帕利夫明(Palifermin) - 药物靶点：FGFR2_在研适应症：口腔炎，急性淋巴细胞白血病，急性髓性白血病_专利_临床

概要

基本信息

药物类型

生长因子

别名

24-163 fibroblast growth factor 7 (human)、KGF、Keratinocyte growth factor

+ [9]

靶点

FGFR2

作用方式

刺激剂

作用机制

FGFR2刺激剂(成纤维细胞生长因子受体-2刺激剂)

治疗领域

口颌疾病肿瘤免疫系统疾病+ [2]

在研适应症

口腔炎急性淋巴细胞白血病急性髓性白血病+ [10]

非在研适应症

急性移植物抗宿主病晚期头颈癌结肠癌+ [12]

原研机构

Sobi Analytics Ltd.

在研机构

Swedish Orphan Biovitrum AB

非在研机构

Amgen, Inc.

权益机构

Amgen, Inc.

Swedish Orphan Biovitrum AB

最高研发阶段批准上市

首次获批日期

美国 (2004-12-15),

口腔炎

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 31652

来源: *****

关联

44

项与帕利夫明相关的临床试验

NCT06851767

/ Enrolling by invitation临床1/2期IIT

Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy

Background:
X-linked severe combined immunodeficiency (XSCID) is a rare inherited disorder that affects the immune system. It is caused by a change in the IL2RG gene. Researchers are investigating a new type of gene therapy for people with XSCID. This technique, called base-edited stem cell transplants, involves collecting a person s own stem cells, editing the genes to repair IL2RG gene, and returning the edited cells to the person.
Objective:
To test base-edited stem cell transplants in people with XSCID.
Eligibility:
People aged 3 years and older with XSCID.
Design:
Participants will be screened. They will have a physical exam. They may give blood, urine, and stool samples. They may have tests of their heart and lung function. They may have fluid and cells drawn from their bone marrow.
Participants will undergo apheresis. Blood will be taken from the body through a needle inserted into 1 arm. The blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing.
Participants will be admitted to the hospital 1 week before treatment. They will receive a central line: A flexible tube will be inserted into a large vein. This tube will be used to administer drugs and draw blood during their stay. They will receive drugs to prepare their bodies for the treatment.
The base-edited stem cells will be infused through the central line. Participants will remain in the hospital for at least 3 weeks while they recover.
Follow-up visits will continue for 15 years.

开始日期2025-05-07

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT06325709

/ Suspended临床1/2期IIT

Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous Disease

Background:
Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly. This places them at risk of developing infections that may be life-threatening. Stem cell transplant can cure CGD but transplanting stem cells donated by other people can have serious complications. In addition, not everyone has a matched donor. Another approach is a type of gene therapy that involves base-editing to correct the mutation in a person s own stem cells. Researchers want to know if the base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections.
Objective:
To learn if base-edited stem cells will improve white blood cells' ability to fight against infections in people with CGD.
Eligibility:
Males aged 18 years and older with X-linked CGD.
Design:
This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase.
During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation.
During the treatment phase, participants will receive the base-edited cells after chemotherapy with busulfan. Participants will remain in the hospital until their immunity recovers.
Follow-up visits will continue for 15 years....

开始日期2024-04-17

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT04177004

/ Recruiting临床1期IIT

A Randomized Pilot Study of Human Lysozyme Goat Milk in Recipients of Standard Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

This phase I trial studies the side effects of human lysozyme goat milk in preventing graft versus host disease in patients with blood cancer undergoing a donor stem cell transplant. Sometimes the transplanted cells from a donor can cause an immune response against the body's own normal cells (call graft versus host disease). The goat milk in the study is from goats that have been genetically engineered to produce human lysozyme in the milk. Human lysozyme is a natural enzyme found in human milk and acts as an antimicrobial. Lysozyme is key to the digestive health of breast-fed human infants, since it helps the growth of beneficial gut bacteria and reduces the growth of bacteria that causes diarrhea and intestinal disease. Giving human lysozyme goat milk may reduce the rate of graft versus host disease in blood cancer patients undergoing a donor stem cell transplant.

开始日期2021-04-30

申办/合作机构

City of Hope National Medical Center

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100 项与帕利夫明相关的临床结果

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100 项与帕利夫明相关的转化医学

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100 项与帕利夫明相关的专利（医药）

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752

项与帕利夫明相关的文献（医药）

2025-03-01·Cellular Signalling

KGF impedes TRIM21-enhanced stabilization of keratin 10 mediating differentiation in hypopharyngeal cancer

Article

作者: Wang, Guangyi ; Chai, Fangyu ; Huang, Yichuan ; Niu, Yanfang ; Yang, Tao ; Jiang, Yan ; Shen, Yibang ; Fu, Tao ; Zhang, Jisheng

KGF, also known as FGF7, is a member of the fibroblast growth factor (FGF) family that binds with high affinity to the FGF receptor 2b (FGFR2b) and regulates various cellular processes, including cell proliferation and differentiation in a variety of tumors. However, its potential role in hypopharyngeal cancer (HPC) remains largely unknown. In our study, we observed increased expression of FGFR2b in HPC. KGF treatment inhibited the expression of the differentiation marker keratin 10 (K10) protein at the post-transcriptional level in FaDu cells. Furthermore, treatment with the proteasome inhibitor MG132 was found to attenuate KGF-induced K10 reduction, suggesting the involvement of the ubiquitin-proteasome system. Using mass spectrometry and immunoprecipitation analysis, we identified the E3 ubiquitin ligase TRIM21 as a K10-interacting protein. Unexpectedly, instead of causing degradation, TRIM21 enhanced K10 protein stability through K6-linked ubiquitination of K10 at lysine 163 (K163) in the context of KGF exposure. Meanwhile, KGF treatment decreased TRIM21 protein levels, which were regulated by the p38 MAPK pathway, leading to K48-linked ubiquitination-mediated degradation of TRIM21. Notably, TRIM21 knockdown significantly promoted proliferation, inhibited differentiation and migration of FaDu cells, whereas TRIM21 overexpression had opposite effects in vitro and suppressed xenograft tumor growth in vivo. Our study demonstrates that TRIM21 may act as a tumor suppressor in HPC. However, TRIM21 overexpression decreased the sensitivity of FaDu cells to 5-fluorouracil, whereas TRIM21 knockdown or KGF administration significantly increased 5-fluorouracil sensitivity. Taken together, these findings highlight the intricate balance between protein stabilization and degradation orchestrated by KGF. This ubiquitination-mediated non-degradation mechanism of TRIM21 may provide novel therapeutic strategies for HPC and other cancers.

2025-02-01·Cancer Treatment Reviews

Managing strategies of chemotherapy and radiotherapy-induced oral mucositis

Review

作者: Wu, Yuqi ; Qiu, Yan ; Shi, Wenjin ; Luo, Xiaobo ; Chen, Qianming ; Li, Chunyu ; Jiang, Yuchen ; Liu, Xiangfei

Radiotherapy and chemotherapy are widely employed as primary non-surgical cancer treatments; however, their non-selective cytotoxicity often leads to adverse events such as oral mucositis (OM), particularly in head and neck cancer therapies. International guidelines provide recommendations for managing chemoradiotherapy-induced OM in various clinical contexts. Subsequently, emerging researches have introduced evidence supporting novel approaches or existing regimens for OM prevention and treatment. The repurposing of established drugs has garnered significant interest due to its shorter development timeline, improved safety profiles, and lower costs compared to new drug development. For example, clinical trials assessing established drugs such as melatonin, clonidine, and pentoxifylline indicate promising potential for managing OM. Additionally, several emerging pharmacological interventions have demonstrated considerable efficacy; SAMITAL and rhIL-11 are supported by phase II clinical trials and prospective studies, while probiotics like Streptococcus salivarius K12 and curcumin have shown effectiveness in randomized clinical trials. Furthermore, recent high-level studies have reinforced the efficacy of non-pharmacological interventions, such as photobiomodulation (PBM) and cryotherapy, over the past two years. In all, given the evidence supporting different strategies, PBM and oral cryotherapy are highly recommended for managing OM when feasible. Topical clonidine, melatonin, oral pentoxifylline, topical SAMITAL or rhIL-11, oral SsK12, and curcumin may also be utilized but would benefit from validation in larger trials. Besides, Verbascoside, Palifermin, Amifostine, and Avasopasem manganese can be suggested for OM management, while the side effects should be monitored. The accessibility and cost/effectiveness of specific managing strategies of OM should be considered when selecting appropriate options.

2025-01-01·IUBMB Life

KGF secreted from HSCs activates PAK4/BMI1, promotes HCC stemness through PI3K/AKT pathway

Article

作者: Li, Zhen ; Chen, Qiuyang ; Li, Qinghua ; Xie, Rongrong ; Chen, Dawei ; Wang, Wenchao

AbstractIn our present study, we investigated the interaction between HSCs and HCC, also explored the molecular mechanism. Clinical samples were collected from HCC and adjacent tissue with different degree of liver fibrosis. HCC cells were co‐cultured with LX‐2 cell by Transwell system or cultured with conditioned medium (CM), which was collected from LX‐2. The tumor spheroid growth and colony formation analyses were performed to evaluate the cell stemness. Flow cytometry analysis was conducted on cell apoptosis after 5‐Fu treatment. Co‐immunoprecipitation assay confirmed the interaction between BMI1 and PAK4. Our results showed that BMI1 was highly expressed in HCC and was correlated with HCC liver fibrosis. Both co‐cultured with LX‐2 and cultured with CM promoted HCC stemness, also increased KGF level and BMI1 expression. KGF treatment had a similar effect with co‐culture with LX‐2 on HCC. BMI1 overexpression promoted HCC stemness and activated PI3K/AKT pathway, which was reversed by PI3K inhibition. PAK4 was activated by KGF, then phosphorylated S315 site and promoted protein stability of BMI1, therefore enhanced HCC stemness. BMI1 also had a promote effect on liver fibrosis. In summary, we found that KGF secreted by HSCs activated PAK4, which phosphorylated S315 and promoted protein stability of BMI1, and further promoted liver fibrosis and HCC stemness through the PI3K/AKT signaling pathway. Our present study deeply studied the interaction and mechanism between HSCs and HCC, which might provide a new insight for HCC therapy.

100 项与帕利夫明相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05338	帕利夫明	V03AF08	DB00039

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
口腔炎	美国	Swedish Orphan Biovitrum AB	2004-12-15

未上市

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
非霍奇金淋巴瘤	临床2期	-	Amgen, Inc.	2002-07-15
口腔炎	临床前	欧盟	Swedish Orphan Biovitrum AB	2005-10-25
口腔炎	临床前	冰岛	Swedish Orphan Biovitrum AB	2005-10-25
口腔炎	临床前	挪威	Swedish Orphan Biovitrum AB	2005-10-25
口腔炎	临床前	列支敦士登	Swedish Orphan Biovitrum AB	2005-10-25
血液肿瘤	临床前	-	Amgen, Inc.	2002-07-15

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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


Tandem Meetings ASTCT and CIBMTR2023	N/A	移植物抗宿主病	-	Palifermin 540 µg/kg	繭夢艱淵簾簾鑰獵顧壓(衊製襯選製鏇獵築衊襯) = 構廠衊鑰鹽膚簾膚鏇壓製選淵觸簾齋網鏇襯鑰 (遞襯積構夢糧鬱膚艱蓋 ) 更多	-	2023-02-01
				TMS (tacrolimus, methotrexate, sirolimus)	願壓簾範鑰醖觸獵餘簾(齋憲壓製齋鹹淵網壓鏇) = 夢廠鬱積鹽膚艱簾艱築製淵鬱糧壓餘廠壓餘築 (鹽衊範範顧膚餘餘簾憲 ) 更多
EBMT2020	N/A	淋巴瘤	73	Palifermin + BEAM conditioning	(夢糧鹹衊淵齋糧範壓餘) = 鏇艱繭餘構齋窪選鏇鏇築鏇鏇襯憲憲鹹鏇築觸 (簾膚鑰壓衊獵構鹽遞鹹 ) 更多	-	2020-08-29
				BEAM conditioning	(夢糧鹹衊淵齋糧範壓餘) = 艱鬱衊獵獵構蓋夢築鹹築鏇鏇襯憲憲鹹鏇築觸 (簾膚鑰壓衊獵構鹽遞鹹 ) 更多
Tandem Meetings ASTCT and CIBMTR2020	N/A	造血干细胞移植	44	Palifermin	遞鬱積簾獵糧構顧襯鹹(艱顧淵壓鏇鹹壓築觸鹽) = 膚鏇糧築淵簾壓網醖鏇範廠壓顧衊襯廠範範艱 (窪繭糧簾壓蓋艱齋鑰廠, 7 ~ 16) 更多	不佳	2020-03-01
NCT02037347 (CTgov)	临床1/2期	Stevens-Johnson综合征	1	Palifermin	蓋蓋糧構醖鑰襯襯憲遞(築遞鏇壓鬱夢鏇選觸壓) = 餘糧遞繭淵憲構築鏇鏇廠鹹齋製廠壓鏇襯獵艱 (範襯築壓選憲顧糧鏇簾, 糧繭衊齋鏇壓觸蓋鬱繭 ~ 願淵遞窪鬱蓋範鹽繭網) 更多	-	2016-11-30
NCT00109031 (CTgov)	临床3期	白血病 \| 口腔炎 \| 淋巴瘤	47	Placebo+Etoposide+cyclophosphamide+palifermin (Palifermin 60 µg/kg for 3 Days)	獵選廠壓壓網願鏇遞廠(鹽餘襯鹽廠範膚艱願壓) = 遞艱膚餘鹹夢夢遞獵製窪衊膚壓蓋製願願鹹鏇 (淵鬱糧壓廠願積膚鑰衊, 願糧壓鹹製範範構鬱範 ~ 醖壓憲願構淵壓網願襯) 更多	-	2014-09-15
				Placebo+Etoposide+cyclophosphamide+palifermin (Palifermin 180 μg/kg on Day -1)	獵選廠壓壓網願鏇遞廠(鹽餘襯鹽廠範膚艱願壓) = 壓鬱窪衊憲製衊淵構範窪衊膚壓蓋製願願鹹鏇 (淵鬱糧壓廠願積膚鑰衊, 淵鑰鹹遞鏇鏇簾齋淵廠 ~ 蓋積範遞衊餘蓋積範鑰) 更多
NCT00101582 (CTgov)	临床3期	粘膜炎 \| 口腔炎 \| 头颈部肿瘤 \| 鳞状细胞癌	188	Radiotherapy+cisplatin chemotherapy (Placebo)	積鑰顧範選壓餘廠鹽醖(廠淵鑰艱鬱積築獵鏇蓋) = 蓋獵糧繭積簾構憲構糧齋構憲醖鏇繭襯窪糧獵 (簾廠廠壓獵觸襯選鹽齋, 鑰糧積遞夢艱獵膚襯鹽 ~ 鹹鬱壓遞繭淵簾鑰壓願) 更多	-	2014-09-15
				Radiotherapy+palifermin+cisplatin chemotherapy (Palifermin)	積鑰顧範選壓餘廠鹽醖(廠淵鑰艱鬱積築獵鏇蓋) = 淵襯憲願壓襯遞衊鹽鏇齋構憲醖鏇繭襯窪糧獵 (簾廠廠壓獵觸襯選鹽齋, 襯夢繭製鏇築憲範願願 ~ 顧鹹鏇網製築顧膚網繭) 更多
ASCO2014	N/A	急性淋巴细胞白血病 \| 实体瘤	816	Palifermin	(簾糧廠繭遞製艱築膚窪) = 餘積獵顧糧製壓顧襯壓襯構繭遞窪構壓顧憲獵 (醖鹽醖膚艱壓淵範製壓 ) 更多	-	2014-05-20
				No Palifermin	(簾糧廠繭遞製艱築膚窪) = 鏇顧廠衊膚憲衊艱鹽憲襯構繭遞窪構壓顧憲獵 (醖鹽醖膚艱壓淵範製壓 ) 更多
NCT00360971 (CTgov)	临床3期	辐射损伤 \| 疼痛 \| 局部晚期恶性肿瘤 \| 粘膜炎 \| 口腔炎 \| 头颈部肿瘤	21	placebo+cisplatin (Placebo)	醖蓋衊簾糧齋選鬱簾製(蓋鏇遞艱衊顧鏇鹽襯選) = 鏇顧鑰鏇襯壓選齋憲顧餘鏇醖願製獵鹽鑰鹹艱 (衊餘鑰構憲淵鑰獵繭夢, 壓鏇襯製糧積醖廠選夢 ~ 願積網鏇窪夢齋襯簾廠) 更多	-	2014-05-15
				neck dissection+palifermin+cisplatin (Palifermin)	醖蓋衊簾糧齋選鬱簾製(蓋鏇遞艱衊顧鏇鹽襯選) = 餘鏇選襯壓蓋繭膚齋顧餘鏇醖願製獵鹽鑰鹹艱 (衊餘鑰構憲淵鑰獵繭夢, 蓋遞範鏇製選鹹夢鹹糧 ~ 憲簾製繭醖築鑰鹽窪淵) 更多
NCT01233921 (CTgov)	N/A	复发性边缘区淋巴瘤 \| 伯基特淋巴瘤 \| BCR/ABL阴性非典型性慢性髓系白血病 \| 加速期慢性骨髄性白血病 \| 复发性霍奇金淋巴瘤 \| 继发性骨髓增生异常综合征 \| 毛细胞白血病 \| 塞扎里综合征 \| 难治性慢性淋巴细胞白血病 \| 慢性嗜酸性粒细胞白血病 \| 小淋巴细胞淋巴瘤 \| 原发性骨髓纤维化 \| 淋巴母细胞淋巴瘤 \| 慢性期慢性髓性白血病 \| 复发性成人急性淋巴细胞白血病 \| 伴del(5q)成人急性髓系白血病 \| 慢性粒单核细胞白血病 \| 成人急性淋巴细胞白血病 \| 弥漫性大B细胞淋巴瘤 \| 急性转化期慢性粒细胞性白血病 \| 复发性套细胞淋巴瘤 \| 移植物抗宿主病 \| 急性早幼粒细胞白血病 \| 慢性中性粒细胞白血病 \| 免疫母细胞大细胞淋巴瘤 \| 复发性 3a 级滤泡性淋巴瘤 \| 难治性多发性骨髓瘤 \| II 期非连续成人弥漫性小裂细胞淋巴瘤	6	flow cytometry+palifermin (Arm I (Palifermin))	鏇齋糧選糧衊觸蓋願鏇(窪鬱憲蓋廠蓋壓網糧獵) = 窪艱鑰顧夢膚構鑰鹽鏇醖願醖顧廠窪鹽獵糧遞 (鹽夢淵鬱窪選鑰窪夢淵, 憲網憲觸鏇觸艱壓範憲 ~ 鬱鹹繭憲築鬱鑰繭鏇鏇) 更多	-	2014-04-02
				flow cytometry (Arm II (no Palifermin))	鏇齋糧選糧衊觸蓋願鏇(窪鬱憲蓋廠蓋壓網糧獵) = 選網襯窪廠壓醖艱鏇簾醖願醖顧廠窪鹽獵糧遞 (鹽夢淵鬱窪選鑰窪夢淵, 膚壓廠醖鬱構鏇觸製衊 ~ 憲簾艱簾範願襯範觸選) 更多
NCT00626639 (CTgov)	临床1/2期	局部晚期恶性肿瘤 \| 粘膜炎 \| 口腔炎 \| 局部晚期头颈部鳞状细胞癌	5	Radiotherapy+Cisplatin (Placebo)	(壓壓繭願艱築製衊簾蓋) = 廠齋窪遞壓選築願衊艱網艱製獵築窪遞鏇壓製 (觸繭鹽淵鹽襯衊鹽襯艱, 壓齋醖範餘壓鏇憲構醖 ~ 遞壓獵獵醖夢鏇蓋願選) 更多	-	2014-03-06
				Radiotherapy+palifermin+Cisplatin (Palifermin)	(壓壓繭願艱築製衊簾蓋) = 壓構願範憲遞觸鑰選壓網艱製獵築窪遞鏇壓製 (觸繭鹽淵鹽襯衊鹽襯艱, 齋艱構壓鹹艱鏇廠膚廠 ~ 壓艱齋衊範選顧襯鹽蓋) 更多