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 (United States)

Structure/Sequence

Molecular FormulaC26H21N3O4

InChIKeyUIARLYUEJFELEN-LROUJFHJSA-N

CAS Registry111358-88-4

Clinical Trials associated with Lestaurtinib

EUCTR2008-002317-40-DE

/ Not yet recruitingNot Applicable

A phase IIa, multi-center, randomized, double-blind, vehicle-controlled study to determine antipsoriatic efficacy and safety of topical CEP-701 (lestaurtinib) cream formulations in patients with psoriasis vulgaris - POC Psoriasis

Start Date17 Oct 2008

Sponsor / Collaborator

Perrigo Israel Pharmaceuticals Ltd.

EUCTR2005-002258-23-DE

/ Not yet recruitingNot Applicable

A Randomized, Open Label Study of Oral CEP-701 Administered in Sequence With Standard Chemotherapy to Patients With Relapsed Acute Myeloid Leukemia (AML) Expressing FLT 3 Activating Mutations - NA

Start Date23 Jan 2008

Sponsor / Collaborator

Cephalon, Inc.

NCT00557193

/ CompletedPhase 3IIT

A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807)

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

100 Translational Medicine associated with Lestaurtinib

100 Patents (Medical) associated with Lestaurtinib

389

Literatures (Medical) associated with Lestaurtinib

01 Mar 2025·STAR Protocols

Protocol to infer off-target effects of drugs on cellular signaling using interactome-based deep learning

Article

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

Drugs that target specific proteins often have off-target effects. We present a protocol using artificial neural networks to model cellular transcriptional responses to drugs, aiming to understand their mechanisms of action. We detail steps for predicting transcriptional activities, inferring drug-target interactions, and explaining the off-target mechanism of action. As a case study, we analyze the off-target effects of lestaurtinib on FOXM1 in the A375 cell line. For complete details on the use and execution of this protocol, please refer to Meimetis et al.¹.

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.

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.

News (Medical) associated with Lestaurtinib

14 Dec 2023

·synapse.patsnap.com

Deciphering NTRK Inhibitors and Keeping Up with Their Recent Developments

NTRK, also known as neurotrophic receptor tyrosine kinase, plays a crucial role in the human body. It is a family of proteins that are involved in the growth, development, and survival of nerve cells. NTRK receptors are activated by neurotrophins, which are a group of proteins that support the growth and maintenance of neurons. When NTRK receptors are activated, they initiate signaling pathways that regulate various cellular processes, including cell growth, differentiation, and survival. Dysregulation of NTRK signaling has been implicated in various diseases, including cancer and neurological disorders. Targeting NTRK receptors has emerged as a promising therapeutic approach in the pharmaceutical industry. All currently available NTRK inhibitors are Tropomyosin receptor kinase (Trk) inhibitors, some of which also have anti-ROS1 and ALK activity. NTRK inhibitors bind to Trk, thereby preventing ligand-Trk interaction and Trk activation, thus blocking the oncogenic activity of cancer cells overexpressing NTRK fusion proteins, thereby inducing cell apoptosis and inhibiting cell growth in tumor cells. Similar to other TKIs, the durability of first-generation NTRK inhibitors is often limited by mutations affecting NTRK inhibitor binding interactions, including primary and acquired resistance. Therefore, second-generation NTRK inhibitors have been developed to overcome these resistance mutations. Compared with first-generation NTRK inhibitors, second-generation NTRK inhibitors have a smaller molecular weight and a compact macrocyclic structure, which avoids the steric hindrance that prevents first-generation NTRK inhibitors from binding to the ATP binding site in solvent front, gatekeeper, and xDFG mutations. The analysis of the target NTRK reveals a competitive landscape with multiple companies actively developing drugs targeting NTRK. Bayer AG, Roche Holding AG, Bristol Myers Squibb Co., Exelixis, Inc., and Ipsen SA are among the companies growing fastest under this target. The indications for NTRK-targeted therapies cover a wide range of cancers, indicating the potential of these therapies in treating various types of tumors. Small molecule drugs, Synthetic peptides, and Monoclonal antibodies are progressing rapidly, while biosimilars pose intense competition around innovative drugs. The countries/locations developing fastest under the target NTRK include the United States, European Union, Japan, and China, with China showing significant progress. Overall, the target NTRK presents a promising opportunity for the pharmaceutical industry, with potential for further growth and development in the future. How do they work? NTRK inhibitors are a type of medication that target and inhibit the activity of neurotrophic receptor tyrosine kinases (NTRKs). NTRKs are a family of proteins that play a crucial role in the growth, development, and survival of nerve cells. They are involved in various cellular processes, including cell proliferation, differentiation, and survival. When NTRKs become abnormally activated or overexpressed, it can lead to uncontrolled cell growth and contribute to the development and progression of certain types of cancers. NTRK inhibitors work by specifically blocking the activity of these receptors, thereby inhibiting the signaling pathways that promote tumor growth and survival. These inhibitors have shown promising results in the treatment of cancers that harbor NTRK gene fusions, which are genetic alterations that result in the fusion of NTRK genes with other genes. This fusion leads to the constitutive activation of NTRK receptors and the promotion of cancer cell growth. By targeting NTRK receptors, inhibitors can help suppress the growth of cancer cells and potentially improve patient outcomes. NTRK inhibitors are considered a targeted therapy and are typically used in patients with advanced or metastatic cancers that have NTRK gene fusions. They may be prescribed as a standalone treatment or in combination with other anticancer therapies, depending on the specific cancer type and individual patient characteristics. List of NTRK Inhibitors The currently marketed NTRK inhibitors include: Repotrectinib Entrectinib Larotrectinib Sulfate Cabozantinib (s)-Malate Regorafenib Taletrectinib Lestaurtinib Tavilermide AK-1830 BEN-2293 For more information, please click on the image below. What are NTRK inhibitors used for? NTRK inhibitors are primarily used in certain rare tumors, such as infantile fibrosarcoma and secretory breast cancer. For more information, please click on the image below to log in and search. How to obtain the latest development progress of NTRK inhibitors? In the Synapse database, you can keep abreast of the latest research and development advances of NTRK inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

29 Nov 2023

·synapse.patsnap.com

Unveiling the Secrets of JAK2 Inhibitors: Stay Updated with the Latest Advances?

JAK2, or Janus kinase 2, is an enzyme that plays a crucial role in the human body's signaling pathways. It is primarily involved in the activation of cytokine receptors, which are responsible for regulating various cellular processes. JAK2 is particularly important in hematopoiesis, the process of blood cell formation, as it is involved in the signaling of several key cytokines that control the production and differentiation of blood cells. Dysregulation or mutations in JAK2 can lead to various hematological disorders, including myeloproliferative neoplasms. Understanding the role of JAK2 is essential for developing targeted therapies to treat these disorders and potentially other diseases influenced by cytokine signaling. Janus kinase 2 (JAK2) inhibitors are a type of medication that modulates the immune system by inhibiting the activity of the JAK2 enzyme, thereby interfering with the JAK-STAT signaling pathway in lymphocytes. They have revolutionized treatments for a range of disorders, such as myeloproliferative neoplasms, rheumatoid arthritis, inflammatory bowel disease, and multiple immune-driven dermatological diseases. The development of JAK2 inhibitors began with the identification of potential inhibitors that work by blocking its tyrosine gated ATP binding site. The first JAK inhibitor to reach clinical trials was tofacitinib, a specific inhibitor of JAK3 that also inhibits JAK1 and JAK2 to a lesser extent. The analysis of the current competitive landscape and future development of target JAK2 reveals a diverse range of companies, indications, drug types, and countries/locations involved in the development of JAK2-targeted drugs. Companies such as Incyte Corp., Eli Lilly & Co., Novartis AG, AbbVie, Inc., Pfizer Inc., GSK Plc, Bristol Myers Squibb Co., Swedish Orphan Biovitrum AB, Astellas Pharma, Inc., and Roche Holding AG are growing fastest under the current target, with drugs in various stages of development. The approved indications for JAK2-targeted drugs cover a wide range of diseases and conditions, indicating the potential therapeutic value of these drugs. Small molecule drugs and chemical drugs are progressing most rapidly, suggesting intense competition in the market. The countries/locations developing fastest include the United States, European Union, Japan, Norway, Liechtenstein, Iceland, China, Australia, Canada, United Kingdom, Switzerland, India, Kuwait, Spain, South Korea, Germany, Italy, France, Poland, and Israel. The progress in China highlights the country's growing presence in the pharmaceutical industry. Overall, the analysis indicates a competitive landscape and a promising future for the development of JAK2-targeted drugs. How do they work?JAK2 inhibitors are a type of medication that target the Janus kinase 2 (JAK2) enzyme. JAK2 is a protein involved in the signaling pathway of various cytokines and growth factors, playing a crucial role in the regulation of immune responses and blood cell production. These inhibitors work by blocking the activity of JAK2, thereby reducing the production of certain inflammatory mediators and suppressing abnormal cell growth. From a biomedical perspective, JAK2 inhibitors are primarily used in the treatment of myeloproliferative neoplasms (MPNs), a group of blood disorders characterized by the overproduction of blood cells. One of the most well-known MPNs is polycythemia vera, where there is an excessive production of red blood cells. JAK2 inhibitors help to control the symptoms associated with these disorders, such as enlarged spleen, fatigue, and blood clotting complications. Furthermore, JAK2 inhibitors have shown promise in the treatment of certain autoimmune diseases, such as rheumatoid arthritis and psoriasis, as well as in certain types of cancers, including certain forms of leukemia. By targeting the JAK2 enzyme, these inhibitors can help modulate the immune response and inhibit the abnormal cell growth associated with these conditions. It is important to note that JAK2 inhibitors are prescription drugs and should only be used under the guidance of a healthcare professional. They may have potential side effects, such as an increased risk of infections, anemia, and liver toxicity. Regular monitoring and follow-up with a healthcare provider are necessary while using JAK2 inhibitors to ensure their safe and effective use. List of JAK2 InhibitorsThe currently marketed JAK2 inhibitors include: Momelotinib DihydrochloridePacritinibFedratinib HydrochlorideUpadacitinibPeficitinib HydrobromideBaricitinibTofacitinib CitrateRuxolitinib PhosphateDeuterated RuxolitinibLestaurtinib For more information, please click on the image below. What are JAK2 inhibitors used for?JAK2 inhibitors are primarily used in the treatment of myeloproliferative neoplasms (MPNs) For more information, please click on the image below to log in and search. How to obtain the latest development progress of JAK2 inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of JAK2 inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

100 Deals associated with Lestaurtinib

External Link

KEGG	Wiki	ATC	Drug Bank
D04696	Lestaurtinib	-	DB06469

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Relapsing acute myeloid leukemia	Phase 3	Sweden	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Phase 3	Australia	Cephalon, Inc.	01 Oct 2003
Relapsing acute myeloid leukemia	Phase 3	Poland	Cephalon, Inc.	01 Oct 2003
Acute Lymphoblastic Leukemia	Phase 3	-	Cephalon, Inc.	-
Acute Lymphoblastic Leukemia	Phase 3	-	Kyowa Kirin Co., Ltd.	-
Acute Lymphoblastic Leukemia	Phase 2	Australia	-	-
Acute Lymphoblastic Leukemia	Phase 2	United States	-	-
Acute Lymphoblastic Leukemia	Phase 2	New Zealand	-	-
Acute Lymphoblastic Leukemia	Phase 2	Canada	-	-
Pancreatic Cancer	Phase 2	United States	Cephalon, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

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)	(uonkyjktgu) = gsurunatdk oqmkjwelpz (mwkptxkwxs, sigszbkggf - ltzlttvigv) 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)	(uonkyjktgu) = liungxqqib oqmkjwelpz (mwkptxkwxs, gmmdmooaof - bknldqpeey) View more	-	20 Dec 2013
NCT00494585 (CTgov)	Phase 2	Myelofibrosis \| Leukemia \| Primary Myelofibrosis	27	CEP-701	(qczsaafkrl) = iuxllhnsly cafclhvade (uqbkrnwzfd, pnbrllsbww - wopjpykyvz) View more	-	04 May 2011
ASCO2010	Phase 1	Refractory Neuroblastoma	47	Lestaurtinib	lsdfjhikqx(mqdgzrjxhq) = tdwgxcrhcq ymvsjulwvb (nvdahccfac )	-	20 May 2010

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