NIKKOMYCIN Z

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25N5O10
Molecular Weight	495.44
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H]([C@H](N)C(=O)N[C@@H]([C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=CC(=O)NC2=O)C(O)=O)[C@H](O)C3=CC=C(O)C=N3

InChI

InChIKey=WWJFFVUVFNBJTN-VHDFTHOZSA-N

InChI=1S/C20H25N5O10/c1-7(13(28)9-3-2-8(26)6-22-9)11(21)17(31)24-12(19(32)33)16-14(29)15(30)18(35-16)25-5-4-10(27)23-20(25)34/h2-7,11-16,18,26,28-30H,21H2,1H3,(H,24,31)(H,32,33)(H,23,27,34)/t7-,11-,12-,13-,14-,15+,16+,18+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800007285 | https://www.ncbi.nlm.nih.gov/pubmed/8083179 | https://www.ncbi.nlm.nih.gov/pubmed/11870857 | https://www.ncbi.nlm.nih.gov/pubmed/19349517

Nikkomycin Z is an antifungal drug that inhibits chitin synthase. It has been reported that it inhibits chitin synthases (Chs) 1 and 3, but not 2, of Saccharomyces cerevisiae. Later it was found that nikkomycin Z inhibited all three Chs isozymes of Candida albicans (CaChs). The IC(50) value for CaChs1 is 15 uM, for CaChs2 0.8 uM, and for CaChs3 13 uM. Nikkomycin Z is under development as an orphan product for treatment of coccidioidomycosis. Nikkomycin Z has been used in trials studying the treatment and basic science of Coccidioidomycosis. In February 2006, nikkomycin z was designated as an orphan drug for the treatment of Coccidioidomycosis.

Originator

Approval Year

PubMed

Title	Date	PubMed
Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin synthase inhibitor (Nikkomycin Z) for inhibition and killing of fungal pathogens.	2000-09	10952614
Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.	2000-02	10639364
In vitro antifungal activity of nikkomycin Z in combination with fluconazole or itraconazole.	1999-06	10348760
Efficacy of nikkomycin Z in the treatment of murine histoplasmosis.	1998-09	9736565
Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo.	1992-06	1416829
Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and nikkomycin analogues as anticandidal prodrugs.	1991-01	1992114
Synergistic action of nikkomycins X and Z with papulacandin B on whole cells and regenerating protoplasts of Candida albicans.	1986-03	3521483

Patents

Sample Use Guides

In Vivo Use Guide

Safety and pharmacokinetics of nikkomycin Z were evaluated in healthy male subjects following single, rising oral doses ranging from 250 mg to 2,000 mg. Pharmacokinetics appeared linear over the range of 250 to 500 mg; however, relative bioavailability was about 62 to 70% for the 1,000-mg dose and 42 to 47% for doses between 1,500 and 2,000 mg.

Route of Administration: Oral

In Vitro Use Guide

Nikkomycin Z inhibited all three Chs isozymes of Candida albicans (CaChs). The IC(50) value for CaChs1 is 15 uM, for CaChs2 0.8 uM, and for CaChs3 13 uM.

Name

Type

Language

NSC-601906

Preferred Name

English

NIKKOMYCIN Z

Common Name

English

NEOPOLYOXIN C

Common Name

English

.BETA.-D-ALLOFURANURONIC ACID, 5-(((2S,3S,4S)-2-AMINO-4-HYDROXY-4-(5-HYDROXY-2-PYRIDINYL)-3-METHYL-1-OXOBUTYL)AMINO)-1,5-DIDEOXY-1-(3,4-DIHYDRO-2,4-DIOXO-1(2H)-PYRIMIDINYL)-

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

217505