CSF-1R antagonists(Colony stimulating factor 1 receptor antagonists), FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors), c-Kit inhibitors(Stem cell growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Philadelphia chromosome positive chronic myelogenous leukemia

Inactive Indication

Acute Myeloid LeukemiaChronic Myelomonocytic Leukemia

Originator Organization

Nerviano Medical Sciences S.r.l

Active Organization

Nerviano Medical Sciences S.r.l

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (EU)

Clinical Trials associated with NMS-03592088

EUCTR2021-005013-14-IT / Not yet recruitingPhase 1/2

A Phase I/II Combination Study of NMS-03592088 And Azacitidine for the Treatment of Patients With FLT3-Mutated AML with Relapsed /Refractory Disease or Who Are Unfit For Intensive Chemotherapy, or of CMML Patients. - Ph I/II Study of NMS-03592088+Aza in R/R or unfit FLT3-mut AML or CMML Pts

Start Date11 Jan 2022

Sponsor / Collaborator

Nerviano Medical Sciences Group SRL

NCT03922100 / TerminatedPhase 1/2

A Phase I/II Study of NMS-03592088, a FLT3, KIT and CSF1R Inhibitor, in Patients With Relapsed or Refractory AML or CMML

The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose and the recommended Phase II dose (RP2D), and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).

Start Date03 Apr 2019

Sponsor / Collaborator

Nerviano Medical Sciences S.r.l

100 Clinical Results associated with NMS-03592088

100 Translational Medicine associated with NMS-03592088

100 Patents (Medical) associated with NMS-03592088

Literatures (Medical) associated with NMS-03592088

09 Sep 2021·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies

Q1 · MEDICINE

Article

Author: Chen, Yadong ; Huang, Jianhang ; Liu, Xiaoyue ; Tang, Weifang ; Xu, Junyu ; Liu, Chenhe ; Zhang, Yanmin ; Dong, Ruinan ; Hou, Shaohua ; Zhang, Tianyi ; Li, Hongmei ; Lu, Tao ; Wang, Xinren

Hematologic malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biological studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematologic malignancies.

01 Jan 2021·European Journal of PharmacologyQ3 · MEDICINE

Pharmacology profile of F17464, a dopamine D3 receptor preferential antagonist

Q3 · MEDICINE

Article

Author: Gatti-McArthur, Silvia ; Sokoloff, Pierre ; Cavalleri, Laura ; Leriche, Ludovic ; Cosi, Cristina ; Martel, Jean-Claude ; Collo, Ginetta ; Auclair, Agnès L ; Moser, Paul C ; Heusler, Peter ; Gaudoux, Florence

F17464 (N-(3-{4-[4-(8-Oxo-8H-[1,3]-dioxolo-[4,5-g]-chromen-7-yl)-butyl]-piperazin-1-yl}-phenyl)-methanesulfonamide, hydrochloride) is a new potential antipsychotic with a unique profile. The compound exhibits high affinity for the human dopamine receptor subtype 3 (hD₃) (K_i = 0.17 nM) and the serotonin receptor subtype 1a (5-HT_1a) (K_i = 0.16 nM) and a >50 fold lower affinity for the human dopamine receptor subtype 2 short and long form (hD_2s/l) (K_i = 8.9 and 12.1 nM, respectively). [¹⁴C]F17464 dynamic studies show a slower dissociation rate from hD₃ receptor (t1/2 = 110 min) than from hD_2s receptor (t1/2 = 1.4 min) and functional studies demonstrate that F17464 is a D₃ receptor antagonist, 5-HT_1a receptor partial agonist. In human dopaminergic neurons F17464 blocks ketamine induced morphological changes, an effect D₃ receptor mediated. In vivo F17464 target engagement of both D₂ and 5-HT_1a receptors is demonstrated in displacement studies in the mouse brain. F17464 increases dopamine release in the rat prefrontal cortex and mouse lateral forebrain - dorsal striatum and seems to reduce the effect of MK801 on % c-fos mRNA medium expressing neurons in cortical and subcortical regions. F17464 also rescues valproate induced impairment in a rat social interaction model of autism. All the neurochemistry and behavioural effects of F17464 are observed in the dose range 0.32-2.5 mg/kg i.p. in both rats and mice. The in vitro - in vivo pharmacology profile of F17464 in preclinical models is discussed in support of a therapeutic use of the compound in schizophrenia and autism.

100 Deals associated with NMS-03592088

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 2	-	Nerviano Medical Sciences S.r.l	-
Acute Myeloid Leukemia	Preclinical	IT	Nerviano Medical Sciences S.r.l	03 Apr 2019
Acute Myeloid Leukemia	Preclinical	FR	Nerviano Medical Sciences S.r.l	03 Apr 2019
Acute Myeloid Leukemia	Preclinical	ES	Nerviano Medical Sciences S.r.l	03 Apr 2019
Chronic Myelomonocytic Leukemia	Preclinical	ES	Nerviano Medical Sciences S.r.l	03 Apr 2019
Chronic Myelomonocytic Leukemia	Discovery	FR	Nerviano Medical Sciences S.r.l	03 Apr 2019
Chronic Myelomonocytic Leukemia	Discovery	IT	Nerviano Medical Sciences S.r.l	03 Apr 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03922100 (AACR2023) Manual	Phase 1/2	FLT3 positive Acute Myeloid Leukemia FLT3 positive	44	NMS-03592088	(isgydzrgfb) = khspgpszjk gwlzgeozuz (zauiohqrrd ) View more	Positive	14 Apr 2023

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