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Overview

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Nervous System Diseases

Other Diseases

Small molecule drug

Biological products

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Nervous System Diseases	1

Top 5 Drug Type	Count

Small molecule drug	3
Biological products	1

Top 5 Target	Count

PDE2A(Phosphodiesterase 2A)	2
MGAT(alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase)	1

This is a randomized, double-blind, placebo-controlled parallel group outpatient study that will utilize standard stroke rehabilitation outcome measures, as well as fMRI techniques in a subset of subjects, to evaluate the effect of HT-3951 on motor recovery and behavior in medically stable subjects following ischemic stroke.

Start Date01 Feb 2016

Sponsor / Collaborator

Dart NeuroScience LLC

100 Clinical Results associated with Dart NeuroScience LLC

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0 Patents (Medical) associated with Dart NeuroScience LLC

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19

Literatures (Medical) associated with Dart NeuroScience LLC

01 Jul 2020·Neurochemistry InternationalQ3 · MEDICINE

Rapid identification of a novel phosphodiesterase 7B tracer for receptor occupancy studies using LC─MS/MS

Q3 · MEDICINE

Article

Author: Renick, Joel ; Gu, Guibao ; Tabatabaei, Ali ; Breitenbucher, James Guy ; Heger, Lindsay ; Chen, Mi ; Keenan, Terence ; Santora, Vincent J ; Zook, Douglas ; Chung, DeMichael ; Vivian, Jeffrey ; Stauber, Kathe ; Chen, Jie ; Scott, Trevor

Phosphodiesterase 7B (PDE7B) inhibition has been considered as a therapeutic target for the treatment of several neurological disorders. Currently, there are no radio-labeled tracers available to determine receptor occupancy (RO) of this target. Developing such a tracer could greatly facilitate the identification of viable PDE7B inhibitors. In the current study, a liquid chromatography tandem mass spectrometry (LC─MS/MS) method was utilized to evaluate the brain distribution of unlabeled tracer candidates following intravenous micro-dosing. This novel approach resulted in an accelerated identification of a potential novel RO tracer for PDE7B. The identified molecule, Compound 30, showed reasonable target-tissue specificity (striatum/cerebellum ratio of 2.2) and suitable uptake (0.25% of the injected dose/g brain tissue) as demonstrated in rats dosed with the unlabeled compound. Compound 30 was subsequently labeled with tritium (³H). In vitro characterization of ³H-Compound 30 demonstrated that this compound possessed a high target affinity with a subnanomolar K_d (0.8 nM) and a B_max of 58 fmol/mg of protein using rat brain homogenate. Intravenous microdosing of ³H-Compound 30 showed preferential binding in the rat striatum, consistent with the mRNA distribution of PDE7B. In vitro displacement study with other structurally distinct PDE7B target-specific inhibitors using rat brain homogenate indicated that ³H-Compound 30 is an ideal tracer for K_i analysis. This is the first report of a preclinical tracer for PDE7B. With further characterization, Compound 30 may ultimately show the appropriate properties required to be further developed as a PDE7B PET ligand for clinical studies.

01 Apr 2019·Experimental Cell ResearchQ3 · MEDICINE

Heterochromatin Protein 1 (HP1) inhibits stem cell proliferation induced by ectopic activation of the Jak/STAT pathway in the Drosophila testis

Q3 · MEDICINE

Article

Author: Petrossian, Cynthia C ; Jones, D Leanne ; Boyle, Monica L ; Loza-Coll, Mariano A

Stem cells can divide asymmetrically with respect to cell fate, producing a copy of themselves (self-renewal), while giving rise to progeny that will differentiate along a specific lineage. Mechanisms that bias the balance towards self-renewal or extend the proliferative capacity of the differentiating progeny can result in tissue overgrowth and, eventually, the formation of tumors. Recent work has explored the role of heterochromatin and heterochromatin-associated proteins in the regulation of stem cell behavior under homeostatic conditions, but less is known about their possible roles in potentiating or suppressing stem cell overproliferation. Here we used ectopic activation of the Jak/STAT pathway in germline and somatic stem cells of the D. melanogaster testis as an in vivo model to probe the function of Heterochromatin Protein 1 (HP1) in stem cell overproliferation. Forced expression of HP1 in either early germ or somatic cells suppressed the overgrowth of testes in response to ectopic Jak/STAT activation. Interestingly, HP1 expression led to distinct phenotypes, depending on whether it was overexpressed in somatic or germ cells, possibly reflecting different cell-autonomous and non-autonomous effects in each cell type. Our results provide a new framework for further in vivo studies aimed at understanding the interactions between heterochromatin and uncontrolled stem cell proliferation, as well as the complex cross-regulatory interactions between the somatic and germline lineages in the Drosophila testis.

15 Jun 2018·The Journal of Organic ChemistryQ2 · CHEMISTRY

Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4-d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds

Q2 · CHEMISTRY

Article

Author: Valdez, Lino J. ; Bookser, Brett C. ; Moore, Curtis E. ; Weinhouse, Michael I. ; Dyck, Brian ; Rheingold, Arnold L. ; Stanczak, Pawel ; Na, Jim ; Burns, Aaron C. ; Valiere, Andrew N.

Alkylation of 4-methoxy-1 H-pyrazolo[3,4- d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-methyl product 4-methoxy-2-methyl-2 H-pyrazolo[3,4- d]pyrimidine (3b) in an 8/1 ratio over N1-methyl product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of ¹H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined the molecular weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO.

100 Deals associated with Dart NeuroScience LLC

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100 Translational Medicine associated with Dart NeuroScience LLC

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Discovery

1

2

Preclinical

Phase 1 Clinical

1

12

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

PDE2 inhibitor(Dart NeuroScience LLC) ( PDE2A )	-	Phase 1
DNS 006 ( MGAT )	-	Preclinical
DNS-003	Cognition Disorders More	Preclinical
DNS-8254 ( PDE2A )	Memory Disorders More	Discovery
HT-4313 ( GABA receptor x GABRA5 )	Cognition Disorders More	Discontinued