更新于：2024-11-01

ULK2

更新于：2024-11-01

基本信息

别名

ATG1B、KIAA0623、Serine/threonine-protein kinase ULK2

+ [6]

简介

Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.

关联

项与 ULK2 相关的药物

Inlexisertib

靶点

ULK1 x ULK2

作用机制

ULK1抑制剂 [+1]

在研机构

Deciphera Pharmaceuticals, Inc.

原研机构

Deciphera Pharmaceuticals, Inc.

在研适应症

胃肠道间质瘤 [+4]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

GLX-1546

靶点

ULK1 x ULK2

作用机制

ULK1抑制剂 [+1]

在研机构

星药科技（北京）有限公司

原研机构

星药科技（北京）有限公司

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

SBP-7455

靶点

ULK1 x ULK2

作用机制

ULK1抑制剂 [+1]

在研机构

Sanford Burnham Prebys Medical Discovery Institute

原研机构

Sanford Burnham Prebys Medical Discovery Institute

在研适应症

三阴性乳腺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 ULK2 相关的临床试验

NCT05957367 / Recruiting临床1/2期

A Master Protocol for the Multi-Cohort, Phase 1/2 Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies

This is a Phase 1/2, multicenter, open-label (unless otherwise specified in a combination-specific module) study of DCC-3116 in combination with anticancer therapies. Modules within the master protocol are defined according to different combinations of DCC-3116 with other anticancer agents.

开始日期2023-09-28

申办/合作机构

Deciphera Pharmaceuticals, Inc.

NCT04892017 / Recruiting临床1/2期

A Phase 1/2, First-in-Human Study of DCC-3116 as Monotherapy and in Combination With RAS/MAPK Pathway Inhibitors in Patients With Advanced or Metastatic Solid Tumors With RAS/MAPK Pathway Mutations

This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.

开始日期2021-06-15

申办/合作机构

Deciphera Pharmaceuticals, Inc.

100 项与 ULK2 相关的临床结果

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100 项与 ULK2 相关的转化医学

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0 项与 ULK2 相关的专利（医药）

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167

项与 ULK2 相关的文献（医药）

2024-11-01·Aquatic Toxicology

Nano-alumina induced developmental and neurobehavioral toxicity in the early life stage of zebrafish, associated with mTOR

Article

作者: He, Kaihong ; Wang, Yanhong ; Chen, Jianping ; Chen, Jin ; Zhang, Ping ; Zhang, Ling ; Guo, Xinyue ; Shang, Nan ; Niu, Qiao ; Zhang, Ying ; Zhang, Qinli

The study aims to investigate the effects of nano-alumina (AlNPs) on the early development and neurobehavior of zebrafish and the role of mTOR in this process. After embryos and grown-up larvae exposed to AlNPs from 0 to 200 μg/mL, we examined the development, neurobehavior, AlNPs content, and mTOR pathway genes. Moreover, embryos were randomly administered with control, negative control, mTOR knockdown, AlNPs, and mTOR knockdown + AlNPs, then examined for development, neurobehavior, oxidative stress, neurotransmitters, and development genes. As AlNPs increased, swimming speed and distance initially increased and then decreased; thigmotaxis and panic-avoidance reflex substantially decreased in the high-dose AlNPs group; aluminum and nanoparticles considerably accumulated in the 100 μg/mL AlNPs group; AlNPs at high dose decreased mTOR gene and protein levels, stimulating autophagy via increasing ULK1 and ULK2. mTOR knockdown exacerbated the harm to normal development rate, eye and body length, and neurobehavior induced by AlNPs through raising ROS, SOD, and ACH levels but decreasing AchE activity and development genes. Therefore, AlNPs suppress neurobehavior through downregulating mTOR, and mTOR knockdown further aggravates their early development and neurobehavior loss, suggesting mTOR could be a potential target for the toxicity of AlNPs.

2024-10-01·Poultry Science

Gene coexpression network analysis reveals the genes and pathways in pectoralis major muscle and liver associated with wooden breast in broilers

Article

作者: Liu, Yuan ; Zhang, Runxiang ; Qin, Ziwen ; Han, Wenpeng ; Yuan, Hui ; Lu, Jun ; Liu, Shengnan

Wooden breast (WB) is a myopathy mainly affecting pectoralis major (PM) muscle in modern commercial broiler chickens, causing enormous economic losses in the poultry industry. Recent studies have observed hepatic and PM muscle injury in broilers affected by WB, but the relationships between WB and the 2 tissues are mostly unclear. In the current study, the RNA-seq raw data of PM muscle and liver were downloaded from GSE144000, and we constructed the gene coexpression networks of PM muscle and liver to explore the relationships between WB and the 2 tissues using the weighted gene coexpression network analysis (WGCNA) method. Six and 2 gene coexpression modules were significantly correlated with WB in the PM muscle and liver networks, respectively. TGF-beta signaling, Toll-like receptor signaling and mTOR signaling pathways were significantly enriched in the genes within the 6 gene modules of PM muscle network. Meanwhile, mTOR signaling pathway was significantly enriched in the genes within the 2 gene modules of liver network. In the consensus gene coexpression network across the 2 tissues, salmon module (r = -0.5 and p = 0.05) was significantly negatively correlated with WB, in which Toll-like receptor signaling, apoptosis, and autophagy pathways were significantly enriched. The genes related with the 3 pathways, myeloid differentiation primary response 88 (MYD88), interferon regulatory factor 7 (IRF7), mitogen-activated protein kinase 14 (MAPK14), FBJ murine osteosarcoma viral oncogene homolog (FOS), jun proto-oncogene (JUN), caspase-10, unc-51 like autophagy activating kinase 2 (ULK2) and serine/threonine kinase 11 (LKB1), were identified in salmon module. In this current study, we found that the signaling pathways related with cell inflammation, apoptosis and autophagy might influence WB across 2 tissues in broilers.

2024-08-02·Future Medicinal Chemistry

A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer

Article

作者: Wai, Lam Kok ; Fasihi Mohd Aluwi, Mohd Fadhlizil ; Leong, Sze-Wei ; Ilowefah, Muna Abdulsalam ; Rungrotmongkol, Thanyada ; Mohd Faudzi, Siti Munirah ; Alshwyeh, Hussah Abdullah ; Islami, Deri ; Alosaimi, Areej A ; Mediani, Ahmed ; Haris, Muhammad Salahuddin ; Taher, Muhammad ; Chia, Suet Lin ; Koeberle, Andreas ; Shamsudin, Nur Farisya ; Rullah, Kamal ; Suriya, Utid

Aim: Chromones are promising for anticancer drug development.Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC₅₀ 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC₅₀ 4.2 μM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1.Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs.

项与 ULK2 相关的新闻（医药）

2024-04-29

·Firstwordpharma

Ono to expand oncology pipeline with $2.4B Deciphera purchase

Ono Pharmaceutical agreed to acquire Deciphera Pharmaceuticals for $25.60 per share in cash, representing a total equity value of $2.4 billion, bolstering the Japanese firm’s oncology portfolio. Deciphera’s sole marketed product is the KIT inhibitor Qinlock (ripretinib), whilst its pipeline includes the CSF1R inhibitor vimseltinib and the ULK inhibitor DCC-3116.Gyo Sagara, chief executive of Ono, said “we expect that this acquisition…will not only expand Ono's target oncology portfolio, but also accelerate Ono's business development in the [US] and Europe, and strengthen kinase drug discovery research.”Qinlock is approved in the US, EU and more than 40 markets as a fourth-line treatment for gastrointestinal stromal tumours (GIST). However, efforts to expand its use in earlier settings fell flat in 2021 when the drug failed to significantly prolong progression-free survival (PFS) in the Phase III INTRIGUE study against Pfizer's Sutent (sunitinib) in patients with second-line GIST.Deciphera is currently investigating Qinlock in the late-stage INSIGHT trial for second-line GIST patients with mutations in KIT exon 11 and 17 and/or 18 and the absence of mutations in KIT exon 9, 13, and/or 14. Meanwhile, vimseltinib is expected to be filed with regulators later this year after meeting the primary endpoint of the Phase III MOTION study in patients with tenosynovial giant cell tumours not amenable to surgery.The boards of both companies have unanimously approved the transaction, which is expected to close in the third quarter. The price of the deal represents a premium of 74.7% over Deciphera’s closing share price on April 26.

临床3期并购上市批准