FF-10501(FF-10501) - 药物靶点：IMPDH_在研适应症：急性髓性白血病，骨髓增生异常综合征_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

IMPDH

作用方式

抑制剂

作用机制

IMPDH抑制剂(肌苷-5 '-磷酸脱氢酶（IMPDH）家族抑制剂)

治疗领域

肿瘤血液及淋巴系统疾病

在研适应症

急性髓性白血病骨髓增生异常综合征

非在研适应症

慢性粒单核细胞白血病骨髓增生性疾病难治性血液恶性肿瘤

原研机构

FUJIFILM Holdings Corp.

在研机构

Strategia Therapeutics, Inc.

FUJIFILM Holdings Corp.

非在研机构

FUJIFILM Pharmaceuticals USA, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 FF-10501 相关的临床试验

NCT03486353

/ Withdrawn临床2期

A Phase 2 Study of FF-10501-01 in Combination with Azacitidine in Patients with Myelodysplastic Syndrome

The primary objective of the study is to determine the response rate according to the International Working Group Response criteria for the combination of FF-10501-01 and azacitidine in patients previously untreated with hypomethylating agents, with Int2/High risk MDS according to the IPSS, and Intermediate/High/Very-High risk MDS according to the IPSS-R, or who are otherwise candidates for treatment with azacitidine.

开始日期2019-10-01

申办/合作机构

FUJIFILM Pharmaceuticals USA, Inc.

NCT02193958

/ Completed临床1/2期

A Phase 1/2a, Dose Escalation Study of FF-10501-01 for the Treatment of Advanced Hematologic Malignancies

A Phase 1/2a Dose Escalation Study of FF-10501-01 in Patients with Relapsed or Refractory Hematological Malignancies to determine the safety and tolerability. A total of 6 cohorts will be enrolled in Phase 1 to establish the MTD. A total of 20 subjects with MDS/CMML treated at the RP2D are planned, including MDS/CMML subjects treated at the RP2D in Phase 1.

开始日期2014-07-01

申办/合作机构

FUJIFILM Pharmaceuticals USA, Inc.

JPRN-jRCT2080222047

/ Unknown status临床1期

Phase I study of FF-10501-01 in patients with Myelodysplastic Syndrome and continuous administration study

开始日期2013-03-19

申办/合作机构

Toyama Chemical Co., Ltd.

[+1]

100 项与 FF-10501 相关的临床结果

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100 项与 FF-10501 相关的转化医学

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100 项与 FF-10501 相关的专利（医药）

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4

项与 FF-10501 相关的文献（医药）

2020-07-02·Leukemia & Lymphoma4区 · 医学

Results of a Phase 1/2a dose–escalation study of FF-10501-01, an IMPDH inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndromes

4区 · 医学

Article

作者: Garcia-Manero, Guillermo ; Gerds, Aaron ; Bavisotto, Linda ; Carraway, Hetty E. ; Kurman, Michael ; Jabbour, Elias ; De Lumpa, Ricardo ; Pemmaraju, Naveen ; Maier, Gary ; Naqvi, Kiran ; Iwamura, Hiroyuki ; Mukherjee, Sudipto ; Ravandi, Farhad ; Sekeres, Mikkael A. ; Johansen, Mary ; Nazha, Aziz ; Murase, Motohiko ; Advani, Anjali ; Alvarado, Yesid ; Kantarjian, Hagop

FF-10501-01 potently inhibits inosine-5-monophosphate dehydrogenase (IMPDH), inducing anti-proliferative and pro-apoptotic effects in acute myeloid leukemia (AML) human cell lines resistant to hypomethylating agents. In this Phase 1/2a study, Phase 1 enrolled 38 patients with relapsed/refractory AML (n = 28) or myelodysplastic syndromes (MDS/CMML, n = 10) to receive FF-10501 oral doses 50-500 mg/m² BID for 14 or 21 days out of each 28-day cycle. Fifteen additional patients with HMA-resistant MDS/CMML (Phase 2a) were treated at 400 mg/m² BID for 21 days. Most Phase 1 adverse events were disease-related and low-grade. 3 of 19 (16%) evaluable AML patients achieved partial remission (31, 7, and 5 months). 2 of 20 (10%) evaluable MDS/CMML patients (Phase 1 and 2a) attained marrow complete remission, one continuing treatment for 17 months. While FF-10501-01 demonstrated clinical activity and target inhibition in heavily pretreated patients with AML and MDS/CMML, increased mucositis events led to Phase 2a closure (ClinTrials.gov#NCT02193958).

2019-11-01·International Journal of Hematology4区 · 医学

FF-10501 induces caspase-8-mediated apoptotic and endoplasmic reticulum stress-mediated necrotic cell death in hematological malignant cells

4区 · 医学

Article

作者: Takamatsu, Yasushi ; Matsumoto, Taichi ; Jimi, Shiro ; Hara, Shuuji ; Terada, Kazuki ; Suzumiya, Junji ; Mori, Masayoshi ; Migita, Keisuke

FF-10501 is a novel inhibitor of inosine monophosphate dehydrogenase (IMPDH). Clinical trials of FF-10501 for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are currently being conducted in the United States. Although it has been shown that FF-10501 induces apoptosis in hematological malignant cells, the intracellular mechanisms of this effect have not been characterized. We conducted an in vitro study to elucidate the mechanisms of FF-10501-induced cell death using 12 hematological malignant cell lines derived from myeloid and lymphoid malignancies. FF-10501 suppressed the growth of each cell line in a dose-dependent manner. However, the clinically relevant dose (40 μM) of FF-10501 induced cell death in three cell lines (MOLM-13, OCI-AML3, and MOLT-3). Investigation of the cell death mechanism suggested that FF-10501 induces both apoptotic and necrotic cell death. FF-10501-induced apoptosis was mediated by caspase-8 activation followed by activation of the mitochondrial pathway in MOLM-13 and MOLT-3 cells. FF-10501 induced necrotic cell death via endoplasmic reticulum stress in OCI-AML3 cells. The present study is the first to identify intracellular pathways involved in FF-10501-induced cell death.

2018-02-01·Leukemia & Lymphoma4区 · 医学

Molecular targeting of inosine-5’-monophosphate dehydrogenase by FF-10501 promotes erythropoiesis via ROS/MAPK pathway

4区 · 医学

Article

作者: Saito, Motoki ; Kyoden, Rie ; Oritani, Kenji ; Nozaki, Yusuke ; Kito, Nobuko ; Ichii, Michiko ; Yamazaki, Mao ; Komatsu, Kensuke ; Kanakura, Yuzuru ; Iwamura, Hiroyuki ; Murase, Motohiko

One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5'-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner. Interestingly, we found that metabolic conversion of IMP to hypoxanthine leads to elevation of reactive oxygen species (ROS). The differentiative effects of FF-10501 were abolished by the ROS scavenger dimethylthiourea or the p38 MAPK inhibitor SB203580. Furthermore, FF-10501 promoted erythropoiesis from CD34⁺ hematopoietic stem/progenitor cells, accompanied with ROS accumulation, while high-dose FF-10501 mainly showed cytotoxic effects. These findings denote the potential of IMPDH inhibition therapy with FF-10501 in amelioration of anemia in MDS patients.

100 项与 FF-10501 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
慢性粒单核细胞白血病	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2014-07-01
骨髓增生性疾病	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2014-07-01
难治性血液恶性肿瘤	临床2期	美国	FUJIFILM Pharmaceuticals USA, Inc.	2014-07-01
急性髓性白血病	临床2期	-	Strategia Therapeutics, Inc.	-
急性髓性白血病	临床2期	-	FUJIFILM Holdings Corp.	-
骨髓增生异常综合征	临床2期	-	Strategia Therapeutics, Inc.	-

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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


NCT02193958 (Pubmed) 人工标引	临床1/2期	急性髓性白血病 \| 骨髓增生异常综合征	38	FF-10501-01 (relapsed/refractory AML (n = 28) or myelodysplastic syndromes (MDS/CMML, n = 10))	(醖範餘衊夢餘遞鏇遞膚) = Most Phase 1 adverse events were disease-related and low-grade. 願構齋選簾簾廠獵獵鏇 (獵餘襯構窪繭鹹製簾簾 )	不佳	2020-08-01