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

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.

[+1]

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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150

Literatures (Medical) associated with Lestaurtinib

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.

01 Mar 2024·Journal of Cellular and Molecular Medicine

Lestaurtinib potentiates TRAIL‐induced apoptosis in glioma via CHOP‐dependent DR5 induction

Yingxiao Cao, Shiqi Kong, Yuling Xin, Yan Meng, Shuling Shang, Yanhui Qi. Lestaurtinib potentiates TRAIL‐induced apoptosis in glioma via CHOP‐dependent DR5 induction. J Cell Mol Med. 2020; 24: 7829–7840. https://doi-org.libproxy1.nus.edu.sg/10.1111/jcmm.15415.The above article, published online on 22 May 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine, and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplications of images between this and other articles that were either previously published or published later in the same year in a different scientific context. Thus, the editors consider the conclusions of this manuscript substantially compromised.

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	Preclinical	PL	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Preclinical	RO	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Preclinical	SE	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)	zgchtrlsrb(pbmnzbwhen) = vsaoqctfhk arygpkoxqv (rlnqclkojl, orcisukaso - ypyjhqykzc) 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)	zgchtrlsrb(pbmnzbwhen) = ovkdrfjoqu arygpkoxqv (rlnqclkojl, ujotlefdnn - qxozdnwqgv) View more	-	20 Dec 2013
NCT00494585 (CTgov)	Phase 2	Myelofibrosis \| Leukemia \| Primary Myelofibrosis	27	CEP-701	(gwjqnngqyq) = pxqguclifm oxtwtyqted (afudreapqx, pvfjbjxijf - qxsydxovmp) View more	-	04 May 2011
NCT00079482 (Pubmed \| Circulation)	Phase 2	Acute Myeloid Leukemia	224	Chemotherapy alone	(itehlwyyon) = nvvibwntqd gkcwubcjti (ighvnjuqxm )	Negative	24 Mar 2011
NCT00079482 (Pubmed \| Circulation)	Phase 2	Acute Myeloid Leukemia	224	Chemotherapy followed by lestaurtinib	(itehlwyyon) = fvoopebanh gkcwubcjti (ighvnjuqxm )	Negative	24 Mar 2011
ASCO2010	Phase 1	Refractory Neuroblastoma	47	Lestaurtinib	vmqkamwwvc(gsgpdvlycl) = qzlpruxvhr jmatkgummv (sibzyarmai )	-	20 May 2010
NCT00494585 (Pubmed \| Circulation)	Phase 2	Post-essential thrombocythemia myelofibrosis	22	CEP-701 80 mg	kasytgduxm(hojfqvtrew) = diarrhea, any grade, 72%; grade 3 or 4, 9%; nausea, grade 1 or 2 only, 50%; vomiting, grade 1 or 2 only, 27% gutprofikf (pwoobeoayx ) View more	-	11 Feb 2010