thioguanine / Generic mfg. - LARVOL DELTA

Purine and pyrimidine analogs differentially regulate cell wall precursor biosynthesis to control β-lactam susceptibility in methicillin-resistant Staphylococcus aureus. (PubMed, mBio) - "We previously showed that the pyrimidine analogs 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUrd) synergize with β-lactams...Gemcitabine (Gem) and mitomycin C (Mito), such as 5-FU and 5-FUrd, exhibited intrinsic anti-MRSA activity and potentiated β-lactams, whereas the purine analog 6-thioguanine (6-TG) showed distinct, often antagonistic effects...Consistent with this, pyrimidine analogs also suppressed GlmS expression, potentially limiting UDP-GlcNAc production required for cell wall synthesis, and synergized with fosfomycin...Additionally, glutathione-mediated attenuation of killing implicated reactive oxygen species in the bactericidal activity of cloxacillin combinations. Finally, these agents displayed strong antibiofilm activity, further enhanced in combination with daptomycin and rifampicin...These drugs altered the bacterial cell wall and other metabolic pathways linked to antibiotic susceptibility. Our findings reveal the potential to repurpose certain..."

Journal • Infectious Disease • Oncology

Risk of Incident Melanoma With TNF-Alpha Inhibitor Therapy in Inflammatory Bowel Disease: A Propensity-Matched Cohort Study (ACG 2026) - " Using the TriNetX U.S. Collaborative Network, we identified adults â¥18 years with IBD who initiated TNFi on or before February 7, 2024; controls initiated mesalamine or a non-TNFi biologic (ustekinumab, vedolizumab, risankizumab, mirikizumab, or guselkumab). Patients with prior melanoma or melanoma in situ; exposure to opposite-class advanced therapy, JAK inhibitors (tofacitinib, upadacitinib), thiopurines (azathioprine, mercaptopurine, thioguanine), or methotrexate before or within 5 years after index were excluded... In TNFi vs mesalamine, 21,848 matched pairs (mean age 38.9 ± 17.9 years; 51.1% female sex; 78.0% White) accrued mean follow-up of 2.5 years (median 3.0 years). There was no statistically significant difference in incident melanoma (0.10% vs 0.08%; OR 1.22, 95% CI 0.66â2.28; P=0.53) or composite outcome (0.11% each; OR 1.04, 0.59â1.82; P=0.89). Melanoma in situ alone was not separately reportable in this comparison due to small..."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Melanoma • Solid Tumor

Porto-sinusoidal vascular disorder and sinusoidal obstructive syndrome in patients treated with thiopurines: a systematic review. (PubMed, Ann Hepatol) - "Thiopurines can precipitate a spectrum of hepatic microvascular injury. Evidence most strongly implicates 6-TG (dose/exposure dependent), whereas AZA/6-MP-associated PSVD and related vascular lesions is less consistent but remains clinically relevant. In exposed patients, new thrombocytopenia or splenomegaly should trigger evaluation for portal hypertension; thiopurine withdrawal is recommended when PSVD/SOS is suspected."

Journal • Acute Lymphocytic Leukemia • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Inflammation • Inflammatory Bowel Disease • Leukemia • Liver Failure • Oncology • Otorhinolaryngology • Pediatrics • Portal Hypertension • Rheumatology • Thrombocytopenia • Thrombosis • Transplantation

AALL1631: Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=352 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial primary completion date: Sep 2027 ➔ Jun 2026

Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • CSF1R • PDGFRA • PDGFRB

A Phase 1b/2 Study of Atezolizumab in Combination with Thiopurine Therapy in Patients with Metastatic Solid Tumors and Intermediate Tumor Mutational Burden. (PubMed, Cancer Res Commun) - "A safe and tolerable dose of 6-mercaptopurine and 6-thioguanine combined with atezolizumab was identified in patients with metastatic solid tumors. Although clinical benefit was limited, the TEMPLE study informs future investigations in patients with less advanced disease."

Journal • P1/2 data • Tumor mutational burden • Anorexia • Fatigue • Oncology • Solid Tumor • TMB

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=280 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

Development and Validation of Simultaneous Quantification of 6TGN and 6MMPN in Whole Blood Using LC-MS/MS: An Application to Therapeutic Drug Monitoring in Hematological Malignancies and in Inflammatory Bowel Diseases. (PubMed, Biomed Chromatogr) - "Therapeutic drug monitoring (TDM) of its DNA-incorporated metabolites 6-thioguanine nucleotides (6TGN) and 6-methylmercaptopurine nucleotides (6MMPN) is of high interest to optimize efficacy and prevent toxicity...The method was applied to 749 clinical samples from patients with acute lymphoblastic leukemia or chronic inflammatory diseases. A sensitive and simple LC-MS/MS method was validated for 6TGN and 6MMPN in whole blood and was successfully applied to clinical samples for TDM."

Journal • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Leukemia • Oncology

A QM/MM study on triplet decay of 6-thioguanine and 6-selenoguanine with explicit solvent. (PubMed, J Mol Model) - "Spin-orbit coupling (SOC) matrix elements were calculated using the PySOC program based on the Breit-Pauli spin-orbit Hamiltonian with the effective charge approximation. Nonradiative ISC rates were estimated using a quasi-Marcus approach, and noncovalent interactions were analyzed using QTAIM and IGMH methods with Multiwfn."

Journal

Nuclear PI3P produced by the Beclin-1/Vps34 complex regulates DNA mismatch repair. (PubMed, Nucleic Acids Res) - "Functionally, loss of nuclear PI3P blunts MMR-dependent DNA damage signaling and confers 6-thioguanine resistance in cultured cells and in Beclin-1-deficient zebrafish in vivo. These findings reveal an autophagy-independent nuclear function for the Beclin-1/Vps34 complex in genome maintenance and identify PI3P as a lipid mediator of MMR, thereby expanding the functional repertoire of nuclear phosphoinositide signaling."

Journal • Mismatch repair • BECN1 • MSH2 • MSH3 • MSH6 • MSI

A smartphone-based, calibration-free Nafion-modified SPCE electrochemical sensor for clinical validation of 6-thioguanine in erythrocyte lysate and serum. (PubMed, Biosens Bioelectron) - "The immunosuppressive prodrugs azathioprine and 6-mercaptopurine necessitate therapeutic drug monitoring of their active metabolite, 6-thioguanine (6-TG), due to their narrow therapeutic window and substantial risk of severe adverse effects. Clinical validation using 50 patient samples demonstrates strong agreement with high-performance liquid chromatography results, and the US method yields outcomes statistically equivalent to those obtained via the standard addition approach. By resolving the redox mechanism and translating this insight into a calibration-free POC sensor, this work offers a clinically deployable solution for personalized thiopurine therapy."

Journal

Use of azathioprine and allopurinol combination therapy to optimise outcomes in autoimmune hepatitis: a single centre experience (BSG 2026) - "AZA efficacy correlates with 6-thioguanine (6-TGN) levels > 220 pmol/8x10 8 RBC, while elevated 6-methylmercaptopurine nucleotides (6-MMPN) are linked to hepatotoxicity. We are now exploring the benefit of transitioning patients on AZA mono-therapy with low TGN levels to allopurinol co-therapy. View this table: View inline View popup Abstract P58 Table 1"

Clinical • Combination therapy • Autoimmune Hepatitis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease

Structural and Functional Disruption of Thiopurine S‑Methyltransferase by the A80P Variant: A Simulation and Genotyping Study. (PubMed, ACS Omega) - "Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. These findings support the importance of population-specific pharmacogenetic screening. Tailoring genetic tests to local variant frequencies can improve cost-effectiveness, reduce unnecessary testing, and contribute to safer, more personalized cancer therapy."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TPMT

Pharmacogenetics and Metabolite-Guided Optimization of Thiopurine Therapy in Taiwanese Inflammatory Bowel Disease (AOCC-IMKASID 2026) - "Background / Aim: Thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6-MP), remain key steroid-sparing and combination agents with anti-tumor necrosis factor therapy in inflammatory bowel diseases (IBD)...Among 125 thiopurine-treated IBD patients, serial 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) levels were measured using LC-MS/MS after dose stabilization... In Taiwanese IBD patients, NUDT15 R139C is the principal determinant of thiopurine dose requirement and leukopenia risk. Despite lower Asian weight-based dosing, marked interindividual variability persists. A precision strategy integrating NUDT15-guided initial dosing with ongoing therapeutic drug monitoring optimizes safety and efficacy in Asian populations."

Biomarker • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Leukopenia • CRP • ITPA • MTHFR • NUDT15

Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response. (PubMed, Nat Commun) - "These degraders, in conjunction with orthogonal CRISPR knock-out and reconstitution experiments, support a non-enzymatic role for NUDT5 in modulating the cellular response to 6-TG. Depletion of NUDT5 protein is antagonistic to NUDT15 inhibition, suggesting a distinct mode-of-action with potential implications for patient therapy."

Journal • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • NUDT15 • NUDT5

REAL-WORLD IMPLEMENTATION OF TPMT TESTING AND METABOLITE-GUIDED THIOPURINE THERAPY IN PAEDIATRIC INFLAMMATORY BOWEL DISEASE: A CONTEMPORARY SINGLE-CENTRE ANALYSIS (ESPGHAN 2026) - "We extracted TPMT activity, genotyping, serial 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) measurements, dose adjustments, and adverse events...One hundred received thiopurines: azathioprine (n=81, median 1.5 mg/kg/day) and 6-mercaptopurine (n=19, median 1.0 mg/kg/day)...Findings support integrated pharmacogenetic and metabolite-guided thiopurine therapy in paediatric IBD. Contact e-mail address [email protected]"

Clinical • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Neutropenia • Pancreatitis • Pediatrics

A double-edged sword: life-threatening adverse effects of the Thiopurine drugs Azathioprine and 6-Mercaptopurine (6-mp) (BAD 2026) - "In 2022, 6-MP was commenced and later combined with dupilumab in 2023, followed by subsequent therapeutic trials with tralokinumab and lebrikizumab...Levels of 6-thioguanine nucleotide (6-TGN) were monitored regularly and remained within the therapeutic range throughout this period...Subsequently, the patient developed acute renal failure requiring haemodialysis and was diagnosed with microangiopathic haemolytic anaemia and atypical haemolytic uraemic syndrome, for which treatment with eculizumab was initiated. This case highlights the potential for severe, multisystem thiopurine toxicity even in patients with normal TPMT and NUDT15 activity, requiring heightened clinical vigilance and monitoring."

Adverse events • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Contact Dermatitis • Dermatitis • Hematological Disorders • Immunology • Infectious Disease • Renal Disease • Septic Shock • NUDT15

The association between 6-thioguanine nucleotide levels, adalimumab exposure, immune response, and drug clearance. (PubMed, Crohns Colitis 360) - "Thiopurines are associated with improved infliximab pharmacokinetics (PK), but their impact on adalimumab PK and immunogenicity is not well defined. Higher 6-TGN levels are associated with reduced immunogenicity, higher adalimumab drug levels, and lower clearance. Thiopurine may enhance adalimumab PK and support a more favorable therapeutic response."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Modulation of Triplet-State Reactivity and Enhanced Singlet Oxygen Generation in Tricyclic Thiopurine Analogues. (PubMed, Int J Mol Sci) - "Thiopurines are efficient triplet-state photosensitisers; however, the practical application of canonical derivatives such as 6-thioguanine (6TG) and 6-thioguanosine (6TGuo) is limited by competing deactivation pathways that reduce the fraction of triplet states available for productive interaction with molecular oxygen...Analysis of triplet-state deactivation pathways showed that the enhanced photosensitising efficiency does not result from increased triplet formation, but from more effective use of the triplet-state population for energy transfer to molecular oxygen leading to singlet oxygen formation. These findings demonstrate that structural modification of the thiopurine scaffold enables control over triplet-state reactivity and provides a strategy for designing improved thiopurine-based photosensitisers for photodynamic therapy applications (PDT)."

Journal

SINGLE‑CELL SURFACE PROTEOMICS AND LONG‑READ METHYLOMICS IDENTIFY DETERMINANTS OF HMA RESPONSE AND RESISTANCE IN RELAPSED AML (EHA 2026) - "In a phase I trial of decitabine plus thioguanine (6TG), we observed a 30% response rate in R/R AML. (A) PNA workflow: Fixed cells are labeled with DNA-barcoded antibodies; proximity ligation converts nanoscale protein co-localization into sequenced DNA relationships for network reconstruction. (B) Differential CD34+ cell proximity landscape: Bubble plots show rewiring of surface protein neighborhoods between disease (1) and normal (2) states, highlighting network-level changes."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • CD36 • SCARB1

APOPTOTIC PRIMING DEFINES EFFECTIVE COMBINATION STRATEGIES WITH THIOGUANINE IN AML (EHA 2026) - "Results Synergistic interactions with 6-Tg were predominantly observed with apoptosis-modulating agents, including BH3 mimetics (e.g., the BCL-2 inhibitor venetoclax and the BCL-XL inhibitor A-1155463), PARP inhibitors, and HDAC inhibitors. In contrast, other cytotoxic and antimetabolite agents, including cytarabine, demonstrated limited or antagonistic interactions...Our data suggest a mechanistic rational linking 6-Tg metabolic activation, DNA incorporation, and mismatch repair- dependent stress to intrinsic mitochondrial apoptosis. This create a therapeutically exploitable primed state that can be leveraged through rational combination strategies."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • APAF1 • BCL2L1 • CASP3 • CASP9 • HPRT1 • MSH2 • MSH6

Severe Thiopurine-Induced Myelosuppression in a Pediatric Acute Lymphoblastic Leukemia Patient With the NUDT15 *1/*6 Genotype: A Brief Report. (PubMed, Clin Transl Sci) - "After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia...In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Febrile Neutropenia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombocytopenia • NUDT15

Testing Blinatumomab With or Without Revumenib in Patients With B-cell Acute Lymphoblastic Leukemia With a Genetic Change Requiring More Treatment (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: SWOG Cancer Research Network

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD19 • KMT2A

Increased risk of intrahepatic cholestasis of pregnancy in SLE women exposed to azathioprine (EULAR 2026) - "At the Montreal site, thiopurine metabolites [i.e. erythrocyte-free 6-thioguanine (6-TG), and 6-methylmercaptopurine (6-MMP)] were measured at each visit, with shunting defined using established cut-offs (i.e. 6-MMP/6-TG ratio ≥20 with 6-MMP >5700 pmol/8×10⁸ RBC).[3] Results Of 127 SLE pregnancies, 46 were AZA-exposed and 81 unexposed (Table 1). Thiopurine shunting in the second trimester appears to be a strong predictor of ICP. These findings underscore the need for metabolite monitoring and heightened vigilance when prescribing AZA in SLE pregnancies."

Clinical • Cholestasis • Hepatology • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

6-Mercaptopurine metabolic profiles and clinical outcomes in TPMT and NUDT15 phenotypes during maintenance therapy for Thai paediatric acute lymphoblastic leukaemia. (PubMed, Br J Clin Pharmacol) - "The TPMT and NUDT15 genes influence the side effects of 6-MP medications. Patients who have variations in both genes are at a higher risk of experiencing toxicity. High levels of 6-TGN are associated with TPMT variants, whereas low levels are linked to NUDT15 variants. This could facilitate more precise monitoring of toxicity."

Clinical data • Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • NUDT15

Early thiopurine metabolite monitoring in autoimmune hepatitis improves biochemical response at 6 months and enables early steroid withdrawal in a prospectively managed cohort (EASL 2026) - "Background and aims: In autoimmune hepatitis (AIH), only 25-55% of patients achieve transaminase normalization after 6 months of standard therapy with azathioprine or mycophenolate mofetil, highlighting the need for improved strategies. We previously showed that, due to poor correlation between weight‑adjusted thiopurine doses and metabolite levels of 6‑thioguanine / 6‑methylmercaptopurine (6TGN/6MMP), therapeutic drug monitoring (TDM) improves response rates...Eight patients (11%) were switched to combination therapy with allopurinol due to shunting toward 6MMP, defined by a 6MMP:6TGN ratio >5... Dose adjustments based on early TDM significantly improved 6-month biochemical response and facilitated early steroid withdrawal, supporting individualized thiopurine dose optimization."

Clinical • Autoimmune Hepatitis • Fibrosis • Hepatology • Immunology • Inflammation