "We investigated the role of GSTP1 in atrial remodeling and NRAMs by the ferroptosis inhibitor Ferrostatin-1 (Fer-1), AAV9-cTNT-GSTP1 and GSTP1 inhibitor Ezatiostat...Overexpression of GSTP1 inhibited Ang II-induced myocardial injury, oxidative stress, and ferroptosis in vitro. Therefore, these results preliminarily demonstrate that GSTP1-mediated ferroptosis plays a crucial role in the Ang II-induced atrial fibrillation model and can be considered a potential therapeutic target for atrial fibrillation."

Journal • Atrial Fibrillation • Cardiovascular • GSTP1

Upregulation of GSTP1 mediated by chimeric TFE3 promotes TFE3-tRCC progression by targeting JNK signaling pathway. (PubMed, World J Surg Oncol) - "Upregulation of GSTP1 mediated by chimeric TFE3 promotes TFE3-tRCC progression by targeting JNK signaling pathway, which underscore the potential of GSTP1 as a promising therapeutic target for TFE3-tRCC."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ANXA5 • GSTP1 • TFE3

Galangin alleviated Doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through GSTP1/JNK pathway. (PubMed, Phytomedicine) - "Gal could inhibit ferroptosis and protect against DIC through regulating the GSTP1/JNK pathway. Our research has identified a novel pathway through which Gal regulates DIC, providing valuable insights into the potential therapeutic efficacy of Gal in mitigating cardiotoxic effects."

Journal • Cardiovascular • Fibrosis • Immunology • Oncology • GPX4 • GSTP1 • MAPK8 • PACERR • PTGS2 • SLC7A11

Upregulation of Glutathione S Transferase P in Lung Epithelial Cells Augmentsinterleukin 1 Beta (IL1B)-induced Pro-inflammatory Signaling in Association With Oxidation of Ovarian Tumor Deubiquitinase 1 (OTUB1); Implications of Aberrant Epithelial Cells in Pulmonary Fibrosis (ATS 2024) - "Mouse tracheal basal cells (MTB) were stimulated with IL1B and subjected to incubation with the GSTP or System XC- inhibitors, TLK199 or erastin, respectively. These findings demonstrate that GSTP-linked PSSG is linked to the aberrant epithelial cell population in IPF and that OTUB1 is a PSSG target. These findings along with the prior demonstration that absence of Otub1 impairs lung alveologenesis (PMID: 34793600) point to OTUB1-SSG as a regulatory mechanism of epithelial plasticity."

Fibrosis • Immunology • Oncology • Ovarian Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Targeted Protein Degradation • CCL20 • CLDN4 • CXCL1 • GLRX • GSTP1 • IL1B • SLC7A11 • TSLP

Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors. (PubMed, Adv Sci (Weinh)) - "Using patient-derived organoids from an ALK-translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long-term control of LUAD through targeting CSCs."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAMK2A • GSTP1

Glutathione Regulates Endothelial Cell Function And Vegfr2 Signaling (ATVB-PVD-GPM 2022) - "Combined these data suggest Src mediates the 2-AAPA + H 2 O 2 activation of VEGFR2. Glutathione S-transferase P1 (GSTP1) catalyzes the enzymatic glutathionylation of proteins, The GSTP1 inhibitor TLK199 (50 µM) abrogated the effects of 2-AAPA + H 2 O 2 on VEGFR2 and experiments are underway to determine the glutathionylation status of Src in our system and its effect on the interaction of Src and VEGFR2."

Oncology • GSTP1

Glutathione Regulates Endothelial Cell Function and VEGFR2 Signaling. (PubMed, FASEB J) - "Combined these data suggest Src mediates the 2-AAPA + H O activation of VEGFR2. And that glutathionylation is necessary for this effect, co-immunoprecipitation experiments are underway to determine the glutathionylation status of Src in our system and its effect on the interaction of Src and VEGFR2."

Journal • Oncology • GSTP1

Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2. (PubMed, Redox Biol) - "GSTP contributes to the pathogenesis of allergic airways disease in association with enhanced glycolysis and oxidative disruption of PKM2. Our findings also suggest a PKM2-GSTP-glycolysis signature in asthma that is associated with severe disease."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL1B • PKM

Deactivation of the JNK Pathway by GSTP1 Is Essential to Maintain Sperm Functionality. (PubMed, Front Cell Dev Biol) - "No effects in intracellular calcium levels and acrosome membrane integrity were observed. In conclusion, the present work has demonstrated, for the first time, the essential role of GSTP1 in deactivating JNK, which is crucial to maintain sperm function and has also set the grounds to understand the relevance of the GSTP1-JNK heterocomplex for the regulation of mammalian sperm physiology."

Journal • Immunology • Infertility • GSTP1 • MAPK8

GSTP1 knockdown and inhibition impairs pancreatic ductal adenocarcinoma (PDAC) growth (AACR 2018) - "...Intrigued by these results, we next examined whether pharmacological inhibition with a selective GSTP1 inhibitor, Ezatiostat (TLK199), also impaired PDAC pathogenicity...Moreover, GSTP1 knockdown results in elevated ROS levels and an extended G0/G1 phase of the cell cycle. With these data, we propose that GSTP1 is a novel therapeutic target for PDAC."

IO Biomarker • Non Small Cell Lung Cancer • Pancreatic Cancer

Development of Telintra as an Inhibitor of Glutathione S-Transferase P. (PubMed, Handb Exp Pharmacol) - "It has diverse cellular functions that include, thiolase activities with small electrophilic agents or susceptible cysteine residues on the protein to mediate S-glutathionylation, and chaperone binding with select protein kinases. Preclinical and clinical testing of a nanomolar inhibitor of GSTP, TLK199 (Telintra; Ezatiostat) has indicated a role for the enzyme in hematopoiesis and utility for the drug in the treatment of patients with myelodysplastic syndrome."

Journal • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Respiratory Diseases

Phase 2 study of Telintra in myelodysplastic syndrome (clinicaltrials.gov) - P2, N=130; Not yet recruiting → Recruiting

Enrollment open • Hematological Malignancies

Study of (Telintra) in non-del(5q) myelodysplastic syndrome (clinicaltrials.gov) - P2, N=162; Not yet recruiting; New P2 trial

New trial • Hematological Malignancies

Phase 1 dose-ranging study of oral ezatiostat hydrochloride (Telintra, TLK199) in combination with lenalidomide (Revlimid) in patients with non-deletion(5Q) low to intermediate-1 risk myelodysplastic syndrome (MDS) (ASH 2011) - Presentation Time: Sunday, December 11, 2011, 6:00 PM-8:00 PM; P1, N=18; TLK199.1104; Three of 8 (38%) RBC transfusion-dependent evaluable pts achieved transfusion independence including 1 responder who did not respond to prior lenalidomide; In responders, the median increase in hemoglobin level was 3.4g/dL (from 7.9g/dL); In 2 of 4 thrombocytopenic pts, a HI-platelet (HI-P) response was observed; A bilineage (HI-E and HI-P) response in 2 of 4 pts with anemia and thrombocytopenia was reported

P1 data • Hematological Malignancies

A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome (Cancer) - P2, N=89; 40% HI-E rate was observed in pts who had prior lenalidomide and no prior hypomethylating agents (HMAs), 45% of pts achieved significant RBC transfusion reduction and 27% of pts achieved transfusion independence; 28% HI-E rate was observed in pts who were both lenalidomide and HMA naive, with 4 of 8 (50%) pts achieving clinically significant RBC transfusion reductions

P2 data • Hematological Malignancies

Contributions of enzymes and gut microbes to biotransformation of perfluorooctane sulfonamide in earthworms (Eisenia fetida). (PubMed, Chemosphere) - "In addition, both 1-Aminobenzotriazole (ABT) and ezatiostat hydrochloride (TLK199), which were selected to inhibit the CYP and GST enzymes, respectively, demonstrated inhibition effects on biotransformation of FOSA in earthworms with a dose-dependent relationship. However, the concentrations of FOSA weren't changed by the bacteria isolated from worm gut, suggesting that gut bacteria did not contribute to FOSA biotransformation in earthworms. The results of this study confirm that the transformation of FOSA in earthworms is mediated mainly by enzymes rather than by gut microbes."

Journal

Study of Telintra for Treatment of Chemotherapy Induced Neutropenia in Patients With Non‑Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=1; Terminated; Sponsor: Telik; Withdrawn ➔ Terminated; Study TLK199.2102 was terminated for lack of enrollment.

Clinical • Trial termination

Study of Telintra for Treatment of Chemotherapy Induced Neutropenia in Patients With Non‑Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=1; Terminated; Sponsor: Telik; Initiation date: May 2008 ➔ Oct 2008

Clinical • Trial initiation date

Study of Telintra for Treatment of Chemotherapy Induced Neutropenia in Patients With Non‑Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=1; Terminated; Sponsor: Telik; N=135 ➔ 1

Clinical • Enrollment change

GSTP mediated S-glutathionylation of GRP78 attributes to multiple myeloma resistance (AACR 2019) - "The proteasome inhibitor bortezomib (Btz) is used in the treatment of multiple myeloma (MM), but its efficacy is restricted by the wide-spread occurrence of resistance. Moreover, inhibition of GSTP with Telintra restored Btz sensitivity, decreased S-glutathionylation and increased expression of markers of UPR induced apoptosis. We conclude that altered GSTP expression and S-glutathionylation of key ER-localized proteins are significant contributors to drug response and resistance in MM treated with Btz."