NASTORAZEPIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H36N4O5
Molecular Weight	520.6199
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C(=O)CN1C2=CC=CC=C2N(C[C@@H](NC(=O)NC3=CC(=CC=C3)C(O)=O)C1=O)C4CCCCC4

InChI

InChIKey=VIJCCFFEBCOOIE-JOCHJYFZSA-N

InChI=1S/C29H36N4O5/c1-29(2,3)25(34)18-33-24-15-8-7-14-23(24)32(21-12-5-4-6-13-21)17-22(26(33)35)31-28(38)30-20-11-9-10-19(16-20)27(36)37/h7-11,14-16,21-22H,4-6,12-13,17-18H2,1-3H3,(H,36,37)(H2,30,31,38)/t22-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C29H36N4O5
Molecular Weight	520.6199
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20006921
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800016682 | http://www.zeria.co.jp/english/comp/co_0501.html |

Nastorazepide (Z-360) is a selective, orally available, gastrin/cholecystokinin 2 (CCK-2) receptor antagonist with potential antineoplastic activity. Z-360 binds to the gastrin/CCK-2 receptor, thereby preventing receptor activation by gastrin, a peptide hormone frequently associated with the proliferation of gastrointestinal and pancreatic tumor cells. It is currently under development as a therapeutic drug for pancreatic cancer, gastroesophageal reflux disease and peptic ulcers. The most commonly reported adverse events were nausea, abdominal pain, vomiting and fatigue.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cholecystokinin B receptor 9 Target ID: CHEMBL298 Sources: http://www.zeria.co.jp/english/comp/co_0501.html	Antagonist 2778		0.47 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97 Sources: http://www.zeria.co.jp/english/comp/co_0501.html http://adisinsight.springer.com/drugs/800016682 https://www.ncbi.nlm.nih.gov/pubmed/20006921	Primary	Phase II 1132	Unknown Approved Use Unknown
Metastatic pancreatic adenocarcinoma 5 Sources: https://clinicaltrials.gov/ct2/show/NCT02117258 https://www.ncbi.nlm.nih.gov/pubmed/17901954	Primary	Phase II 1132	Unknown Approved Use Unknown
Peptic ulcer 72 Sources: DOI: 10.1016/S0016-5085(08)81545-4 http://www.pharmacodia.com/web/drug/1_1566.html	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4434 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6756 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
18600 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
24030 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20006921/	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:		NASTORAZEPIDE CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587	inducer 389 inhibitor 1767	inducer 97 inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C19 1478 CYP2E1 882	P-gp 1537	CYP2A6 79 CYP2C19 293 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2A6 739	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2A6 739	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2C19 1553	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2C9 1819	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2D6 1891	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2E1 970	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP3A4 1925	inducer 1573 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	weak [IC50 10 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_236/_article/-char/ja/	yes [IC50 1 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363681355	no
CYP2D6 1217	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_239/_article/-char/ja/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00BFND	https://www.1pchem.com/search?query=1P00BFND
BLD Pharm	BD630531	http://www.bldpharm.com/search/Search.html?keyword=BD630531
Chem Scene	CS-5383	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5383
ChemShuttle	171845	https://www.chemshuttle.com/catalogsearch/result/?q=171845
MedChem Express	HY-17617	https://www.medchemexpress.com/search.html?q=HY-17617&ft=&fa=&fp=
MolPort	MolPort-046-417-193	https://www.molport.com/shop/molecule-link/MolPort-046-417-193
Molnova	M13278	https://www.molnova.com/en/serch-list.html?keywords=M13278
eMolecules	275077049	https://orderbb.emolecules.com/search/#?query=275077049
eMolecules	303152888	https://orderbb.emolecules.com/search/#?query=303152888
eMolecules	75542249	https://orderbb.emolecules.com/search/#?query=75542249
eMolecules	76738726	https://orderbb.emolecules.com/search/#?query=76738726
eNovation Chemicals	D548072	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D548072&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1006717196	https://mcule.com/MCULE-1006717196/

PubMed

Title	Date	PubMed
CCK-2/gastrin receptor signaling pathway is significant for gemcitabine-induced gene expression of VEGF in pancreatic carcinoma cells.	2011 Oct 24	21839751
Potential clinical indications for a CCK(2) receptor antagonist.	2016 Dec	27710813

Patents

Sample Use Guides

In Vivo Use Guide

60, 120 or 240 mg, twice daily (28-day cycle).

Route of Administration: Oral

In Vitro Use Guide

In PANC-1 cells, gemcitabineinduced expression of HIF-1alpha gene was suppressed by treatment with 0.1 μM Z-360.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:23:39 GMT 2023` Edited by `admin` on `Sat Dec 16 09:23:39 GMT 2023`
Record UNII	R22TMY97SG
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NASTORAZEPIDE

Official Name

English

Z-360 FREE ACID

Code

English

BENZOIC ACID, 3-(((((3R)-5-CYCLOHEXYL-1-(3,3-DIMETHYL-2-OXOBUTYL)-2,3,4,5-TETRAHYDRO-2-OXO-1H-1,5-BENZODIAZEPIN-3-YL)AMINO)CARBONYL)AMINO)-

Systematic Name

English

Nastorazepide [WHO-DD]

Common Name

English

R-(-)-Z-360 FREE ACID

Code

English

nastorazepide [INN]

Common Name

English

Code System Code Type Description

PUBCHEM

9872609