Delving into the Latest Updates on Teniposide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4'-demethylepipodophyllotoxin 9-(4,6-O-(R)-2-thenylidene-beta-D-glucopyranoside), Epidophyllotoxin, ETP

+ [6]

Target

Top II

Mechanism

Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [3]

Active Indication

Acute Lymphoblastic LeukemiaAstrocytomaBladder Cancer+ [2]

Inactive Indication-

Originator Organization

HQ Specialty Pharma Corp.

Active Organization

China Resources Double-Crane Pharmaceutical Co., Ltd.

Inactive Organization

HQ Specialty Pharma

Drug Highest PhaseApproved

First Approval Date

US (14 Jul 1992),

Acute Lymphoblastic Leukemia

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC32H32O13S

InChIKeyNRUKOCRGYNPUPR-QBPJDGROSA-N

CAS Registry29767-20-2

Hemophagocytic lymphohistiocytosis (HLH) is a highly inflammatory disease involving cytokine storms and is characterised by rapid progression and high mortality. There are no uniform clinical criteria for the diagnosis of CNS-HLH.And there is still a lack of international consensus on the treatment for CNS-HLH. Following allogeneic HSCT after HLH induction therapy is recommended for CNS-HLH. One of the major factors influencing the transplantation effect is conditioning. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of Teniposide incorporating Bu/Cy conditioning regimen followed by allogeneic hematopoietic stem cell transplantation for HLH with central nervous system involvement.

Start Date22 Oct 2023

Sponsor / Collaborator

Beijing Friendship Hospital

ChiCTR2300073961 / SuspendedPhase 4IIT

A single-arm, open, multicenter clinical study to evaluate the efficacy and safety of teniposide combined with cisplatin or carboplatin in recurrent high-grade glioma.

Start Date31 Jul 2023

Sponsor / Collaborator-

100 Clinical Results associated with Teniposide

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100 Translational Medicine associated with Teniposide

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100 Patents (Medical) associated with Teniposide

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1,401

Literatures (Medical) associated with Teniposide

31 Dec 2024·Emerging microbes & infections

Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China

Article

Author: Jiang, Yan ; Zhao, Dongdong ; Yu, Yunsong ; Zhang, Ping ; Wang, Yinping ; Shi, Qiucheng ; Hu, Huangdu

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.

01 Dec 2024·EUROPEAN JOURNAL OF CANCER

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Article

Author: Jansen, Patty M ; Zijlstra, Josée M ; Diepstra, Arjan ; Oudshoorn, Mirjam A ; Brink, Mirian ; Doorduijn, Jeanette K ; Bohmer, Lara H. ; Neelis, Karen J. ; van den Brand, Michiel ; Mühlebner, Angelika ; van Rooij, Sjo L M ; Oostvogels, Rimke S ; Durian, Marc F ; Chamuleau, Martine E D ; Jansen, Patty M. ; Bohmer, Lara H ; Nicolae, Alina ; te Boome, Liane C.J. ; Woei-A-Jin, F.J. Sherida H. ; de Groen, Ruben A.L. ; Tousseyn, Thomas ; Neelis, Karen J ; Bromberg, Jacoline C E ; Te Boome, Liane C J ; Nijland, Marcel ; de Groen, Ruben A L ; de Groot, Fleur A. ; Dierickx, Daan ; Terpstra, Valeska ; Woei-A-Jin, F J Sherida H ; Stavast, Jeroen ; de Haan, Lorraine M ; Bromberg, Jacoline C.E. ; de Haan, Lorraine M. ; Veelken, Hendrik ; Doorduijn, Jeanette K. ; van der Poel, Marjolein W.M. ; Posthuma, Eduardus F.M. ; Stevens, Wendy B C ; Stevens, Wendy B.C. ; Oudshoorn, Mirjam A. ; Böhringer, Stefan ; Zijlstra, Josée M. ; de Groot, Fleur A ; Oostvogels, Rimke S. ; Noordenbos, Troy ; Chamuleau, Martine E.D. ; Hamid, Myrurgia Abdul ; Dekker, Tim J A ; van Rooij, Sjo L.M. ; Kersten, Marie José ; Sijs-Szabo, Aniko ; Dekker, Tim J.A. ; Koens, Lianne ; van der Poel, Marjolein W M ; Lam, King H ; Vermaat, Joost S P ; Vermaat, Joost S.P. ; Durian, Marc F. ; de Weerdt, Okke ; Posthuma, Eduardus F M ; Beeker, Aart ; Lam, King H.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m²/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

01 Nov 2024·3 Biotech

Pharmacokinetic predictions of ROS-mediated targets and genotoxin combinations via multiple ligand simultaneous docking and ROS evaluation in vitro using HepG2 cell lines

Article

Author: Rajaguru, Palanisamy ; Issac, Praveen Kumar ; Sri Snehaa, C P ; Sri Snehaa, C. P. ; Pugalenthi, Velan

Although combination therapy is known for its high efficacy, reduced side effects and drug resistance, toxicity remains a major drawback. Some of the genes are likely to induce hepatotoxicity through ROS-mediated mechanisms when a drug is metabolized alone or in combination in the liver. To address this, we have developed a scientific approach to predict the toxicity of different genotoxin combinations and validate their interactions with various targets. The current study is an extensive study of our previous set of in vivo rat liver microarray data processed using R studio for their functional analysis. About five combinations of genotoxins such as CPT/ETP, CPT/CPL, ETP/CPL, CP/CPT and EES/CP along with their differential gene expression targeting Chemical carcinogenesis-ROS are chosen for this study. We aim to examine the binding affinity of different genotoxin combinations using in silico multiple ligand simultaneous docking (MLSD) and are then bio-evaluated for cytotoxicity in vitro using human hepatocellular carcinoma cell lines (HepG2) with the MTT assay. As a result, dose-response cytotoxicity with its strength of interactions and a significant variance in ROS levels in the treated cells is observed compared to their IC₅₀ values. Out of 5 combinations such as CPT/CPL, ETP/CPL and EES/CP are found not only to be significantly cytotoxic but also induce oxidative stress specifically above their IC₅₀ values with good and moderate binding interactions ensuring their toxicity. On the contrary, the safe combinations are found to be CTP/ETP and CP/CPT possibly with no and tolerable adverse effects standing as preliminary information for researchers in drug design and development.

100 Deals associated with Teniposide

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External Link

KEGG	Wiki	ATC	Drug Bank
D02698	Teniposide	L01CB02	DB00444

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Astrocytoma	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	01 Jan 1999
Bladder Cancer	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	01 Jan 1999
Lymphoma	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	01 Jan 1999
Neuroblastoma	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	01 Jan 1999
Acute Lymphoblastic Leukemia	US	HQ Specialty Pharma	14 Jul 1992

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01960192 (Pubmed \| J Neurooncol) Manual	Phase 2	Primary Central Nervous System Lymphoma BCL6 Overexpression	49	Fotemustine+teniposide+dexamethasone	lhszxumxwm(unoesvlodu) = gpqknlkwwr gekkjwfspv (czacrznvng ) View more	Positive	01 Nov 2018
NCT01960192 (Pubmed \| J Neurooncol) Manual	Phase 2	Primary Central Nervous System Lymphoma BCL6 Overexpression	49	methotrexate+cytarabine	lhszxumxwm(unoesvlodu) = bfwuyuedyj gekkjwfspv (czacrznvng ) View more	Positive	01 Nov 2018
ASCO2004	Phase 2	metastatic non-small cell lung cancer	-	Concurrent chemotherapy (teniposide and carboplatin) combined with whole brain radiotherapy	nphathjrcj(xbagnciert) = neutropoenia, thromocytopoenia, anaemia laquyafwxl (hwvbpswgnv )	-	15 Jul 2004