Delving into the Latest Updates on Tandutinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tandutinib (USAN/INN), 坦度替尼

+ [6]

Target

FLT3 x PDGFRα x PDGFRβ x c-Kit

Mechanism

FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors), PDGFRα inhibitors(Platelet-derived growth factor receptor alpha inhibitors), PDGFRβ inhibitors(Platelet-derived growth factor receptor beta inhibitors)

+ [1]

Therapeutic Areas

NeoplasmsNervous System DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaGlioblastomaGlioblastoma Multiforme+ [2]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Millennium Pharmaceuticals, Inc.

Takeda Pharmaceutical Co., Ltd.

Millennium Biotechnologies, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC31H42N6O4

InChIKeyUXXQOJXBIDBUAC-UHFFFAOYSA-N

CAS Registry387867-13-2

This is a safety study of tandutinib in combination with temozolomide and bevacizumab after people have received radiation therapy and temozolomide treatment. This study will determine the maximum safe dose of tandutinib when combined with temozolomide and bevacizumab and evaluate the safety of the combination treatment.

Start Date01 Jun 2009

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

NCT00379080 / CompletedPhase 1/2IIT

A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Start Date01 Jan 2007

Sponsor / Collaborator

National Cancer Institute

NCT00408902 / CompletedPhase 2IIT

Phase II Study of MLN518 in Patients With Metastatic Clear Cell Renal Cell Carcinoma

This phase II trial is studying how well tandutinib works in treating patients who have undergone surgery for metastatic kidney cancer. Tandutinib may stop the growth of kidney cancer by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving tandutinib after surgery may kill any tumor cells that remain after surgery.

Start Date01 Nov 2006

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Tandutinib

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100 Translational Medicine associated with Tandutinib

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100 Patents (Medical) associated with Tandutinib

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47

Literatures (Medical) associated with Tandutinib

18 Jul 2023·Journal of molecular modeling

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies.

Article

Author: Savardashtaki, Amir ; Mirmajidi, Seyedeh Habibeh ; Nezafat, Navid ; Ghasemi, Younes ; Negahdaripour, Manica ; Irajie, Cambyz

BACKGROUNDThe bacterium Bacillus coagulans has attracted interest because of its ability to produce spores and advantageous probiotic traits, such as facilitating food digestion in the intestine, managing some disorders, and controlling the symbiotic microbiota. Spore-forming probiotic bacteria are especially important in the probiotic industry compared to non-spore-forming bacteria due to their stability during production and high resistance to adverse factors such as stomach acid. When spore-forming bacteria are exposed to environmental stresses, they enter the sporulation pathway to survive. This pathway is activated by the final phosphorylation of the master regulator of spore response, Spo0A, and upon achieving the phosphorylation threshold. Spo0A is indirectly inhibited by some enzymes of the aspartate response regulator phosphatase (Rap) family, such as RapJ. RapJ is one of the most important Rap enzymes in the sporogenesis pathway, which is naturally inhibited by the pentapeptides.METHODSThis study used structure-based virtual screening and molecular dynamics (MD) simulation studies to find potential RapJ hits that could induce the sporulation pathway. The crystal structures of RapJ complexed with pentapeptide clearly elucidated their interactions with the enzyme active site.RESULTSBased on the binding compartment, through molecular docking, MD simulation, hydrogen bonds, and binding-free energy calculations, a series of novel hits against RapJ named tandutinib, infigratinib, sitravatinib, linifanib, epertinib, surufatinib, and acarbose were identified. Among these compounds, acarbose obtained the highest score, especially in terms of the number of hydrogen bonds, which plays a major role in stabilizing RapJ-ligand complexes, and also according to the occupancy percentages of hydrogen bonds, its hydrogen bonds were more stable during the simulation time. Consequently, acarbose is probably the most suitable hit for RapJ enzyme. Notably, experimental validation is crucial to confirm the effectiveness of the selected ligands.

01 Aug 2022·Nanomedicine: Nanotechnology, Biology and Medicine

Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment

Article

Author: Zhao, Linyao ; Zhang, Si ; Qi, Yangzhi ; Chen, Qianxue ; Zhang, Shenqi ; Li, Yong ; Jiang, Hongxiang ; Sun, Qian ; Tong, Shiao ; Gao, Lun ; Cai, Jiayang ; Xu, Yang ; Wang, Yixuan ; Ye, Zhang ; Yan, Tengfeng

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.

28 Sep 2021·British Journal of CancerQ1 · MEDICINE

CCT245718, a dual FLT3/Aurora A inhibitor overcomes D835Y-mediated resistance to FLT3 inhibitors in acute myeloid leukaemia cells

Q1 · MEDICINE

Article

Author: Linardopoulos, Spiros ; Muddassar, Muhammad ; Saleem, Rahman Shah Zaib ; Parveen, Hira ; Tariq, Muhammad Usama ; Bavetsias, Vassilios ; Ullah, Rahim ; Faisal, Amir ; Furqan, Muhammad

BACKGROUNDActivating mutations in the Fms-like tyrosine kinase 3 (FLT3) are among the most prevalent oncogenic mutations in acute myeloid leukaemia. Inhibitors selectively targeting FLT3 kinase have shown promising clinical activity; their success in the clinic, however, has been limited due to the emergence of acquired resistance.METHODSCCT245718 was identified and characterised as a dual Aurora A/FLT3 inhibitor through cell-based and biochemical assays. The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to FLT3 inhibitors.RESULTSCCT245718 exhibits potent antiproliferative activity towards FLT3-ITD + AML cell lines and strongly binds to FLT3-ITD and TKD (D835Y) mutants in vitro. Activities of both FLT3-ITD and Aurora A are also inhibited in cells. Inhibition of FLT3 results in reduced phosphorylation of STAT5, downregulation of survivin and induction of apoptotic cell death. Moreover, CCT245718 overcomes TKD-mediated resistance in a MOLM-13-derived cell line containing FLT3 with both ITD and D835Y mutations. It also inhibits FLT3 signalling in both parental and resistant cell lines compared to FLT3-specific inhibitor MLN518, which is only active in the parental cell line.CONCLUSIONSOur results demonstrate that CCT245718 is a potent dual FLT3/Aurora A inhibitor that can overcome TKD-mediated acquired resistance.

100 Deals associated with Tandutinib

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External Link

KEGG	Wiki	ATC	Drug Bank
D06005	-	-	DB05465

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 2	-	Millennium Pharmaceuticals, Inc.	01 Jun 2009
Acute Myeloid Leukemia	Phase 2	-	Millennium Pharmaceuticals, Inc.	27 Feb 2006
Acute Myeloid Leukemia	Phase 2	-	Millennium Pharmaceuticals, Inc.	27 Feb 2006
Myelodysplastic Syndromes	Phase 2	US	Millennium Pharmaceuticals, Inc.	01 May 2002
Glioblastoma	Phase 2	US	Millennium Biotechnologies, Inc.	-
Renal Cell Carcinoma	Phase 2	-	Takeda Pharmaceutical Co., Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00408902 (CTgov)	Phase 2	Neoplasm Metastasis \| Metastatic Clear Cell Renal Cell Carcinoma	10	laboratory biomarker analysis+tandutinib	(flnhdfevza) = kwmoimycje qtmazlhegl (nclkgnneyj, egmdkwsiih - wbzriintlu) View more	-	04 Feb 2015
NCT00390468 (Pubmed \| Cancer Chemother Pharmacol)	Phase 2	Bone metastases	18	Tandutinib 500 mg	clhlvxwjtb(ioeqohgxgq) = hfuslogftm wqfnqyvbhh (wfwcyzgusw )	-	01 Oct 2011
NCT00390468 (CTgov)	Phase 2	Pain \| Castration-Resistant Prostatic Cancer \| Bone metastases	18	Tandutinib	yjajtohqgd(nhfbsqgdys) = aeyencjqav fmnatvgcrn (srdvcimrhf, lpphwaeddo - udtrvvqzsg) View more	-	07 Jun 2011