Delving into the Latest Updates on Lestaurtinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Lestaurtinib (USAN/INN)

+ [5]

Target

FLT3 x JAK2 x TrkA x TrkB x TrkC

Mechanism

FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors), JAK2 inhibitors(Tyrosine-protein kinase JAK2 inhibitors), TrkA antagonists(Nerve growth factor receptor Trk-A antagonists)

+ [2]

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

Acute Lymphoblastic Leukemia

Inactive Indication

Castration-Resistant Prostatic CancerMultiple MyelomaMyelofibrosis+ [6]

Originator Organization

Kyowa Kirin Co., Ltd.

Active Organization

Kyowa Kirin Co., Ltd.

Cephalon, Inc.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC26H21N3O4

InChIKeyUIARLYUEJFELEN-LROUJFHJSA-N

CAS Registry111358-88-4

This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.

Start Date15 Jan 2008

Sponsor / Collaborator

The Children's Oncology Group Foundation, Inc.

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100 Clinical Results associated with Lestaurtinib

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100 Translational Medicine associated with Lestaurtinib

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100 Patents (Medical) associated with Lestaurtinib

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164

Literatures (Medical) associated with Lestaurtinib

20 Dec 2024·Journal of Biomolecular Structure and Dynamics

The promising impact of Bemcentinib and Repotrectinib on sleep impairment in Alzheimer’s disease

Article

Author: Ramezani, Fatemeh ; Ariaei, Armin

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, demands effective medication to alleviate symptoms. This study focused on sleep impairment as an overt clinical symptom and tauopathy as a prominent molecular symptom of this disease. Multiple compounds from three biomolecule libraries (719 compounds; ChemDiv:366 - ChEMBL:180 - PubChem:173) were evaluated for potential binding affinity and safety using AutoDock Vina and pkCSM, respectively, resulting in the selection of four candidate compounds (Lestaurtinib, Repotrectinib, Bemcentinib, and Zotiraciclib). Due to the similarity of Repotrectinib and Bemcentinib binding sites to ATP, 300 ns Martini 3 coarse-grained molecular dynamics (MD) was performed on these two molecules and ATP by NAMD. The stability of tau protein in the presence of drugs was assessed using a 200 ns Martini 3 MD simulation. Binding site analysis discloses Bemcentinib and Repotrectinib as two inhibitors occupying most amino acids in binding with ATP. The RMSD and RMS average correlation results revealed protein containing Bemcentinib and Repotrectinib to have a more stable state compared to ATP in the first 220 ns simulation. There was only a single detachment of Bemcentinib, while Repotrictinib detached twice at the end of the simulation. Eventually, adding Bemcentinib and Repotrectinib to the enzyme-tau complex significantly increased the number of tau detachments during the 200 ns simulation. We report Bemcentinib and Repotrectinib, formerly prescribed for cancer, as potential inhibitors of the CK1 δ. Besides their high binding affinity compared to ATP, they can inhibit all ATP-binding sites and alter the tau binding stability.Communicated by Ramaswamy H. Sarma.

03 May 2024·Expert Review of Molecular Diagnostics

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma

Article

Author: Zhang, Qi ; Wang, Xiaobo ; Tang, Bo ; Zhao, Hua ; Guan, Mingze ; Li, Li

BACKGROUNDAlthough anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL).METHODSWe obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay.RESULTSThe high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL.CONCLUSIONThe ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

01 Apr 2024·iScience

Inference of drug off-target effects on cellular signaling using interactome-based deep learning

Article

Author: Meimetis, Nikolaos ; Lauffenburger, Douglas A ; Nilsson, Avlant

Many diseases emerge from dysregulated cellular signaling, and drugs are often designed to target specific signaling proteins. Off-target effects are, however, common and may ultimately result in failed clinical trials. Here we develop a computer model of the cell's transcriptional response to drugs for improved understanding of their mechanisms of action. The model is based on ensembles of artificial neural networks and simultaneously infers drug-target interactions and their downstream effects on intracellular signaling. With this, it predicts transcription factors' activities, while recovering known drug-target interactions and inferring many new ones, which we validate with an independent dataset. As a case study, we analyze the effects of the drug Lestaurtinib on downstream signaling. Alongside its intended target, FLT3, the model predicts an inhibition of CDK2 that enhances the downregulation of the cell cycle-critical transcription factor FOXM1. Our approach can therefore enhance our understanding of drug signaling for therapeutic design.

100 Deals associated with Lestaurtinib

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External Link

KEGG	Wiki	ATC	Drug Bank
D04696	Lestaurtinib	-	DB06469

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Lymphoblastic Leukemia	Phase 3	-	Kyowa Kirin Co., Ltd.	-
Acute Lymphoblastic Leukemia	Phase 3	-	Cephalon, Inc.	-
Acute Lymphoblastic Leukemia	Phase 2	AU	-	-
Acute Lymphoblastic Leukemia	Phase 2	US	-	-
Acute Lymphoblastic Leukemia	Phase 2	NZ	-	-
Acute Lymphoblastic Leukemia	Phase 2	CA	-	-
Pancreatic Cancer	Phase 2	US	Cephalon, Inc.	-
Relapsing acute myeloid leukemia	Discovery	CA	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Discovery	IL	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Discovery	RO	Cephalon, Inc.	01 Oct 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00469859 (CTgov)	Phase 1/2	Relapsing acute myeloid leukemia	14	lestaurtinib+cytarabine+Idarubicin (Group 1 (Lestaurtinib Dose 50 mg/m2)	(gpzwmmowqp) = sotmgzlajn hbchdfhirp (srhokcfway, mozrvyucvp - gxiumbqabt) View more	-	20 Dec 2013
NCT00469859 (CTgov)	Phase 1/2	Relapsing acute myeloid leukemia	14	lestaurtinib+cytarabine+Idarubicin (Group 2 (Lestaurtinib: Dose 62.5 mg/m2)	(gpzwmmowqp) = itdyqbnpen hbchdfhirp (srhokcfway, dtvsnfynzd - mgqiobsebl) View more	-	20 Dec 2013
NCT00494585 (CTgov)	Phase 2	Myelofibrosis \| Leukemia \| Primary Myelofibrosis	27	CEP-701	(erdzvgvjmw) = yezqxumgiw jbshtewayb (cioslcdnsz, tprgxjkskq - uxtilflnvd) View more	-	04 May 2011
ASCO2010	Phase 1	Refractory Neuroblastoma	47	Lestaurtinib	gjdkrxiqlu(memvijpxti) = pjiezaiyio bfazzxsmxv (cojhfrowim )	-	20 May 2010