Delving into the Latest Updates on Thioguanine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine

+ [26]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaPhiladelphia chromosome positive chronic myelogenous leukemia

Inactive Indication-

Originator Organization

Aspen Pharmacare Holdings Ltd.

Active Organization

Waylis Therapeutics LLCShanghai Donghai Pharmaceutical Co., Ltd.

Inactive Organization

Only For Children Pharmaceuticals SA

Drug Highest PhaseApproved

First Approval Date

US (18 Jan 1966),

Acute Myeloid LeukemiaPhiladelphia chromosome positive chronic myelogenous leukemia

RegulationOrphan Drug (EU)

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Structure/Sequence

Molecular FormulaC5H5N5S

InChIKeyWYWHKKSPHMUBEB-UHFFFAOYSA-N

CAS Registry154-42-7

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

Start Date28 Feb 2025

Sponsor / Collaborator

National Cancer Institute

NCT06533748

/ RecruitingPhase 2IIT

SJALL23H: Combination Antigen-Directed Induction Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma

This is a Phase II clinical trial testing the use of two antigen-directed therapies, inotuzumab and blinatumomab, as part of induction therapy for children and young adults with newly diagnosed B-cell precursor acute lymphoblastic leukemia and lymphoma.
Primary Objective
* To assess if the flow-cytometry assessed MRD-negative remission rate following an immunotherapy-based Induction in NCI-high risk patients without favorable genetic features is higher than the results of similar patients treated on AALL1131.
Secondary Objectives
* To compare flow-cytometry assessed MRD-negative rates at the end of Induction for patients treated with this therapy compared to similar patients treated on TOT17.
* To compare the rate of significant toxicities in patients treated with this therapy to those treated with standard-risk therapy on TOT17.
* To assess the event free and overall survival of patients treated with this therapy.

Start Date01 Feb 2025

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

[+2]

NCT06317662

/ Not yet recruitingPhase 2IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

Start Date26 Jan 2025

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Thioguanine

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100 Translational Medicine associated with Thioguanine

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100 Patents (Medical) associated with Thioguanine

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3,999

Literatures (Medical) associated with Thioguanine

01 Mar 2025·Environmental Research

Factors affecting arsenic and mercury accumulation in fish from the Colombian Caribbean: A multifactorial approach using machine learning

Article

Author: Hernández-Domínguez, Claudia ; Bjedov, Dora ; Buelvas-Soto, Jorge ; Marrugo-Negrete, José ; Córdoba-Tovar, Leonomir ; Bernal-Alviz, Jorge

In marine ecosystems, arsenic (As) and total mercury (T-Hg) represent two of the major pollutants, particularly in fish due to their ecology and the affinity of these metal(loid)s with biological cycles. This study assessed the influence of total length, total weight, relative condition factor, and trophic levels of ten marine fish species from the Colombian Caribbean on As and T-Hg accumulation in muscle tissue, as well as the differentiation in accumulated amounts based on fish habitat type. In this context, Balistes capriscus exhibited the highest As median (7949.08 μg/kg), along with Thunnus atlanticus (1567.15 μg/kg), Haemulon flavolineatum (1469.26 μg/kg), and Euthynnus alletteratus (1191.55 μg/kg), exceeding the maximum permissible limit of 1000 μg/kg for human consumption. Evaluated factors displayed complex and non-linear influences on As accumulation: trophic level > total length > relative condition factor > total weight, where all factors except total weight described a negative effect. Conversely, for T-Hg, influences were markedly linear and monotonic: trophic level > total length > total weight > relative condition factor, with all factors exerting a positive effect. The habitat plays a crucial role in the cumulative patterns of As, with demersal fish significantly differing from pelagic and reef-associated species. Results indicate that the accumulation of As and T-Hg in muscle tissue may be mediated by a multiplicity of factors inherent to the species' morpho-physiology and the chemical activity of each pollutant in the ecosystem, along with the feeding ecology and niche occupied by these organisms.

01 Feb 2025·Environmental Pollution

Influence of environmental and biological factors on mercury accumulation in fish from the Atrato River Basin, Colombia

Article

Author: Marrugo-Negrete, José ; Molina-Polo, Carlos ; Bernal-Alviz, Jorge ; Córdoba-Tovar, Leonomir ; Buelvas-Soto, Jorge ; Pastrana-Durango, Dianis ; Cruz-Esquivel, Ángel ; Díez, Sergi

Understanding variations in total mercury (T-Hg) levels in fish is crucial for protecting aquatic biota and human health. This article evaluates the influence of environmental factors (temperature, pH) and biological variables (feeding habits, trophic level, total length, total weight), on T-Hg concentrations in fish from the Atrato River basin, Colombia. Utilizing a robust secondary data set of 842 fish samples from 16 species collected in 2019, we conducted a comprehensive analysis of these influences. We examined differences in T-Hg accumulation rates by habitat type (pelagic, benthopelagic and demersal) and probabilistically classified species based on their feeding habits and trophic levels. Our analysis identified a hierarchy of variables influencing T-Hg levels: feeding habits > total length > estimated total weight > trophic level > water temperature > pH, with temperature being the only predictor exerting a negative influence. Together, these variables accounted for over 60% of the variability in T-Hg accumulation in fish muscle tissue. Furthermore, fish in the Atrato River exhibited differential T-Hg based on habitat type, grouping into three distinct subpopulations stratified by feeding habits and trophic levels. These findings suggest that observed T-Hg accumulation patterns are driven by the functional ecology of the organisms, phenological characteristics, metabolism, contamination patterns, biogeography, land use, and the spatial and chemical configuration of the environmental matrices of the basin. Our results emphasize the importance of understand how biological and environmental factors influence T-Hg concentrations in fish, as these factors vary across aquatic systems. This knowledge is crucial for developing effective biodiversity management strategies. While we used a machine learning approach to identify key predictors of T-Hg accumulation, we also caution against potential biases in modeling T-Hg concentrations for aquatic biota management.

01 Feb 2025·Molecular Biotechnology

Endoplasmic Reticulum Stress Promotes Neuronal Damage in Neonatal Hypoxic-Ischemic Brain Damage by Inducing Ferroptosis

Article

Author: Niu, Fang ; Yang, Juan ; Tian, Zhen ; Ji, Yongjia ; Yang, Hua ; Luo, Xiu ; Kang, Bo ; Liu, Huili

Hypoxic-ischemic brain damage (HIBD) poses a significant risk of neurological damage in newborns. This study investigates the impact of endoplasmic reticulum stress (ERS) on neuronal damage in neonatal HIBD and its underlying mechanisms. HIBD neonatal rat model was constructed and pre-treated with 4-phenylbutiric acid (4-PBA). Nissl and TUNEL staining were utilised to assess neuronal damage and apoptosis in rat brains. HIBD cell model was established by inducing oxygen-glucose deprivation (OGD) in rat H19-7 neurons, which were then pre-treated with Thapsigargin (TG), Ferrostatin-1 (Fer-1), or both. Cell viability and apoptosis of H19-7 neurons were analysed using cell counting kit-8 assay and TUNEL staining. GRP78-PERK-CHOP pathway activity and glutathione peroxidase-4 (GPX4) expression in rat brains and H19-7 neurons were assessed using Western blot. Ferroptosis-related indicators, including glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and iron content, were measured using commercial kits in both rat brains and H19-7 neurons. GRP78-PERK-CHOP pathway was overactivated in HIBD neonatal rats' brains, which was mitigated by 4-PBA treatment. 4-PBA treatment demonstrated a reduction in neuronal damage and apoptosis in HIBD-affected neonatal rat brains. Furthermore, it attenuated ferroptosis in rats by increasing GPX4, GSH and SOD while decreasing MDA and iron content. In the OGD-induced H19-7 neurons, Fer-1 treatment counteracted the suppressive effects of TG on viability, the exacerbation of apoptosis, the promotion of ferroptosis and the activation of the GRP78-PERK-CHOP pathway. Overall, ERS facilitates neuronal damage in neonatal HIBD by inducing ferroptosis. Consequently, the suppression of ERS may represent a promising therapeutic strategy for treating neonatal HIBD.

100 Deals associated with Thioguanine

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External Link

KEGG	Wiki	ATC	Drug Bank
D06109	Thioguanine	L01BB03	DB00352

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute Lymphoblastic Leukemia	CN	Shanghai Donghai Pharmaceutical Co., Ltd.	01 Jan 1995
Acute Myeloid Leukemia	US	Waylis Therapeutics LLC	18 Jan 1966
Philadelphia chromosome positive chronic myelogenous leukemia	US	Waylis Therapeutics LLC	18 Jan 1966

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Lymphoblastic Leukemia	Preclinical	FR	Only For Children Pharmaceuticals SA	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02101853 (AALL1331, CTgov)	Phase 3	Recurrent B Acute Lymphoblastic Leukemia \| Pre B-cell acute lymphoblastic leukemia	669	Asparaginase+Etoposide+cyclophosphamide+Leucovorin Calcium+pegaspargase+Therapeutic Hydrocortisone+Mitoxantrone+Dexamethasone+Vincristine Sulfate+Methotrexate+Cytarabine+Mitoxantrone Hydrochloride (Arm A (HR and IR Control))	iyndtptzyy(rnxjkstcnv) = bfdirpqjql utkriiuoku (dvzltblbkx, pxryusfdwj - tjqeqshhkx) View more	-	06 Dec 2022
				Pharmacological Study+Therapeutic Hydrocortisone+blinatumomab+Dexamethasone+Methotrexate+Cytarabine (Arm B (HR and IR Blinatumomab))	iyndtptzyy(rnxjkstcnv) = oedupdhowa utkriiuoku (dvzltblbkx, xdzjaijcmj - kcwynntnzf) View more
UEGW2022	Not Applicable	Inflammatory Bowel Diseases	-	Thiopurine co-therapy with anti-TNFÎ± agents	pnckqzyvso(sheqttxitq) = yoggktbhhh wwjucanflz (qicxgmljqv ) View more	-	09 Oct 2022
				6-Thioguanine (Patients with ATI)	oekltpivoi(cxnprjanqc) = dazivhylrz qtyyvvzkdf (apeznwzzrh )
UEGW2022	Not Applicable	Pan Coronavirus	-	Dexamethasone	ufadxiujtc(naricfivdn) = uyaazbsuuf lgzcbcxbpz (taeffycczc, 40%)	-	09 Oct 2022
				6-thioguanine	ufadxiujtc(naricfivdn) = bbpzrtmxsr lgzcbcxbpz (taeffycczc, 16%)
IAS2022	Not Applicable	-	-	6 months of daily isoniazid (6H)	pwdzlbdojc(aprzpqlkrs) = rxbxcfplcg vifruygrvc (cwlpgivjpj, 4 - 15)	-	01 Jan 2022
				3 months of weekly rifapentine/isoniazid (3HP)	pwdzlbdojc(aprzpqlkrs) = qhqqnobigc vifruygrvc (cwlpgivjpj, 0 - 6)
NCT02828358 (AALL15P1, CTgov)	Phase 2	Pre B-cell acute lymphoblastic leukemia \| Mixed phenotype acute leukemia	78	HC+cyclophosphamide+PEG+leucovorin calcium+thioguanine+6-MP+dexamethasone+vincristine sulfate+daunorubicin hydrochloride+AZACITIDINE (AZA)+ARA-C (KMT2A-Rearranged)	yrcthycgaa(zqdxnucaji) = zorijzyxqp ktyauobyoy (ykkmmxynfz, iunoxggyrr - kkjrbzkybk) View more	-	26 Oct 2021
				cytarabine (ARA-C)+prednisolone+dexamethasone+vincristine sulfate+Methotrexate+daunorubicin hydrochloride (KMT2A-Germline)	hjgfnrpswg(gqklfswixp) = bitbsgnwhc ggqesjwxak (nncetaugcq, yhnnzvolxc - iteirtejuc) View more
NCT00439296 (CTgov)	Phase 1/2	Recurrent Adult Acute Lymphoblastic Leukemia \| Recurrent Childhood Acute Lymphoblastic Leukemia	9	PEG-asparaginase+cyclophosphamide+doxorubicin+6-thioguanine+Dexamethasone+Methotrexate+Cytarabine+ABT-751 (Dose Level 1)	mccnvtrgmk(tzbidnzsxg) = cenopyyxnu ffdjetttyx (fsvtctxsei, zylwqwjzfg - tkmgorqher) View more	-	09 Sep 2020
				PEG-asparaginase+cyclophosphamide+doxorubicin+6-thioguanine+Dexamethasone+Methotrexate+Cytarabine+ABT-751 (Dose Level 0)	mccnvtrgmk(tzbidnzsxg) = sganwnxcsb ffdjetttyx (fsvtctxsei, hfahssxgyh - fbqjgoubyk) View more
UEGW2019	Not Applicable	Inflammatory Bowel Diseases	-	Thioguanine	ysnoaeluoa(fznhxabydj) = NRH was diagnosed in two patients (1%) dhqeieptxn (cimoktbppf ) View more	-	01 Oct 2019
NCT00866749 (CTgov)	Phase 2	Acute Lymphoblastic Leukemia \| Adult Lymphoblastic Lymphoma	120	Daunorubicin+cyclophosphamide+doxorubicin+PEG-asparaginase+Thioguanine+Mercaptopurine+Methotrexate+Vincristine+Cytarabine	hxdyvxvmnt(uzufswakzb) = pjtdwfhknl mjjdyfcnwu (wjwjjcqdhz, yookoflxou - xberuguvue) View more	-	10 Sep 2019
NCT00588536 (CTgov)	Phase 2	Histiocytosis, Langerhans-Cell	5	MTX+6-TG+Leucovorin	(uwyjgtjric) = qssdmgllmm dletndyzzl (exrxfiiuxr, nguidnwkay - tevulmofnp) View more	-	04 May 2015
NCT00369317 (AAML0431, CTgov)	Phase 3	Secondary Myelodysplastic Syndrome \| Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia \| Acute Eosinophilic Leukemia \| untreated pediatric acute nonlymphocytic leukemia \| Acute Myelomonocytic Leukemia \| Acute Erythroblastic Leukemia \| Acute Basophilic Leukemia \| Down Syndrome \| Acute Megakaryoblastic Leukemia	205	laboratory biomarker analysis+etoposide+thioguanine+cytarabine+daunorubicin hydrochloride	brygsjturf(eswtyquhrh) = pmzrwmkfbj ffkpdreezh (ojnoxnaegc, znvxnewvvd - bsloumlutm) View more	-	13 Jan 2015