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

Action

inhibitors

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.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H42N6O4

InChIKeyUXXQOJXBIDBUAC-UHFFFAOYSA-N

CAS Registry387867-13-2

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

NCT00390468

/ CompletedPhase 2IIT

A Phase II Study of Tandutinib (MLN518) in Androgen-Independent Prostate Cancer With Bone Metastases

RATIONALE: Tandutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well tandutinib works in treating patients with progressive prostate cancer and bone metastases.

Start Date01 Oct 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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134

Literatures (Medical) associated with Tandutinib

01 Jan 2025·European Journal of Medicinal Chemistry

Identification of inhibitors targeting the FLT3-ITD mutation through 4D-QSAR, in vitro, and in silico

Article

Author: Wei, Chaochun ; Wang, Juan ; Ji, CuiCui ; Yan, Hong ; Chu, Dongchen ; Zhong, Qidi ; Zhang, Xiaokun ; Zhang, Yu

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation is a key target for acute myeloid leukemia (AML) treatment. The second-generation inhibitors such as Gilteritinib still present off-target effects and associated side effects. Therefore, identifying novel FLT3-ITD inhibitors has become a promising strategy for AML treatment. In this study, a 4D-QSAR model was developed based on Gilteritinib and its analogues, and it was found that introducing hydrophobic bulky groups at the piperazine or piperidine of Gilteritinib would enhance the binding affinity to FLT3-ITD. So, three series of targeted compounds (A1-A5, B1-B5 and C1-C5) were designed and synthesized. The antiproliferative activity against MOLM-13 cells was evaluated in vitro. Compound A1 (IC₅₀ = 25.65 nM), with a cubane group at the piperazine position; Compounds B2 (IC₅₀ = 63.38 nM) and C2 (IC₅₀ = 54.96 nM), with a norbornene group at the piperidine position, showed the strongest inhibition in their series. Their IC₅₀ values were comparable to that of the positive control Gilteritinib (IC₅₀ = 22.37 nM). FLT3-ITD was confirmed as the degradation target through a kinase inhibition assay, where the IC₅₀ values were 2.12 nM (Compound A1), 1.29 nM (Compound B2), and 3.06 nM (Compound C2), which were comparable to that of Gilteritinib (IC₅₀ = 0.43 nM). Additionally, molecular docking and molecular dynamics (MD) simulations showed that Compounds A1, B2, and C2 had similar binding modes to that of Gilteritinib with more stable affinities. Overall, these results demonstrated that Compounds A1, B2, and C2 were promising inhibitors for targeting AML with FLT3-ITD mutation.

01 Jan 2025·Journal of Investigative Dermatology

Identifying Potential Drug Targets for Keloid: A Mendelian Randomization Study

Article

Author: Luo, Xusong ; Wang, Yinmin ; Yuan, Zhaoqi ; Liu, Fei ; Wang, Xiuxia ; Yang, Jun

Keloids are a skin fibrosis disease characterized by troublesome symptoms, a varying degree of recurrence and inevitable side effects from treatments. Thus, identifying their drug targets is necessary. A 2-sample Mendelian randomization analysis was conducted using proteins from the intersection of the deCODE database and "The Druggable Genome and Support for Target Identification and Validation in Drug Development" as the exposure variable. The outcome variable was based on recently published GWAS of keloids. Summary data-based Mendelian randomization and colocalization analysis was employed to distinguish pleiotropy from linkage. Candidate targets underwent drug target analysis. The primary findings were validated through single-cell RNA-sequencing data, Western Blot and immunofluorescence staining on keloids. Seven proteins were identified as potential drug targets for keloids. Among these proteins, Hedgehog-interacting protein, neurotrimin [NTM], KLKB1, and CRIPTO showed positive correlations with keloids, while PLXNC1, SCG3 and PDGFD exhibited negative correlations. Combined with the single-cell RNA-sequencing data, NTM, PLXNC1, and PDGFD were found highly expressed in the fibroblasts. NTM showed a significant increase in keloids as compared to normal scars. In accordance with the analysis, higher levels of protein expression of NTM in keloids compared to normal skin was observed. The identified proteins may be appealing drug targets for keloids treatment with a special emphasis on NTM.

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.

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.	01 Mar 2006
Acute Myeloid Leukemia	Phase 2	-	Millennium Pharmaceuticals, Inc.	01 Mar 2006
Myelodysplastic Syndromes	Phase 2	United States	Millennium Pharmaceuticals, Inc.	01 May 2002
Glioblastoma	Phase 2	United States	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	(qmbljzrwis) = ovjiiethsh xduwqkzmpb (aezojvumon, mnngrjorqa - uleprnnebr) View more	-	04 Feb 2015
NCT00390468 (Pubmed \| Cancer Chemother Pharmacol)	Phase 2	Bone metastases	18	Tandutinib 500 mg	kuxojcujhj(qiofxprydb) = gakwnkgisv nmdyqnjsok (awndruzktn )	-	01 Oct 2011
NCT00390468 (CTgov)	Phase 2	Pain \| Castration-Resistant Prostatic Cancer \| Bone metastases	18	Tandutinib	lkdgbrpvya(ppojpwdmuq) = oqallsozzl siqrxwhqpn (nrerdgolwz, ndieqezhjr - suvmgciquj) View more	-	07 Jun 2011