1、研究机构:Laminar Pharma、Avalo Therapeutics、NeuroFix therapeutics、Praxis Pharmaceutical、Lipopharma Therapeutics
2、别名:2-OHOA、2-Hydroxyoleic Acid Sodium、NFX-88、LAM-561A1、Idroxioleic acid
3、靶点:SMS1
4、剂型及给药途径:普通片剂; 口服给药;干混悬剂; 口服给药
5、结构式
6、适应症及进展
适应症
进展
最新进展日期
神经病理性疼痛
II期
2024-06-19
胶质母细胞瘤
III期
2025-03-05
7、研究期间发表论文
标题
内容类型
适应症
企业
技术平台
来源
发表日期
Incorporation of the antitumor compound 2OHOA and its metabolite into cell membranes
药理研究
胶质母细胞瘤
Laminar Pharma
2024 AACR
2024-04-09
2OHOA-mediated furin inhibition: Disrupting Notch via processing, transcription, and ADAM downregulation
药理研究
胶质母细胞瘤
Laminar Pharma
2024 AACR
2024-04-07
8、专利布局
公开(公告)号
专利主题
发明名称
申请日
法律状态
CN102356057A
化合物
多不饱和脂肪酸的衍生物作为药物的用途
2010-03-15
驳回
CN109999018A
化合物
多不饱和脂肪酸的衍生物作为药物的用途
2010-03-15
驳回
CN106420686B
化合物
多不饱和脂肪酸的衍生物作为药物的用途
2010-03-15
CN106349058B
化合物
多不饱和脂肪酸的衍生物作为药物的用途
2010-03-15
9、临床试验
登记号
试验标题
试验药
适应症
原始适应症
申办/合作机构
试验状态
试验分期
开始日期
完成日期
国家/地区
NCT04299191
Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors
Idroxioleic Acid
晚期恶性实体瘤 | 高级别胶质瘤
High-grade Glioma | Solid Tumor, Unspecified, Child
Laminar Pharmaceuticals SA (Spain) | Dana-Farber Cancer Institute, Inc. | Ocean Medical Center Association, Inc.
Recruiting
临床1/2期
2020-09-01
2026-12-01
美国
NCT04250922
A Randomized, Double-blind, Placebo-controlled Adjuvant Trial in Newly Diagnosed Primary Glioblastoma Subjects to Assess the Efficacy and Safety of LAM561 in Combination With Radiotherapy and Temozolomide Standard of Care Treatment.
替莫唑胺 (口服) | Idroxioleic Acid (口服)
多形性胶质母细胞瘤
Primary Glioblastoma | Glioblastoma Multiforme
Laminar Pharmaceuticals SA (Spain) | Laboratory Corporation of America Holdings | Theradis pharma
Active, not recruiting
临床2/3期
2019-12-01
2026-11-30
英国 | 意大利 | 以色列 | 法国 | 西班牙
NCT04148573
Randomized, Double-blind, Placebo Controlled, Parallel, Multicentric, Phase IIa Clinical Trial to Evaluate Safety, Tolerability, Therapeutic Efficacy of Daily Oral Treatment NFX88 on Neuropathic Pain in Patients With Spinal Cord Injury
Idroxioleic Acid
脊髓损伤 | 神经痛
Neuropathic Pain | Spinal Cord Injuries
Neurofix SL
Completed
临床2期
2019-10-01
2022-07-20
西班牙
NCT03867123
A Phase 1B Study of the Safety of LAM561 Administered Orally in Combination With Temozolomide (TMZ) and Radiation Therapy or With TMZ Alone in the First Line Treatment of Subjects With Glioblastoma
替莫唑胺 | Idroxioleic Acid
多形性胶质母细胞瘤 | 胶质母细胞瘤
Glioblastoma (GBM)
Laminar Pharmaceuticals SA (Spain)
Completed
临床1期
2018-12-04
2020-07-01
西班牙
NCT01792310
A Phase 1/2A Dose Escalation Study of LAM561 in Adult Patients With Advanced Solid Tumours Including Malignant Glioma
Idroxioleic Acid
晚期恶性实体瘤 | 胶质瘤
Glioma | Other Solid Tumours
Laminar Pharmaceuticals SA (Spain) | Vall d'Hebron Institut d'Oncologia | Specialized Medical Services-Oncology BV | Royal Marsden NHS Foundation Trust
Completed
临床1/2期
2013-05-01
2016-09-01
英国 | 西班牙
10、临床结果
标题
登记号
来源
分期
适应症
评价人数
用药方案
结果
评价
发布日期
申办/合作机构
来源链接
Synapse链接
Laminar Pharma Announces first open-label Progression-Free Survival data for LAM561 in combination with standard of Care in First-Line Therapy for Newly Diagnosed Glioblastoma MGMT-methylated patients
NCT04250922
PRNewswire
临床2/3期
胶质母细胞瘤
144
LAM561+radiotherapy + temozolomide
mPFS = 86.4 Week
积极
2025-03-05
Laminar Pharmaceuticals SA (Spain) | Laboratory Corporation of America Holdings | Theradis pharma
https://www.prnewswire.com/news-releases/laminar-pharma-announces-first-open-label-progression-free-survival-data-for-lam561-in-combination-with-standard-of-care-in-first-line-therapy-for-newly-diagnosed-glioblastoma-mgmt-methylated-patients-302393021.html
https://synapse.zhihuiya.com/clinical-result-detail/e95329d2dd88a855520850459aa23a55
Laminar Pharma Announces first open-label Progression-Free Survival data for LAM561 in combination with standard of Care in First-Line Therapy for Newly Diagnosed Glioblastoma MGMT-methylated patients
NCT04250922
PRNewswire
临床2/3期
胶质母细胞瘤
144
placebo + radiotherapy + temozolomide
mPFS = 54 ~ 7 Week
积极
2025-03-05
Laminar Pharmaceuticals SA (Spain) | Laboratory Corporation of America Holdings | Theradis pharma
https://www.prnewswire.com/news-releases/laminar-pharma-announces-first-open-label-progression-free-survival-data-for-lam561-in-combination-with-standard-of-care-in-first-line-therapy-for-newly-diagnosed-glioblastoma-mgmt-methylated-patients-302393021.html
https://synapse.zhihuiya.com/clinical-result-detail/e95329d2dd88a855520850459aa23a55
Final report of a phase I study of 2-hydroxyoleic acid (2OHOA) a novel sphingomyelin synthase activator in patients (pt) with advanced solid tumors (AST) including recurrent high grade gliomas (rHGG).
NCT01792310
ASCO
临床1期
HR阳性/HER2低表达实体瘤 | 复发性恶性胶质瘤
54
2-hydroxyoleic acid
TRAE(grade 1/2) = diarrhea (n = 13;11pt),nausea (n = 7;6pt), ALT increase (n = 6;4pt), pruritus in throat (4pt), fatigue (4pt) and vomiting (3pt)
积极
2017-06-05
Laminar Pharmaceuticals SA (Spain) | Vall d'Hebron Institut d'Oncologia | Specialized Medical Services-Oncology BV | Royal Marsden NHS Foundation Trust
https://ascopubs.org/doi/abs/10.1200/jco.2017.35.15_suppl.2554 | https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.2554
https://synapse.zhihuiya.com/clinical-result-detail/a4a55de8220d45520ee8085329534a08
A phase I study of 2-hydroxyoleic acid (2-OHOA), a novel sphingomyelin synthase activator in patients (pt) with advanced solid tumors (AST) including refractory high grade gliomas/glioblastomas (GBM): Updated results of the expansion.
NCT01792310
ASCO
临床1期
胶质母细胞瘤 | HR阳性/HER2低表达实体瘤
14
2-OHOA
Adverse Event: Adverse events (AE) = Toxicities are manageable, with no safety concerns thus far in any patients
-
2016-05-20
Laminar Pharmaceuticals SA (Spain) | Vall d'Hebron Institut d'Oncologia | Specialized Medical Services-Oncology BV | Royal Marsden NHS Foundation Trust
https://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.e14086
https://synapse.zhihuiya.com/clinical-result-detail/2d582289e202a2522a28d25558d58e35
11、转化医学
研究
亮点
主题
期刊/会议
出版日期
适应症
机构
Targeting the Notch-Furin axis with 2-hydroxyoleic acid: a key mechanism in glioblastoma therapy
-
药物发现/临床前
Cell Oncol (Dordr)
2024-10-14
多形性胶质母细胞瘤
University of The Balearic Islands | Laminar Pharmaceuticals
Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury
-
2期临床研究
Spinal Cord
2024-06-19
神经痛
Hospital Universitario Virgen de Las Nieves | Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain. | Universidad Islas Baleares, Palma, Islas Baleares, Spain.
Abstract 4729: Incorporation of the antitumor compound 2OHOA and its metabolite into cell membranes
本研究旨在探讨抗肿瘤化合物2OHOA及其代谢产物在细胞膜中的作用机制。我们发现2OHOA主要被胶质母细胞瘤细胞膜所吸收,而在非肿瘤细胞中吸收较少,这解释了其在胶质母细胞瘤治疗中的特异性效果和低副作用。此外,我们观察到2OHOA代谢产物C17:1n-9通过α-氧化途径代谢,对胶质母细胞瘤细胞生长产生抑制作用,增强了2OHOA的活性。最后,我们将这一代谢产物作为生物标志物,用于预测和追踪2OHOA治疗的药代动力学。总之,2OHOA在肿瘤细胞和非肿瘤细胞的细胞膜中的吸收存在差异,而2OHOA及其代谢产物C17:1n-9均具有抗增殖作用,对于治疗难以有效治疗的胶质母细胞瘤患者具有潜在的吸引力。
2/3期临床研究
AACR 2024
2024-03-22
多形性胶质母细胞瘤
Laminar Pharma, Inc., Palma de Mallorca, Spain;
Abstract 517: 2OHOA-mediated furin inhibition: Disrupting Notch via processing, transcription, and ADAM downregulation
本研究评估了2-羟基油酸(2OHOA)对胶质母细胞瘤(GBM)细胞的影响,发现2OHOA通过抑制Notch信号通路来发挥抗肿瘤作用。具体来说,2OHOA通过两种方式抑制Notch3和Notch2信号通路,分别是通过抑制转录和通过与furin的物理结合来阻断第一次切割。此外,2OHOA还降低了Notch的第二次切割,因为ADAM10是furin的底物。这些发现揭示了2OHOA在治疗GBM中的新型分子靶点,为其在生物医药领域的潜在应用提供了新思路。
2/3期临床研究
AACR 2024
2024-03-22
胶质母细胞瘤
Laminar Pharma, Inc., Palma de Mallorca, Spain;
A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma.
该研究报告了一项多中心的第一阶段/2A阶段试验,评估了首个脑透过性合成羟基化脂质——羟基油酸(2-OHOA)在胶质瘤和其他晚期实体肿瘤患者中的安全性、耐受性、药代动力学和抗肿瘤活性。研究结果显示,2-OHOA在患者中的吸收迅速且剂量成比例。治疗总体上耐受良好,最常见的治疗相关不良事件为可逆的1-2级恶心、呕吐和腹泻。在高级别胶质瘤患者中观察到潜在的活性,其中24%的患者在临床上获益。因此,2-OHOA在治疗胶质瘤和其他实体肿瘤恶性肿瘤方面具有潜在的候选价值。
1/2期临床研究
Pubmed
2023-09-01
胶质瘤
Northern Centre for Cancer Care | Laminar Pharmaceuticals | The Royal Marsden Hospital and the Institute of Cancer Research
Abstract 4869: Furin and Notch signaling pathway as part of the 2OHOA landscape against glioblastoma
本研究探讨了2-羟基油酸(2OHOA)在治疗胶质母细胞瘤(GBM)中的作用机制。研究发现,2OHOA通过改变癌细胞的脂质组成和结构,增加膜流动性,抑制膜相关蛋白的活性,从而抑制增殖,诱导内质网应激和分化,并最终通过自噬触发细胞死亡。此外,研究还发现2OHOA通过直接抑制furin酶的活性,下调Notch信号通路,从而发挥抗肿瘤作用。这些发现为2OHOA在GBM和其他病理治疗中作为新靶点的应用提供了重要依据。
3期临床研究
AACR 2023
2023-04-04
胶质母细胞瘤
Laminar Pharmaceuticals SA (Spain)
CADD-10. 2-HYDROXYOLEIC ACID, A NOVEL MEMBRANE LIPID REGULATOR, DEMONSTRATES CLINICAL ACTIVITY IN HIGH-GRADE GLIOMA
2-羟基油酸(2OHOA)是一种新型的膜脂调节剂,是第一种可能通过改变细胞膜脂质含量来发挥抗癌作用的药物。2OHOA通过其独特的机制,靶向癌细胞的膜脂质组成和结构,改变下游信号级联,抑制肿瘤细胞增殖。欧洲对2OHOA在成人高级别胶质瘤和其他晚期实体肿瘤患者的I/IIa期试验结果令人鼓舞,五名难治性恶性胶质瘤患者根据RANO标准表现出六个月或更长时间的客观临床益处,其中一个胶质母细胞瘤患者的原发病灶持续部分缓解超过33个月。该药物在成人患者中耐受性良好,毒性小。欧洲正在筹划将2OHOA与标准治疗(放疗和替莫唑胺)联合用于新诊断的成人高级别胶质瘤的IIb期试验。美国将于2018年开展2OHOA用于儿童高级别胶质瘤和其他晚期实体肿瘤的I期试验。
1/2期临床研究
SNO 2018
2018-11-05
高级别胶质瘤
Hackensack University Medical Center, Hackensack, NJ, USA
Final report of a phase I study of 2-hydroxyoleic acid (2OHOA) a novel sphingomyelin synthase activator in patients (pt) with advanced solid tumors (AST) including recurrent high grade gliomas (rHGG).
该研究报告总结了2-羟基油酸(2OHOA)在晚期实体肿瘤患者中的临床试验结果。2OHOA是一种口服可用的合成羟基脂肪酸,能激活SGMS1并调节癌细胞膜的脂质含量,从而影响关键信号蛋白在细胞膜的定位,导致Ras/MAPK、PI3K/Akt和PKC/cyclin/CDK信号通路的失活。研究包括了剂量递增和部分扩展队列,共有54名患者参与,结果显示2OHOA在P2RD的4000mg TID口服剂量下耐受良好,并且在重复治疗后已经达到稳态。部分患者出现了持续的肿瘤缓解和稳定病情,表现出潜在的抗肿瘤活性。这些初步结果表明2OHOA在治疗重复治疗的高级别胶质母细胞瘤患者方面具有潜在的临床价值,值得进一步进行第二阶段研究。
1期临床研究
ASCO 2017
2017-05-30
-
Northern Centre for Cancer Care | Onkologikoa | Vall d'Hebron University Hospital | Lipopharma Therapeutics SL | SMS-Oncology, Amsterdam, Netherlands
Abstract CT067: 2-hydroxyoleic acid (2-OHOA), a novel activator of sphingomyelin synthase with antitumor activity in refractory glioblastoma: results of the first-in-human dose-escalation (DE) study in patients with advanced solid tumors (AST) and refractory gliomas/glioblastomas
本研究旨在评估2-羟基油酸(2-OHOA)在晚期实体肿瘤和难治性胶质瘤/胶质母细胞瘤患者中的安全性、耐受性和推荐的2期剂量(RP2D),以及其药代动力学(PK)、药效动力学(PD)和抗肿瘤特性。研究结果显示,2-OHOA的MTD和RP2D为每日12g,对一些难治性胶质母细胞瘤患者产生了持久的临床益处。招募仍在进行中,包括针对晚期胶质瘤/胶质母细胞瘤的扩展队列。Clinical trial information: NCT01792310。
1/2期临床研究
AACR 2016
2016-07-15
胶质母细胞瘤
Lipopharma, Spain | Institute of Cancer Research, London, United Kingdom
A phase I study of 2-hydroxyoleic acid (2-OHOA), a novel sphingomyelin synthase activator in patients (pt) with advanced solid tumors (AST) including refractory high grade gliomas/glioblastomas (GBM): Updated results of the expansion.
该研究对2-羟基油酸(2-OHOA)在晚期实体肿瘤(AST)患者中的疗效进行了更新。2-OHOA是一种新型合成羟基化脂质,能激活SGSM1并调节癌细胞膜的脂质含量,已在包括高级别胶质瘤/胶质母细胞瘤(GBM)在内的多种移植裸鼠模型中减小肿瘤生长。该药物穿过血脑屏障,对GBM预期的有效性也得到证实。12g/天的剂量对GBM患者安全可控,并出现药物反应。若进一步的研究结果表明安全性和耐受性无问题,12g/天将成为建议剂量。
1期临床研究
ASCO 2016
2016-05-20
胶质母细胞瘤 | HR阳性/HER2低表达实体瘤
Laminar Pharmaceuticals SA (Spain)
A first-in-human dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of oral 2-hydroxyoleic acid (2-OHOA) in adult patients (pt) with advanced solid tumors including grade III/IV glioblastoma multiforme (GBM).
本研究是关于口服2-羟基油酸(2-OHOA)在成年患有晚期实体瘤和III/IV级胶质母细胞瘤(GBM)的患者中的安全性、药代动力学(PK)和药效动力学(PD)的首次人体剂量递增研究。研究结果显示,2-OHOA可安全地给予患者,剂量可递增至4000mg BID。部分患者出现临床益处,包括1例GBM患者出现部分缓解。该研究仍在进行剂量递增,以确定推荐的2期剂量(RP2D),随后将扩大RP2D范围,包括实体瘤和III/IV级GBM患者。Clinical trial information: NCT01792310。
1/2期临床研究
ASCO 2015
2015-05-20
-
SMS-Oncology BU, Amsterdam, Netherlands | The Institute of Cancer Research and The Royal Marsden, London, United Kingdom
Oral 2‐hydroxyoleic acid inhibits reflex hypersensitivity and open–field‐induced anxiety after spared nerve injury
该研究评估了2-羟基油酸(2-OHOA)在周围神经病理性疼痛中的抗痛作用。结果显示,2-OHOA能显著减轻神经损伤后的机械和热敏感性,降低脊髓背角微胶质细胞的活化,并减少炎症介质COX-2/COX-1比值。此外,2-OHOA还能恢复受损大鼠的行为表现,减轻焦虑情绪。因此,2-OHOA可能通过抑制脊髓背角微胶质细胞活化介导抗痛作用。
药物发现/临床前
Pubmed
2015-01-01
-
SESCAM Hospital Nacional de Parapléjicos
Microarray gene analysis of rat spinal cord tissue treated with human albumin and 2-hydroxy oleic acid
-
药物发现/临床前
SFN 2013
2013-11-12
脊髓损伤
Univ. of the Balearic Islands | Hosp Nacional de Paraplejicos
2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy
2-羟基油酸(2OHOA)是一种无毒的膜结合抗癌药物,能诱导胶质瘤细胞分化和自噬。与当前用于治疗胶质瘤的参考药物替莫唑胺(TMZ)相比,2OHOA更有效地对抗胶质瘤,并且不会出现肿瘤复发。2OHOA的新作用机制与膜脂组成的重要变化有关,主要是磷脂鞘氨醇(SM)水平的恢复。与膜脂调节并行,2OHOA治疗诱导Ras从膜转移到细胞质,抑制了MAP激酶途径,减少了PI3K/Akt途径的活性,并下调了Cyclin D-CDK4/6蛋白,随后使视网膜母细胞瘤蛋白(RB)低磷酸化。这些调节效应与胶质瘤细胞分化为成熟胶质细胞并随后发生自噬性细胞死亡相关。由于其高效性、低毒性、口服易、以及对大脑的良好分布,2OHOA对于胶质瘤患者来说是一种新的、潜在有价值的治疗工具。
药物发现/临床前
Proc Natl Acad Sci U S A
2012-05-14
胶质瘤
Tianjin Medical Laboratory | Institut Universitari d’Investigacions en Ciències de la Salut
Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy
-
药物发现/临床前
Proc Natl Acad Sci U S A
2011-11-21
肿瘤
University of The Balearic Islands