LY-3000328

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H29FN4O5
Molecular Weight	484.52
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)O[C@H]1COC2=C(C=C(C=C2)N3CCN(CC3)C4COC4)[C@@H]1NC(=O)C5=CC=C(F)C=C5

InChI

InChIKey=NDEBZCZEAVMSQF-GOTSBHOMSA-N

InChI=1S/C25H29FN4O5/c1-27-25(32)35-22-15-34-21-7-6-18(29-8-10-30(11-9-29)19-13-33-14-19)12-20(21)23(22)28-24(31)16-2-4-17(26)5-3-16/h2-7,12,19,22-23H,8-11,13-15H2,1H3,(H,27,32)(H,28,31)/t22-,23-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25313327
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25039273

LY-3000328 is a Cathepsin S inhibitor with excellent in vitro potency and selectivity against other cysteine proteases. LY-3000328 is currently in clinical trials. Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cathepsin S may provide a new treatment for AAA.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cathepsin S 1 Target ID: CHEMBL2954 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25313327	Inhibitor 8297		7.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Abdominal aortic aneurysm 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25039273 http://adisinsight.springer.com/drugs/800035584	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3870 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25039273	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LY-3000328 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
24900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25039273	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LY-3000328 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25039273	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LY-3000328 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009CI4	https://www.1pchem.com/search?query=1P009CI4
ApexBio Technology	A3284	https://www.apexbt.com/catalogsearch/result/?q=A3284
AstaTech	C72497	http://astatechinc.com/CPSResult.php?CRNO=C72497
BLD Pharm	BD630190	http://www.bldpharm.com/search/Search.html?keyword=BD630190
Chem Scene	CS-1120	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1120
ChemShuttle	157245	https://www.chemshuttle.com/catalogsearch/result/?q=157245
MedChem Express	HY-15533	https://www.medchemexpress.com/search.html?q=HY-15533&ft=&fa=&fp=
MolPort	MolPort-046-417-063	https://www.molport.com/shop/molecule-link/MolPort-046-417-063
Molnova	M11538	https://www.molnova.com/en/serch-list.html?keywords=M11538
MuseChem	I001435	https://www.musechem.com/product/I001435.html
ShangHai Biochempartner	BCP14297	http://www.biochempartner.com/search_BCP14297
Toronto Research Chemicals	L468955	https://www.trc-canada.com/product-detail/?CatNum=L468955
Toronto Research Chemicals	P992195	https://www.trc-canada.com/product-detail/?CatNum=P992195
eMolecules	44811268	https://orderbb.emolecules.com/search/#?query=44811268
eNovation Chemicals	D501789	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501789&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2904214349	https://mcule.com/MCULE-2904214349/
mcule	MCULE-9004172064	https://mcule.com/MCULE-9004172064/

PubMed

Title	Date	PubMed
Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects.	2014 Dec	25039273
Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm.	2014 Oct 9	25313327

Sample Use Guides

In Vivo Use Guide

Subjects were administered escalating LY-3000328 doses up to 300 mg (30, 100 and 300 mg) with food in a single dose study.

Route of Administration: Oral

In Vitro Use Guide

LY-3000328 showed low in vitro CYP450 inhibition (<15% at 10 uM for CYP3A4, CYP2D6, and CYP2C9

Name

Type

Language

LY-3000328

Common Name

English

LY 3000328

Code

English

N-((3R,4S)-3,4-DIHYDRO-3-(((METHYLAMINO)CARBONYL)OXY)-6-(4-(3-OXETANYL)-1-PIPERAZINYL)-2H-1-BENZOPYRAN-4-YL)-4-FLUOROBENZAMIDE

Systematic Name

English

BENZAMIDE, N-((3R,4S)-3,4-DIHYDRO-3-(((METHYLAMINO)CARBONYL)OXY)-6-(4-(3-OXETANYL)-1-PIPERAZINYL)-2H-1-BENZOPYRAN-4-YL)-4-FLUORO-

Systematic Name

English

Code System Code Type Description

MANUFACTURER PRODUCT INFORMATION

LY-3000328