预约演示

更新于：2025-01-23

PANK2

更新于：2025-01-23

基本信息

别名

C20orf48、FLJ11729、HARP

+ [12]

简介

Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150). Required for angiogenic activity of umbilical vein of endothelial cells (HUVEC) (PubMed:30221726). Cytoplasmic isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.

关联

项与 PANK2 相关的药物

Claziprotamide

靶点

PANK1 x PANK2

作用机制

PANK2 agonists [+1]

在研机构-

原研机构

CoA Therapeutics, Inc.初创企业

在研适应症

泛酸激酶相关神经变性

非在研适应症

有机酸血症 [+2]

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 PANK2 相关的临床试验

NCT04836494

/ Terminated临床1期

A First-in-human, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Escalation to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BBP-671 in Healthy Subjects and In Patients With Propionic Acidemia or Methylmalonic Acidemia

The purpose of this study is to assess the safety, tolerability, PK and PD of BBP-671 in healthy volunteers and patients with Propionic Acidemia or Methylmalonic Acidemia.

开始日期2021-03-25

申办/合作机构

CoA Therapeutics, Inc.初创企业

100 项与 PANK2 相关的临床结果

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100 项与 PANK2 相关的转化医学

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0 项与 PANK2 相关的专利（医药）

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360

项与 PANK2 相关的文献（医药）

2025-01-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA)

Article

作者: Cudna, Agnieszka ; Wydrych, Agata ; Wieckowski, Mariusz R ; Pierzynowska, Karolina ; Jakubek-Olszewska, Patrycja ; Pinton, Paolo ; Węgrzyn, Grzegorz ; Janikiewicz, Justyna ; Rydzewski, Marcel ; Cwyl, Maciej ; Lebiedzińska-Arciszewska, Magdalena ; Cyske, Zuzanna ; Skowrońska, Marta ; Dobrzyń, Agnieszka ; Kurkowska-Jastrzębska, Iwona ; Pakuła, Barbara ; Koopman, Werner J H ; Rintz, Estera ; Dobosz, Aneta M ; Gaffke, Lidia

Mutations in the following genes: PANK2, PLA2G6, C19orf12, WDR45, CP, FA2H, ATP13A2, FTL, DCAF17, and CoASY are associated with the development of different subtypes of inherited rare disease Neurodegeneration with Brain Iron Accumulation (NBIA). Additionally, recently described mutations in FTH1, AP4M1, REPS1, SCP2, CRAT and GTPBP2 affecting iron and lipid metabolism also are thought to be involved in NBIA development. Four main subtypes, pantothenate kinase-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), mitochondrial membrane protein-associated neurodegeneration (MPAN) and beta-propeller protein-associated neurodegeneration (BPAN), are responsible for up to 82 % of all NBIA cases. Here we studied fibroblasts from 11 patients with pathogenic mutations in C19orf12, and demonstrate various cellular aberrations. Differences between fibroblasts from healthy individuals and MPAN patients were potentiated when cells were grown under oxidative phosphorylation (OXPHOS) promoting condition suggesting an impaired metabolic flexibility. The extent of some of the cellular aberrations quantitatively correlated with disease severity, suggesting their involvement in the NBIA pathomechanism.

2024-12-07·Biological and Pharmaceutical Bulletin

Exploration of Novel Metabolic Features Reflecting Statin Sensitivity in Lung Cancer Cells

Article

作者: Warita, Tomoko ; Tashiro, Jiro ; Warita, Katsuhiko ; Ishikawa, Takuro ; Sugiura, Akihiro ; Mizoguchi, Kana

Statins are cholesterol-lowering drugs often used for the treatment of dyslipidemia. Statins also exert anti-cancer effects by inhibiting hydroxymethylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis. We previously reported that the susceptibility to statin treatment differs among cancer cells and that functional E-cadherin expression on the plasma membrane could be a biomarker of statin sensitivity in cancer cells. However, the detailed qualitative and molecular differences between statin-sensitive and statin-resistant cancer cells remain unclear. Here, we explored novel parameters related to statin sensitivity by comparing gene expression profiles and metabolite contents between statin-sensitive and statin-resistant lung cancer cell lines. We found that the expression of most cholesterol synthesis genes was lower in the statin-sensitive cancer cell line, HOP-92, than in the statin-resistant cancer cell line, NCI-H322M. Moreover, HOP-92 cells originally exhibited lower levels of CoA and HMG-CoA. Additionally, atorvastatin decreased the mRNA expression of PANK2, a rate-limiting enzyme in CoA synthesis. Atorvastatin also reduced the mRNA levels of the cholesterol esterification enzyme SOAT1, which was consistent with a decrease in the ratio of cholesterol ester to total cholesterol in HOP-92 cells. Our data suggest that the cholesterol synthetic flow and CoA content may be limited in statin-sensitive cancer cells. We also suggest that CoA synthesis and cholesterol storage may fluctuate with atorvastatin treatment in statin-sensitive cancer cells.

2024-10-17·Tremor and Other Hyperkinetic Movements

Patient Selection for Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

Article

作者: Hilliard, Justin D ; Wong, Joshua K ; Hogarth, Penelope ; Chan, Jason L ; Rawls, Ashley E ; Okun, Michael S

Clinical VignetteA 23-year-old woman with pantothenate kinase-associated neurodegeneration (PKAN) presented with medication-refractory generalized dystonia and an associated gait impairment.Clinical DilemmaBilateral globus pallidus internus (GPi) deep brain stimulation (DBS) can be an effective treatment for dystonia. However, outcomes for PKAN DBS have been variable and there are no standardized criteria for patient selection.Clinical SolutionBilateral GPi DBS implantation resulted in improvement in dystonia and gait. The benefit has persisted over one year after implantation.Gap in KnowledgePKAN is a rare neurodegenerative disorder and evidence supporting the use of PKAN DBS has been largely limited to case reports and case series. Consequently, there is a paucity of long-term data, especially on gait-related outcomes.Expert CommentaryThe clinical characteristics of dystonia that respond to DBS tend to respond in PKAN. Clinicians counselling patients about the effects of DBS for PKAN should thoughtfully discuss gait and postural instability as important aspects to consider, especially as the disease will progress post-DBS.

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