A Phase I Study of SF1126, a Dual PI3 Kinase and Bromodomain Inhibitor, in Combination With Nivolumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A-B7 Cirrhosis

Primary Objectives:
1. To determine the maximum tolerated dose (MTD) or maximum recommended dose of SF1126 in combination with nivolumab in adult patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.
2. To determine the recommended phase II dose of SF1126 in combination with nivolumab in patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.
Secondary Objectives:
1. To describe the safety and tolerability of SF1126 in adult patients with underlying liver disease by ongoing evaluation of adverse events.
2. To determine pharmacokinetics in HCC patients.
3. To assess the effect of SF1126 in combination with nivolumab on progression-free survival and overall survival.
Primary Endpoint:
The primary endpoint is the rate of dose limiting toxicities (DLTs) at within 56 days of starting treatment, and the maximum tolerated dose or maximum recommended dose of SF1126 in combination with nivolumab.
Secondary Endpoints:
1. Adverse events related to SF1126 (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness).
2. Pharmacokinetics in HCC patients.
3. The proportion of patients remaining progression-free by radiographic criteria as assessed by RESIST v1.1 at 4 months, and, as available, median progression-free survival and overall survival estimated using the Kaplan-Meier method.

开始日期2017-03-27

申办/合作机构

SignalRx Pharmaceuticals, Inc.

[+1]

NCT02644122

/ Terminated临床2期IIT

A Phase II Open Label Study of the PI3 Kinase (PI-3) Inhibitor, SF1126, in Patients With Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

The purpose of this study is to test the good and bad effects of an experimental drug called SF1126. This drug is being tested in patients whose cancer has not been controlled by available standard therapies and who have certain genes in their tumor.
SF1126 is a drug that inhibits a cell protein called phosphatidyl inositol 3 kinase (PI3K). PI3K is part of signaling pathway that tells cancer cells to grow, survive, invade and metastasize. PI3K also has an important role in the development of blood vessels that are required to support tumor growth. SF1126 is being developed by SignalRx Pharmaceuticals, Inc. It is considered an experimental drug because it is not approved by the FDA for any disease treatment.

开始日期2016-11-01

申办/合作机构

University of California San Diego

[+1]

NCT02337309

/ Terminated临床1期IIT

Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma

SF1126 is a novel inhibitor of PI3 kinase and mTOR that includes an active moiety (consisting of LY294002) linked to an RGDS tetrapeptide that targets the active agent to integrin expressing tissues. In this first pediatric phase 1 trial of SF1126, dose escalation will follow a 3+3 dose escalation design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 10 patients with tumors with MYCN amplification, Mycn expression, or Myc expression will be treated.
Funding Source - FDA OOPD

开始日期2015-07-09

申办/合作机构

SignalRx Pharmaceuticals, Inc.

[+1]

100 项与 SF-1126 相关的临床结果

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100 项与 SF-1126 相关的转化医学

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100 项与 SF-1126 相关的专利（医药）

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项与 SF-1126 相关的文献（医药）

2021-04-01·Journal of pediatric hematology/oncology4区 · 医学

Augmented Antitumor Activity for Novel Dual PI3K/BDR4 Inhibitors, SF2523 and SF1126 in Ewing Sarcoma

4区 · 医学

Article

作者: Goldin, Amanda N. ; Joshi, Shweta ; Singh, Alok ; Jamieson, Christina ; Durden, Donald L.

Ewing sarcoma (ES) is the second most common pediatric bone cancer. Despite recent advances in the treatment, patients with metastatic tumors have dismal prognosis and hence novel therapies are urgently needed to combat this cancer. A recent study has shown that phosphoinositide-3 kinase (PI3K) inhibitors can synergistically increase sensitivity to bromodomain and extraterminal domain inhibitors in ES cells and therefore combined inhibition of PI3K and bromodomain and extraterminal domain bromodomain proteins might provide benefit in this cancer. Herein, we have investigated the efficacy of dual PI3K/BRD4 inhibitors, SF2523 and SF1126, for their antitumor activity in ES cell lines. The effect of SF1126 and SF2523 on cell viability and PI3K signaling was assessed on a panel of human ES cell lines. To evaluate the antitumor activity of SF1126, A673 cells were injected intrafemorally into RAG-2−/− mice and treated with 50 mg/kg SF1126 6 days per week, for 30 days. Both SF1126 and SF2523 decreased cell survival and inhibited phosphorylation of AKT in human ES cell lines. In vivo, SF1126 showed a significant reduction in tumor volume. These results suggest that dual PI3K/BRD4 inhibitor, SF1126, has antitumor activity in ES models.

2020-06-04·ChemMedChem3区 · 医学

Discovery of Novel Autophagy Inhibitors and Their Sensitization Abilities for Vincristine‐Resistant Esophageal Cancer Cell Line Eca109/VCR

3区 · 医学

Article

作者: Guo, Chunling ; Li, Hongwei ; Hui, Wenqi ; Ouyang, Qin ; Peng, Ruikun ; Shan, Changyu ; Gu, Jing ; Chen, Yingchun ; Wang, Zheng

Abstract:

Resistance phenomena, especially acquired drug resistance, have been severely hampering the application of chemotherapeutics during cancer chemotherapy. Autophagy plays a role in maintaining the survival of cancer cells and might mediate resistance to chemotherapy drugs. Herein, a new series of 5‐amino‐2‐ether‐benzamide derivatives were synthesized and evaluated as autophagy inhibitors. Selected from 14 synthesized compounds as lead autophagy inhibitor, N‐(cyclohexylmethyl)‐5‐(((cyclohexylmethyl)amino)methyl)‐2‐((4‐(trifluoromethyl)benzyl)oxy)benzamide (4 d) showed the most obvious effect of LC3B protein conversion. Further, its autophagy inhibition, evaluated by using transmission electron microscopy and confocal microscopy, showed that the fusion of autophagosomes and lysosomes in the final stage of autophagic flux was suppressed. We also found that 4 d could enhance the chemosensitivity of vincristine in vincristine‐resistant esophageal cancer cell line Eca109/VCR in a synergistic, associative manner. Moreover, a computational study showed that 4 d might bind with p62‐zz to inhibit autophagy. We also found 4 d to be relatively less cytotoxic to normal cells versus cancer cells than the reported p62‐zz inhibitor.

2019-04-01·Asian Pacific journal of cancer prevention : APJCP

An In silico Approach to Identify High Affinity Small Molecule Targeting m-TOR Inhibitors for the Clinical Treatment of Breast Cancer

Article

作者: Sweta, Jajoriya ; Nayarisseri, Anuraj ; Panwar, Umesh ; Singh, Sanjeev Kumar ; Vuree, Sugunakar ; Patidar, Khushboo ; Sandhu, Manpreet Kaur

Breast cancer is the most frequent malignancy among women. It is a heterogeneous disease with different subtypes defined by its hormone receptor. A hormone receptor is mainly concerned with the progression of the PI3K/AKT/ mTOR pathway which is often dysregulated in breast cancer. This is a major signaling pathway that controls the activities such as cell growth, cell division, and cell proliferation. The present study aims to suppress mTOR protein by its various inhibitors and to select one with the highest binding affinity to the receptor protein. Out of 40 inhibitors of mTOR against breast cancer, SF1126 was identified to have the best docking score of -8.705, using Schrodinger Suite which was further subjected for high throughput screening to obtain best similar compound using Lipinski’s filters. The compound obtained after virtual screening, ID: ZINC85569445 is seen to have the highest affinity with the target protein mTOR. The same result based on the binding free energy analysis using MM-GBSA showed that the compound ZINC85569445 to have the the highest binding free energy. The next study of interaction between the ligand and receptor protein with the pharmacophore mapping showed the best conjugates, and the ZINC85569445 can be further studied for future benefits of treatment of breast cancer.

项与 SF-1126 相关的新闻（医药）

2021-04-30

·GlobeNewswire

Advanced Liver Cancer Drug Pipeline Prospers with an Inrush

Los Angeles, USA, April 29, 2021 (GLOBE NEWSWIRE) -- Advanced Liver Cancer Drug Pipeline Prospers with an Inrush of Pharma Companies and Emerging Novel Therapies A comprehensive analysis of 50+ key companies and 50+ emerging therapies enriching the Advanced Liver Cancer Pipeline Landscape. DelveInsight’s ‘Advanced Liver Cancer Pipeline Insights’ report provides a holistic view of the pipeline therapies that are under development in pre-clinical as well as clinical stages of development and growth prospects across the Advanced Liver Cancer domain. Some of the key highlights from the Advanced Liver Cancer pipeline report are: In the News Got queries? Want to know more? Request for Sample @ Advanced Liver Cancer Clinical Trial Analysis and Pipeline Insights Advanced Liver Cancer Pipeline Activity: At a Glance Reach out @ Advanced Liver Cancer Pipeline: Novel therapies and emerging technologies Advanced Liver Cancer Pipeline Agent Assessment The Advanced Liver Cancer Pipeline report lays down holistic coverage of active pipeline assets segmented by Stage, Product Type, Route of Administration, Molecule Type, Target, and Indications of various drugs. By Product Type By Stage By Molecule Type By Route of Administration By Mechanism of Action By Targets By Stage and Route of AdministrationBy Stage and Product Type For more information on emerging drugs, visit Advanced Liver Cancer Pipeline: Emerging Therapies and Trends Scope of the Report Coverage: GlobalKey Players: Siranomics, Novartis, Yiviva, Eisai, CAS Lamvac Biotech, Benhealth Biopharmaceutical, Chia Tai Tianqing Pharmaceutical, Surface Oncology, Zai Lab (Shanghai), Can-Fite Biopharma, Suzhou Zelgen Biopharmaceuticals, Innovent Biologics, SignalRX Pharmaceuticals, Carsgen Therapeutics, Shanghai Henlius Biotech, Jiangsu HengRui Medicine, Leap Therapeutics, Eureka Therapeutics, and many more.Key Advanced Liver Cancer Pipeline Therapies: STP 705, PDR001, YIV-906, H3B 6527, Plasmodium Immunotherapy, Activated CIK, AK105 Injection, SRF 388, MGD013, Namodenoson, SHR-1210, ET140203, PLM60, INC280, Donafenib, IBI308, SF1126, CAR-GPC3 T Cells, HLX10, and many more. Have a walkthrough of the report @ Advanced Liver Cancer Emerging Pipeline Key Questions Answered Need to clarify something? Get in touch @ Advanced Liver Cancer Drug Pipeline Insights Table of Contents Visit to know more of what’s covered @ Advanced Liver Cancer Emerging Therapies Other Insightful Reports Liver cancer IncidenceRead about the rising global burden of Liver Cancer. Excessive Daytime Sleepiness MarketGet a comprehensive analysis of epidemiology, pipeline therapies, and kye companies including Bioprojet Pharma/Harmony Biosciences, Axsome Therapeutics, Jazz Pharmaceuticals, BenevolentAI Bio, and many others. Bevacizumab Biosimilars InsightCoverage of about 40+ companies and 40+ marketed and pipeline drugs in Bevacizumab Biosimilars landscape. Pegfilgrastim Biosimilar InsightComprehensive insights about 20+ companies and 20+ marketed and pipeline drugs in Pegfilgrastim Biosimilars landscape. Different Types of Alternative MedicineKnow more about the state of Alternative Medicine in Healthcare and their changing landscape. Adeno-Associated Virus (AAV) Vectors in Gene TherapyAnalysis of emerging therapies and key companies including Pfizer (previously Sangamo Biosciences), NightstaRx Ltd, a Biogen Company, MeiraGTx, Neurocrine Biosciences/ Voyager Therapeutics, Roche (previously Spark Therapeutics)/Pfizer, Sangamo Therapeutics, Freeline Therapeutics, Spark Therapeutics, Asklepios Biopharmaceutical (Actus Therapeutics), Audentes Therapeutics, Roche/Sarepta Therapeutics, Horama S.A., MeiraGTx UK II Ltd, RegenxBio, Sangamo Therapeutics, Amicus Therapeutics, Amicus Therapeutics, and several others. Angelman Syndrome MedicationsA rich analysis of emerging drug therapies and key companies such as GeneTX Biotherapeutics, LLC, Ultragenyx Pharmaceutical Inc, Hoffmann-La Roche, Ovid Therapeutics Inc., Biogen, and others involved in the Angelman Syndrome market. Get in-depth knowledge of the healthcare and pharma world through DelveInsight's Competitive Intelligence Services and Business Solutions. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. For more insights, visit Pharma, Healthcare, and Biotech News

基因疗法生物类似药免疫疗法

100 项与 SF-1126 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05210

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性头颈部鳞状细胞癌	临床2期	美国	SignalRx Pharmaceuticals, Inc.	2016-11-01
晚期肝细胞癌	临床1期	美国	SignalRx Pharmaceuticals, Inc.	2017-03-27
转移性肝细胞癌	临床1期	美国	SignalRx Pharmaceuticals, Inc.	2017-03-27
难治性神经母细胞瘤	临床1期	美国	SignalRx Pharmaceuticals, Inc.	2015-07-09
晚期恶性实体瘤	临床1期	美国	SignalRx Pharmaceuticals, Inc.	2007-04-01
晚期恶性实体瘤	临床1期	美国	Semafore Pharmaceuticals, Inc.	2007-04-01
转移性肿瘤	临床1期	美国	Semafore Pharmaceuticals, Inc.	2007-04-01
转移性肿瘤	临床1期	美国	SignalRx Pharmaceuticals, Inc.	2007-04-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02644122 (CTgov)	临床2期	转移性头颈部鳞状细胞癌	1	SF1126	獵鑰選範艱積糧獵廠選 = 齋選蓋鹹願遞繭簾窪淵餘餘蓋淵製構窪壓夢觸 (顧構範醖壓繭淵簾簾淵, 積齋鏇壓糧艱鹹衊築遞 ~ 窪鬱築積淵繭選鹹淵築) 更多	-	2018-06-11
ASCO2011	临床1期	实体瘤 \| B细胞淋巴瘤	39	SF1126	窪獵糧鏇鬱顧範蓋鏇製(願製淵壓餘獵壓窪鏇顧) = 夢構糧顧艱鬱繭選鬱鹹顧製鹹鏇襯遞鑰夢餘願 (鑰襯鹹艱鬱憲繭廠膚襯 )	-	2011-05-20
ASCO2008	临床1期	实体瘤	10	SF1126	構窪廠獵網鏇衊廠鹽憲(獵憲構鏇鏇鹹顧鹽鹽廠) = 1 patient discontinued study because of an SAE 窪製構醖簾繭鬱廠選糧 (網衊觸蓋積鹽鹹蓋襯壓 ) 更多	-	2008-05-20