Delving into the Latest Updates on TD-6450 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Hepatitis C virus NS 5 protein

Mechanism

Hepatitis C virus NS 5 protein inhibitors

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis C

Inactive Indication

Chronic hepatitis C genotype 1bChronic hepatitis C genotype 3Mandibuloacral Dysplasia With Type a Lipodystrophy+ [1]

Originator Organization

Theravance Biopharma, Inc.

Active Organization

Theravance Biopharma, Inc.

Inactive Organization

Trek Therapeutics PBCStartup

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC46H54ClF3N8O7

InChIKeyQCJHQDPPKXRIOX-HGLYATPPSA-N

CAS Registry1433281-14-1

Author: Gamo, Francisco Javier ; Tarning, Joel ; Buffet, Pierre ; Ndour, Papa Alioune ; Roussel, Camille ; Dumas, Lucie ; Sissoko, Abdoulaye ; Duez, Julien ; Beher, Babette ; Amireault, Pascal ; Gamallo, Pablo ; McNamara, Case W ; Dussiot, Michael ; Hull, Mitchell V ; Fricot-Monsinjon, Aurélie ; Carucci, Mario ; Sanz, Laura Maria ; García-Barbazán, Irene ; Dao, Ming

Malaria parasites like Plasmodium falciparum multiply in red blood cells (RBC), which are cleared from the bloodstream by the spleen when their deformability is altered. Drug-induced stiffening of Plasmodium falciparum-infected RBC should therefore induce their elimination from the bloodstream. Here, based on this original mechanical approach, we identify safe drugs with strong potential to block the malaria transmission. By screening 13 555 compounds with spleen-mimetic microfilters, we identified 82 that target circulating transmissible form of P. falciparum. NITD609, an orally administered PfATPase inhibitor with known effects on P. falciparum, killed and stiffened transmission stages in vitro at nanomolar concentrations. Short exposures to TD-6450, an orally-administered NS5A hepatitis C virus inhibitor, stiffened transmission parasite stages and killed asexual stages in vitro at high nanomolar concentrations. A Phase 1 study in humans with a primary safety outcome and a secondary pharmacokinetics outcome ( https://clinicaltrials.gov , ID: NCT02022306) showed no severe adverse events either with single or multiple doses. Pharmacokinetic modelling showed that these concentrations can be reached in the plasma of subjects receiving short courses of TD-6450. This physiologically relevant screen identified multiple mechanisms of action, and safe drugs with strong potential as malaria transmission-blocking agents which could be rapidly tested in clinical trials.

100 Deals associated with TD-6450

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 2	-	Theravance Biopharma, Inc.	-
Chronic hepatitis C genotype 1b	Preclinical	US	Trek Therapeutics PBCStartup	01 May 2016
Chronic hepatitis C genotype 1b	Preclinical	NZ	Trek Therapeutics PBCStartup	01 May 2016
Chronic hepatitis C genotype 3	Preclinical	US	Theravance Biopharma, Inc.	01 May 2014
Mandibuloacral Dysplasia With Type a Lipodystrophy	Preclinical	US	Theravance Biopharma, Inc.	01 Feb 2014
Seasonal Affective Disorder	Preclinical	US	Theravance Biopharma, Inc.	01 Feb 2014