Z-160

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C32H32N2O
Molecular Weight	460.6093
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(CC(C1=CC=CC=C1)C2=CC=CC=C2)N3CCN(CC3)C(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=VCPMZDWBEWTGNW-UHFFFAOYSA-N

InChI=1S/C32H32N2O/c35-31(25-30(26-13-5-1-6-14-26)27-15-7-2-8-16-27)33-21-23-34(24-22-33)32(28-17-9-3-10-18-28)29-19-11-4-12-20-29/h1-20,30,32H,21-25H2

HIDE SMILES / InChI

Description
Sources: http://www.businesswire.com/news/home/20131111005295/en/Zalicus-Reports-Results-Phase-2-Clinical-Trials | https://www.ncbi.nlm.nih.gov/pubmed/19815411

NMED-160 (also known as MK-6721, NP-118809, Z-160) is a potent N-type calcium channel blockers, which has good selectivity over L-type calcium channels. Neuromed Pharmaceuticals developed this compound for the treatment of the chronic pain. However, that study was discontinued in 2007 in spite of absence of adverse events, but because drug did not demonstrate the ideal, pharmaceutical characteristics considered necessary to advance the compound further in development. Then Zalicus, Inc. was developing that drug for the treatment of chronic neuropathic pain associated with lumbosacral radiculopathy and post-herpetic neuralgia and drug was in the phase II clinical trial. Nevertheless, based on the result from trials, where Z160 did not meet the primary endpoint, Zalicus was also discontinuing the Z160 program.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated N-type calcium channel alpha-1B subunit 12 Target ID: CHEMBL4478 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19815411	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Chronic pain 9 Sources: http://www.fiercebiotech.com/biotech/press-release-neuromed-pharmaceuticals-says-to-end-development-of-pain-drug	Primary	Phase II 1132	Unknown Approved Use Unknown
Lumbosacral radiculopathy 5 Sources: https://clinicaltrials.gov/ct2/show/NCT01655849	Primary	Phase II 1132	Unknown Approved Use Unknown
Postherpetic neuralgia 13 Sources: https://clinicaltrials.gov/ct2/show/NCT01757873	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
235 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
771 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1136 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
761 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
3.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19815411	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		Z-160 plasma	Rattus norvegicus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678253	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678253	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678253	yes [IC50 16.3601 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678253	yes [IC50 4.7724 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19815411/

PubMed

Title	Date	PubMed
Scaffold-based design and synthesis of potent N-type calcium channel blockers.	2009 Nov 15	19815411
Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors.	2010 Feb 15	20117000
Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides.	2013 Dec 17	23831344

Patents

Sample Use Guides

In Vivo Use Guide

375 mg BID (twice a day) for 6 weeks

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

Z-160

Common Name

English

Z160

Common Name

English

NP-118809

Common Name

English

1-(4-BENZHYDRYL-PIPERAZIN-1-YL)-3,3-DIPHENYLPROPAN-1-ONE

Systematic Name

English

MK-6721

Code

English

PIPERAZINE, 1-(DIPHENYLMETHYL)-4-(1-OXO-3,3-DIPHENYLPROPYL)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

387412