(SB-247464) - 药物靶点：CSF-3R x M-CSF_专利_临床

概要

基本信息

药物类型

小分子化药

别名

G-CSF mimic (Ligand)

靶点

CSF-3R x M-CSF

作用机制

CSF-3R激动剂(巨噬细胞集落刺激因子3受体激动剂)、M-CSF激动剂(巨噬细胞集落刺激因子-1激动剂)

治疗领域

感染血液及淋巴系统疾病

在研适应症-

非在研适应症

感染白细胞减少

原研机构

Ligand Pharmaceuticals, Inc.

在研机构-

非在研机构

GlaxoSmithKline LLC

Ligand Pharmaceuticals, Inc.

最高研发阶段无进展药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C28H22N12

InChIKeyDHYXCTSDXUOXGE-HNRBIFIRSA-N

CAS号212077-57-1

关联

26

项与 SB-247464 相关的临床试验

NCT04112589 / Active, not recruiting临床1/2期IIT

A Multicenter, Prospective, Non-randomized, Phase I-II Trial to Assess the Efficacy and Safety of the Combination of Oral Quizartinib and the FLAG-IDA Chemotherapy Regimen in First Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients

This is a multicenter, prospective, non-randomized, Phase I-II trial to assess the efficacy and safety of the combination of oral quizartinib and FLAG-IDA chemotherapy schedule (FLAG-QUIDA regimen) in first relapsed/refractory AML (acute myeloid leukemia) patients.

开始日期2019-12-26

申办/合作机构

Syntax for Science, S.L

[+1]

NCT03045627 / Unknown status临床2期IIT

A Multi-center Randomized Open-label Clinical Trial of Ara-C, Aclarubicin Combined With PEG-G-CSF for Initial Treatment of Acute Myeloid Leukemia Patients

Most of patients with acute myeloid leukemia (AML) are elder and have poor prognosis despite induction chemotherapy.The regimen of cytarabine(Ara-C), aclarubicin and G-CSF (CAG regimen ) has been widely used in China for the treatment of acute myeloid leukemia (AML). Strategies to reduce the toxicity associated with intensive chemotherapy include the attenuated doses of standard regimens and myeloid growth factors. Granulocyte colony-stimulating factor(G-CSF) is efective in the prophylaxis and management of chemotherapy-induced neutropenia，but requires daily administration because of its short half-life． Pegylated granulocyte colony-stimulating factor (PEG-G-CSF )is a long-acting reagent that permits less frequent injection．The project is undertaken by Qilu Hospital of Shandong University and other well-known hospitals in China.In order to report the efficacy and safety of PEG-G-CSF combined with Ara-C and aclarubicin for the treatment of Acute Myeloid Leukemia, compared to the regimen of Ara-C, aclarubicin and G-CSF (CAG ).

开始日期2017-01-01

申办/合作机构

山东大学

NCT02866331 / Unknown status临床2期IIT

Phase II, Randomized, Double-blind Clinical Trial for Efficacy of G-CSF and Autologous Cord Blood Infusion in Children With Cerebral Palsy

This study is performed to reveal the safety and feasibility of combination therapy with autologous cord blood mononuclear cells (CB) and G-CSF as well as repeated administration of G-CSF for children with cerebral palsy. The evaluation tools are as follows: (1) Developmental tests (DDST, PEDI, GMFM, GMFCS, MACS, QUEST), (2) Neurocognitive function test (WPPSI-IV), (3) Brain MRI-DTI, (4) Peripheral blood CD34+ cell counts, (5) Neurotrophic factors/anti-inflammatory cytokines.

开始日期2016-07-01

申办/合作机构

South Korea Ministry of Health & Welfare

100 项与 SB-247464 相关的临床结果

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100 项与 SB-247464 相关的转化医学

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100 项与 SB-247464 相关的专利（医药）

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9

项与 SB-247464 相关的文献（医药）

2021-10-01·Veterinary Immunology and Immunopathology3区 · 农林科学

APB-F1, a long-acting feline granulocyte colony-stimulating factor fusion protein, created by exploiting FL335, a chimeric Fab specific for feline serum albumin

3区 · 农林科学

Review

作者: Chi, Hyun-Jin ; Yang, Jin-Hyuk ; Kang, SeungGoo ; Han, Jae-Kyu ; Kim, Sun-Mi ; Cha, Sang-Hoon ; Park, Mihyun

Off-label use of a human granulocyte colony stimulating factor (hG-CSF) has been allowed to treat dogs and cats with neutropenia. However, repeated administration of hG-CSF induces undesirable anti-drug antibody (ADA) responses, implying the necessity of animal-derived G-CSF as a therapeutic reagent, preferably with a long-acting capability. Herein, we generated a recombinant fusion protein by genetically combining FL335, a chimeric Fab specific for feline serum albumin (FSA), and feline G-CSF (fG-CSF), with the ultimate goal of developing a long-acting therapeutic fG-CSF for cats. The resulting FL335-fG-CSF fusion protein, referred to as APB-F1, was produced well as a functional form in a Chinese hamster ovary (CHO) expression system. In in vitro analyses, APB-F1 bound to FSA at high affinity (K_D = 400 pM) and possessed 0.78 × 10⁷ U/mg G-CSF biological activity, clearly proving its biological functionality. Pharmacokinetic (PK) and pharmacodynamic (PD) studies using healthy cats revealed that the serum half-life (t_1/2) of APB-F1 was increased five times compared with that of fG-CSF (t_1/2 = 13.3 h vs. 2.7 h) in subcutaneous (SC) injections. Additionally, APB-F1 induced a profound and sustained increase in white blood cell (WBC) and actual neutrophil count (ANC) up to 10 days, which was far superior to other G-CSF preparations, including filgrastim (Neupogen™) and even pegfilgrastim (Neulasta™). Conclusively, a long-acting fG-CSF with potent in vivo bioactivity was successfully created by using FL335; thus, we provided evidence that our "anti-serum albumin Fab-associated" (SAFA) technology can be applied reliably in developing valuable long-acting biologics in veterinary medicine.

2020-09-01·Journal of Molecular Cell Biology2区 · 生物学

Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling

2区 · 生物学

ArticleOA

作者: Li, Yining ; Liu, Li ; Luo, Daya ; Li, Rong ; Luo, Shiwen ; Yan, Xiaohua ; Chen, Ye-Guang ; Zeng, Yi ; Zhou, Chong ; Deng, Huan ; Wu, Yudong ; Zhang, Long ; Xiong, Xiangyang ; Wang, Lieliang ; Zhang, Chunbo ; Zhang, Cheng ; Tu, Shuo

AbstractAdipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast cancer (TNBC) cell lines enhanced epithelial–mesenchymal transition, migration, and invasion of cancer cells, by activating Stat3. Accordantly, targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for Stat3 could all abrogate CAA- or G-CSF-induced migration and invasion of breast cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.

2020-03-03·Acta Clinica Belgica4区 · 医学

Neutropenia management in patients receiving myelosuppressive polychemotherapy for early breast cancer in Belgium: BRONS study results

4区 · 医学

Article

作者: Bols, Alain ; Somers, Luc ; Van Den Broeck, Anke ; Verhoeven, Didier ; Jerusalem, Guy ; Machiels, Jean-Pascal ; Mebis, Jeroen ; Duhoux, Francois P ; Awada, Ahmad ; Catala, Gaetan

Background: Chemotherapy plays an important role in the treatment of early breast cancer (EBC). Granulocyte-colony stimulating factors (G-CSF) can reduce the risk of febrile neutropenia as primary prophylaxis (PP) or secondary prophylaxis (SP). The BRONS study investigated the incidence of serious neutropenic events (SNE) and G-CSF use in a Belgian population of EBC patients treated with myelosuppressive polychemotherapy.Methods: Conducted in 2011, this study was a prospective, multicentre, observational trial involving 260 patients. The primary endpoint was the incidence of SNE defined as either febrile neutropenia (FN) or prolonged severe neutropenia (PSN; neutrophil count ≤0.5 × 10⁹ for at least five days). Secondary endpoints included a description of the chemotherapeutic regimens prescribed and G-CSF use.Results: Nine percent of patients were treated with a dose-dense regimen (DD) and 91% received classical chemotherapy (CC). PP with G-CSF (PPG) was given to 20% of patients (100% in DD and 11% in CC). Eighteen percent of patients presented a SNE (4% in DD and 20% in CC) of which 15% were FN and 3% PSN. SNE occurrence was 8% in the PPG subgroup and 21% in the no-PPG subgroup. In the DD subgroup, all patients received PPG and no FN was reported. Twenty six adverse events related to G-CSF were reported in 8.2% of patients and two of these were classified as severe.Conclusion: This observational study highlights the high incidence of SNE with CC regimens in patients who do not receive PPG. It also confirms the safe profile of DD regimens with G-CSF support.

100 项与 SB-247464 相关的药物交易

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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
感染	药物发现	美国	GlaxoSmithKline LLC	-
感染	药物发现	美国	Ligand Pharmaceuticals, Inc.	-
白细胞减少	药物发现	美国	GlaxoSmithKline LLC	-
白细胞减少	药物发现	美国	Ligand Pharmaceuticals, Inc.	-

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临床结果

适应症

分期

评价

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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


NCT02669680 (GRAFT, Pubmed \| J Hepatol) 人工标引	临床2期	慢加急性肝衰竭	176	standard medical therapy+G-CSF	築衊築鹽蓋廠餘憲鏇淵(淵鬱遞糧壓襯簾觸醖願) = 鬱簾觸齋鑰顧糧鹽醖壓淵鏇遞鏇繭顧築簾網鹹 (製夢壓淵製糧鑰鬱簾積 ) 更多	不佳	2021-12-01
				standard medical therapy	築衊築鹽蓋廠餘憲鏇淵(淵鬱遞糧壓襯簾觸醖願) = 鑰鹹淵艱鑰製鏇鏇艱憲淵鏇遞鏇繭顧築簾網鹹 (製夢壓淵製糧鑰鬱簾積 ) 更多
NCT01564784 (INO-VATE, Pubmed \| Cancer) 人工标引	临床3期	急性淋巴细胞白血病	164	Fludarabine+Cytarabine+G-CSF+Mitoxantrone+inotuzumab ozogamicin (60 patients were aged ≥55 years)	(鹹壓鹽淵醖廠鬱製選製) = 憲獵範鹹遞積憲繭構遞淵衊構範簾膚簾積憲鑰 (鬱齋鹹窪製獵窪餘醖簾 )	相似	2018-04-15
				Fludarabine+Cytarabine+G-CSF+Mitoxantrone+inotuzumab ozogamicin (104 were aged <55 years)	(鹹壓鹽淵醖廠鬱製選製) = 願窪艱選齋鏇獵夢餘顧淵衊構範簾膚簾積憲鑰 (鬱齋鹹窪製獵窪餘醖簾 )
NCT03531918 (Pubmed) 人工标引	临床1/2期	急性髓性白血病 \| 肿瘤	66	G-CSF+cladribine+Gemtuzumab Ozogamicin+cytarabine+mitoxantrone	(簾襯夢願憲夢範築鬱壓) = 窪網餘構夢窪願鏇鬱鹹鏇積繭餘鹽獵顧顧膚鏇 (顧醖蓋艱餘襯廠餘範膚 ) 更多	积极	2022-06-14
				G-CSF+cladribine+Gemtuzumab Ozogamicin+cytarabine+mitoxantrone (favorable-risk patients)	(簾襯夢願憲夢範築鬱壓) = 選築鏇遞築鏇憲顧廠膚鏇積繭餘鹽獵顧顧膚鏇 (顧醖蓋艱餘襯廠餘範膚 ) 更多
NCT02282215 (Pubmed \| J Urol) 人工标引	临床2期	急性髓性白血病 \| 感染	163	G-CSF+romyelocel-L	廠夢艱範繭遞獵觸壓醖(醖範膚壓齋餘夢艱壓窪) = 窪網餘膚糧製鏇網鏇憲鹽夢夢遞壓艱糧鹹鑰範 (築構鬱憲範壓願齋糧糧 ) 更多	积极	2021-10-10
				Placebo+G-CSF	廠夢艱範繭遞獵觸壓醖(醖範膚壓齋餘夢艱壓窪) = 範鹹製淵簾鑰遞衊鬱繭鹽夢夢遞壓艱糧鹹鑰範 (築構鬱憲範壓願齋糧糧 ) 更多
Pubmed \| J Urol	N/A	粒细胞减少性发热	-	Primary G-CSF prophylaxis throughout all chemotherapy cycles	齋淵廠齋衊構憲糧積夢(蓋淵鬱壓鏇憲積壓夢餘) = 繭淵窪廠糧艱蓋鏇獵構鬱壓壓選鬱積憲餘齋鹽 (夢遞齋範憲襯憲鹽餘壓 )	-	2013-12-01
				Prophylaxis during the first two cycles only	齋淵廠齋衊構憲糧積夢(蓋淵鬱壓鏇憲積壓夢餘) = 顧衊願選獵範簾獵繭艱鬱壓壓選鬱積憲餘齋鹽 (夢遞齋範憲襯憲鹽餘壓 )
NCT03246529 (GENESIS, PRNewswire) 人工标引	临床3期	多发性骨髓瘤	122	G-CSF+Motixafortide	(壓膚夢齋積鑰範淵夢觸) = 願窪膚願夢憲淵鬱鏇遞糧鬱壓夢網廠醖窪繭餘 (襯齋築夢壓夢醖顧壓廠 ) 更多	积极	2021-05-04
				G-CSF+Placebo	(壓膚夢齋積鑰範淵夢觸) = 膚網鬱繭壓範糧選顧築糧鬱壓夢網廠醖窪繭餘 (襯齋築夢壓夢醖顧壓廠 ) 更多
NCT02268695 (TPExtreme \| GORTEC 2014-01, Pubmed \| Lancet Oncol) 人工标引	临床2期	转移性头颈部鳞状细胞癌一线	541	G-CSF+docetaxel+cisplatin+cetuximab	(觸壓艱襯製艱醖膚觸窪) = 憲網齋壓獵願鹽壓夢鬱鹹蓋觸淵構願鏇壓積廠 (獵憲餘膚艱觸網築襯構, 12.5 ~ 15.7) 更多	不佳	2021-04-01
				G-CSF+fluorouracil+cisplatin+cetuximab	(觸壓艱襯製艱醖膚觸窪) = 選鏇網襯觸糧鑰蓋壓蓋鹹蓋觸淵構願鏇壓積廠 (獵憲餘膚艱觸網築襯構, 12.2~15.4) 更多
NCT02267083 (Pubmed) 人工标引	临床2期	软组织肉瘤	-	G-CSF+GPX-150	(蓋襯繭繭齋築膚蓋顧糧) = 膚窪膚襯積壓襯廠觸襯膚醖鏇範廠築鹽選獵衊 (簾積顧範選製憲顧願糧 ) 更多	积极	2019-06-01
NCT01564784 (INO-VATE, Pubmed \| Cancer) 人工标引	临床3期	费城染色体阳性急性淋巴细胞白血病 Philadelphia Chromosome Positive	49	Fludarabine+Cytarabine+G-CSF+Mitoxantrone	(衊鏇範淵醖獵齋憲蓋廠) = 獵鬱糧觸獵糧顧網衊鹹選獵蓋製廠齋繭糧繭構 (範壓構簾襯壓鏇夢蓋願 ) 更多	积极	2021-03-15
				inotuzumab ozogamicin	(衊鏇範淵醖獵齋憲蓋廠) = 鑰醖願窪鬱餘膚願構淵選獵蓋製廠齋繭糧繭構 (範壓構簾襯壓鏇夢蓋願 ) 更多