Delving into the Latest Updates on FF-10501 with Synapse

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.

Start Date01 Oct 2019

Sponsor / Collaborator

FUJIFILM Pharmaceuticals USA, Inc.

NCT02193958 / CompletedPhase 1/2

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.

Start Date01 Jul 2014

Sponsor / Collaborator

FUJIFILM Pharmaceuticals USA, Inc.

JPRN-jRCT2080222047 / Unknown statusPhase 1

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

Start Date19 Mar 2013

Sponsor / Collaborator

Toyama Chemical Co., Ltd.

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100 Clinical Results associated with FF-10501

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100 Translational Medicine associated with FF-10501

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100 Patents (Medical) associated with FF-10501

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Literatures (Medical) associated with FF-10501

02 Jul 2020·Leukemia & LymphomaQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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).

01 Nov 2019·International Journal of HematologyQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Feb 2018·Leukemia & LymphomaQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: Saito, Motoki ; Kyoden, Rie ; Oritani, Kenji ; Nozaki, Yusuke ; Ichii, Michiko ; Kito, Nobuko ; 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 Deals associated with FF-10501

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Myelomonocytic Leukemia	Phase 2	US	FUJIFILM Pharmaceuticals USA, Inc.	01 Jul 2014
Myeloproliferative Disorders	Phase 2	US	FUJIFILM Pharmaceuticals USA, Inc.	01 Jul 2014
Acute Myeloid Leukemia	Phase 2	-	Strategia Therapeutics, Inc.	-
Acute Myeloid Leukemia	Phase 2	-	FUJIFILM Holdings Corp.	-
Myelodysplastic Syndromes	Phase 2	-	Strategia Therapeutics, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02193958 (Pubmed) Manual	Phase 1/2	Acute Myeloid Leukemia \| Myelodysplastic Syndromes	38	FF-10501-01 (relapsed/refractory AML (n = 28) or myelodysplastic syndromes (MDS/CMML, n = 10))	(eretagmdck) = Most Phase 1 adverse events were disease-related and low-grade. nbbbezmjpi (ukuusqfqqa )	Negative	01 Aug 2020