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

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

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
Synergistic action of nikkomycins X and Z with papulacandin B on whole cells and regenerating protoplasts of Candida albicans.	1986 Mar	3521483
Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and nikkomycin analogues as anticandidal prodrugs.	1991 Jan	1992114
Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo.	1992 Jun	1416829
Efficacy of nikkomycin Z in the treatment of murine histoplasmosis.	1998 Sep	9736565
Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.	2000 Feb	10639364

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

NIKKOMYCIN Z

Common Name

English

NSC-601906

Code

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