thioguanine / Generic mfg. - LARVOL DELTA

Very severe intrahepatic cholestasis of pregnancy contributed to by azathioprine dosing. (PubMed, BMJ Case Rep) - "Thiopurine metabolites ratio, 6-methylmercaptopurine: 6-thioguanine nucleotide (6MMP:TGN) was 34 at 12/40 and 21 at 27/40. A multidisciplinary plan was made in conjunction with the patient for delivery between 35 and 36 weeks. This case highlights the risks of thiopurine use in pregnancy and supports ceasing azathioprine treatment immediately at the onset of ICP, avoiding TSBA levels rising."

Journal • Cholestasis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Gynecology • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Obstetrics • Pruritus

Investigating the evolutionary history of the biosynthetic gene cluster for the cytotoxic purine analog, 6-thioguanine. (PubMed, Mol Genet Genomics) - "In some lineages, the cluster has been lost, while in others it has been acquired horizontally from distantly related groups. Maintenance of the cluster across diverse bacterial species suggests multiple roles for 6-thioguanine in the general ecology of these species."

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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update. (PubMed, Clin Pharmacol Ther) - "Genetic variants in these genes are present in all world populations; however, their frequency varies by ancestry. In this updated guideline, we provide recommendations for adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genotypes, including for individuals with variants in both genes (updates on www.clinpgx.org)."

Biomarker • Journal • NUDT15

Development and Application of an LC-MS/MS Method for Simultaneous Quantification of Azathioprine and Its Metabolites: Pharmacokinetic and Microbial Metabolism Study of a Colon-Targeted Nanoparticle. (PubMed, Pharmaceuticals (Basel)) - " AZA, 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanine (6-TG) were quantified in positive ion mode, and 6-thiouric acid (6-TU) in negative ion mode. This method provides accurate and precise quantification of physiologically relevant concentrations of AZA and its metabolites (6-MP, 6-MMP, 6-TG, and 6-TU), offering a bioanalytical tool for the pharmacokinetic and gut microbiota metabolism studies of AZA formulations. These findings suggest that APZE is a promising drug delivery formulation."

Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Harnessing Purines: Anticancer Activity and Target-Specific Approaches. (PubMed, Med Chem) - "For the anti-cancer drugs, Purine-based compounds remain a versatile and evolving class. Their targeted design offers promising avenues for personalized cancer therapy, warranting further clinical exploration."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

TEMPLE: Thiopurine Enhanced Mutations for PD-1/Ligand-1 Efficacy (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: Kristoffer Rohrberg | Recruiting ➔ Completed | N=39 ➔ 18

Enrollment change • IO biomarker • Trial completion • Tumor mutational burden • Hepatocellular Cancer • Oncology • Solid Tumor • TMB

Development and Validation of a Sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Simultaneous Quantification of Thiopurine Nucleotides in Human Red Blood Cells. (PubMed, Cureus) - "The objectives of the current study were to validate and develop a highly repeatable and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and 6-methylmercaptopurine (6-MMP) within human red cells. Conclusions The developed LC-MS/MS approach gives a reliable technique for the simultaneous quantification of thiopurine metabolites within erythrocytes. With its reliability and sensitivity, it makes a suitable approach for therapeutic drug monitoring at the clinical level, therefore contributing toward enhanced thiopurine therapy under the banner of personalized medicine."

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In silico identification of deleterious NT5C2 and PRPS1 mutations driving thiopurine resistance in relapsed acute lymphoblastic leukemia. (PubMed, Cancer Genet) - "Protein-protein interaction networks indicate that these variations are involved in nucleotide metabolism and pharmacological responses, confirming their role in thiopurine resistance. In summary, NT5C2 and PRPS1 gene variations may act as potential biomarkers for resistance and hence require more experimental validation of VUS to determine their significance."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • NT5C2 • PRPS1

A nitrogen-rich Eu-MOF for ultrasensitive fluorescence detection of 6-mercaptopurine and 6-thioguanine. (PubMed, Talanta) - "Density functional theory calculations further investigated the synergistic effect between the inner filter effect and host-guest interactions underlying the detection mechanism, as well as the electron transfer behavior of Eu2-tbia during the fluorescent sensing process. This work not only establishes Eu2-tbia as a robust sensing platform for monitoring purine analogs in biomedical and environmental applications but also provides fundamental insights into the structure-property relationships of MOF-based sensors."

Journal • Oncology

AALL2331: Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL) (clinicaltrials.gov) - P2/3 | N=1708 | Not yet recruiting | Sponsor: Children's Oncology Group | Initiation date: Mar 2026 ➔ Jun 2026

Trial initiation date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Squaramide-Based MOF Enables Hydrogen-Bond-Directed Ultraselective Guanine Detection and Drug Monitoring. (PubMed, Inorg Chem) - "Significantly, Co-DBDP represents a pioneering approach for fluorescence enhancement-based detection of G-based pharmaceuticals acyclovir (ACV) and 6-thioguanine (6-TG), while also successfully quantifying nucleotides (GMP/GDP/GTP). This demonstrates unparalleled diagnostic versatility. The paradigm of hydrogen-bond-mediated confinement offers a generalized design strategy for developing modular sensing platforms aimed at disease-relevant biomarkers."

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EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients. (PubMed, Commun Biol) - "High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing."

Journal • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • PTEN • TP53

Exploring the Therapeutic Potential of Ferroptosis in Gastric Cancer. (PubMed, Cancer Manag Res) - "It also summarizes other drugs such as 6-Thioguanine, Polymerase theta, levobupivacaine and clinical application drugs, which target ferroptosis, the effect of them in treating GC. This review highlights the potential of ferroptosis induction in GC treatment, providing new avenues for clinical intervention. Finally, this review looks forward to the translational prospects of targeting ferroptosis in the development of GC treatment, offering key insights for future research directions and therapeutic strategies."

Journal • Review • Gastric Cancer • Oncology • Solid Tumor

Thiopurine pharmacogenomic landscape in India: TPMT and NUDT15 allele frequencies (ASH 2025) - "Thiopurines—such as azathioprine, mercaptopurine, and thioguanine—are commonly used in hematology as immunosuppressants and chemotherapeutic agents. We also identified rare, potentially deleterious TPMT variants that are absent or underrepresented in global reference datasets, underscoring the value of population-specific pharmacogenomic profiling. Our findings support pre-treatment NUDT15 genotyping (and TPMT where indicated) with genotype-informed dose adjustment and early monitoring to reduce myelosuppression-related treatment interruptions."

Biomarker • NUDT15

Effect and mechanism of allopurinol in ALL maintenance therapy: Reducing hepatotoxicity and improving myelosuppression effect via TPMT inhibition and increased DNA-thioguanine levels (ASH 2025) - "Introduction: 6-Mercaptopurine (6-MP) based-maintenance therapy is essential to cure acute lymphoblastic leukemia (ALL). In conclusion, intensifying 6-MP dosing does not achieve adequate myelosuppression effect, but primarily increases the risk of hepatotoxicity by experiencing skewed metabolism. Low-dose 6-MP combined with allopurinol, rather than intensifying 6-MP dose, could be an alternative strategy for better efficacy and lower risk of hepatotoxicity."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Hepatology • Leukemia • NUDT15

Identifying patients with indolent Acute Myeloid Leukemia: Long term survivors after best supportive care only, results from the pethema registry (ASH 2025) - P=N/A | "BSCincluded transfusions and other supportive measures, with or without oral cytoreductive agents (e.g.,hydroxyurea, melphalan, mercaptopurine or thioguanine). Approximately 8% of elderly AML patients treated exclusively with BSC show unexpectedly long survival,consistent with an indolent clinical course, reflecting that in the absence of more efficacious therapeuticregimens, some patients could benefit from less invasive approaches. Easily measurable clinicalparameters such as bone marrow blasts, platelet count, and serum albumin may help identify thesepatients. Further prospective and molecular studies are warranted to validate these findings andelucidate the biological underpinnings of iAML."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • NPM1

Thioguanine and decitabine can overcome hypomethylating agent resistance in patients with advanced myeloid malignancies (ASH 2025) - "Background : Despite active therapies such as hypomethylating agents (HMA) and venetoclax advancedmyeloid malignancies, outcomes in relapsed/refractory (R/R) disease or secondary acute myeloidleukemia (AML) remain poor. 6TG/DEC is a clinically active regimen in high-risk and R/R AML with a 30% ORR andfavorable survival outcomes compared to historical controls. Single-cell proteomic data reveal immune-modulatory mechanisms that may underlie therapeutic response, offering a novel lens into resistancebiology. Taken together, this combination remains a viable therapeutic option for elderly and unfitpatients with high-risk and R/R AML who cannot tolerate intensive chemotherapy."

Clinical • Metastases • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • B2M • CD36 • SCARB1

Impact of noncoding tandem repeat sequence on TPMT function and thiopurine metabolism in children with ALL (ASH 2025) - "Of these, 369 cases also had 6-MP metabolites quantified using liquid chromatography-mass spectrometry, including for thioguanine nucleotides (TGNs) and methylmercaptopurine nucleotides(MMPNs)...Studying whole genome sequencing in large reference populations and ALL patients, we havedemonstrated that the TPMT-VNTR impacts TPMT transcription and enzymatic function in addition tocoding variants in this gene. This work highlights the importance of noncoding variants in modulatingdrug efficacy and toxicity in hematological malignancies."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • TPMT

A semi-focused multi-state variant of the mapping approach to surface hopping. (PubMed, J Chem Phys) - "A key distinguishing aspect of our approach is that only a selected subset of electronic states, identified through an appropriate clustering procedure, is initially populated. Test simulations of the ultrafast photodynamics of three molecular systems (spiropyran, thioguanine, and azobenzene) show that SMASH gives results closely matching those of decoherence-corrected fewest-switches surface hopping, while eliminating the need for the ad hoc decoherence correction."

Journal • Metabolic Dysfunction-Associated Steatohepatitis

Development and Validation of a Sensitive LC-MS/MS Method for Determination of Deoxythioguanosine in Human DNA and its Application in Thiopurine-Treated Inflammatory Bowel Disease Patients. (PubMed, J Chromatogr Sci) - "Nucleoside diphosphate-linked moiety X-type motif 15 variant carriers (*2, *3, *5, *6) showed significantly higher DNA-TG/dose and DNA-TG/erythrocyte thioguanine nucleotides ratios than wild-type patients (P = 0.0023, P = 0.0001). In summary, this method was simple and stable to detect dTG in DNA, which may act as a promising biomarker predicting the toxicity and efficacy in patients treated with thiopurine."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • NUDT15

Allopurinol increases DNA-thioguanine nucleotides during maintenance therapy in pediatric acute lymphoblastic leukemia. (PubMed, Haematologica) - "Not available."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

An optimized LC-ESI-MS/MS assay for erythrocyte 6-TG and 6-MMPD: Addressing critical methodological considerations for thiopurine metabolite monitoring. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The erythrocyte-based active metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotides (6-MMPN) serve as biomarkers reflecting systemic drug exposure and predicting both therapeutic efficacy and adverse reactions...Selectivity, carry-over, intra- and inter-batch accuracy and precision, reproducibility, recovery, matrix effect, and stability all complied with the acceptance criteria outlined in the US Food and Drug Administration (FDA) Bioanalytical Method Validation Guidance (2018). The validated method was successfully employed to quantify 6-TG and 6-MMPD in samples obtained from 20 patients with IBD or ALL."

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

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between TPMT/NUDT15 and thiopurines. (PubMed, Eur J Hum Genet) - "The current guideline describes the gene-drug interactions for TPMT, NUDT15 and thiopurines (azathioprine, 6-mercaptopurine and thioguanine). For TPMT or NUDT15 IM treated for leukaemia, starting with the normal dose can be considered and then decrease the dose to the advised dose described above in case toxicities occur. For NUDT15 PM reduced starting dose is advised only if an alternative is not possible, due to a higher uncertainty in the calculated dose reduction for NUDT15 PM than for TPMT PM.DPWG classifies genotyping for TPMT and NUDT15 "essential" before thiopurine initiation."

Biomarker • Journal • CNS Disorders • Depression • Hematological Malignancies • Leukemia • Oncology • Psychiatry • NUDT15

Direct evidence of singlet molecular oxygen [O2 (1Δg)] production from UVA excited 6-thioguanine. (PubMed, Photochem Photobiol) - "These compounds presented kt values of 1.5 × 107 L mol-1 s-1 and 1.1 × 107 L mol-1 s-1, respectively. Through the comparison of these values with the ones obtained for 2'-deoxyguanosine (dGuo) and its oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), we aim to provide new insights into the 6-TGua-containing DNA (DNA-6-TGua) reactivity towards 1O2 in a biological context."

Journal • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

LC-MS/MS quantification of 6-methylthio-2'-deoxyguanosine and 6-thio-2'-deoxyguanosine in genomic DNA with enzymatically synthesized isotope-labelled internal standards. (PubMed, Anal Bioanal Chem) - "The thiopurines 6-mercaptopurine and 6-thioguanine (TG) are analogs of guanine and are used in the treatment of hematological malignancies and immune-mediated inflammatory diseases. dMeTG could also be detected in patient samples, although in low amounts and primarily in samples with high DNA-TG levels. The developed method for the quantitation of dMeTG and dTG can be used in further studies to investigate the role of DNA-MeTG in the mechanism of action of thiopurines, including its antileukemic efficacy and effects on acquired mutations."

Journal • Tumor mutational burden • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • TMB