LY3000328 | CAS# 1373215-15-6 | Cathepsin S inhibitor

MedKoo Cat#: 407215 | Name: LY3000328

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

LY3000328 is a Cathepsin S inhibitor with excellent in vitro potency and selectivity against other cysteine proteases. LY3000328 is currently in clinical trials. Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA.

Chemical Structure

LY3000328

CAS#1373215-15-6

Theoretical Analysis

MedKoo Cat#: 407215

Name: LY3000328

CAS#: 1373215-15-6

Chemical Formula: C25H29FN4O5

Exact Mass: 484.2122

Molecular Weight: 484.53

Elemental Analysis: C, 61.97; H, 6.03; F, 3.92; N, 11.56; O, 16.51

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00	2 Weeks
10mg	USD 950.00	2 Weeks

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Synonym

LY3000328; LY-3000328; LY 3000328.

IUPAC/Chemical Name

(3R,4S)-4-(4-fluorobenzamido)-6-(4-(oxetan-3-yl)piperazin-1-yl)chroman-3-yl methylcarbamate

InChi Key

NDEBZCZEAVMSQF-GOTSBHOMSA-N

InChi Code

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

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

LY 3000328 (Z-FL-COCHO) is a potent and selective Cathepsin S (Cat S) inhibitor with IC50s of 7.7 and 1.67 nM for hCat S and mCat S.

In vitro activity:

U87 and U251 human glioblastoma cell lines were applied in this study. Cell migration and invasion ability were measured by wound healing assay and transwell assay. The CTSS inhibitor-Z-FL-COCHO (ZFL), could attenuate TGF-β-induced invasive growth as proven by wound healing and transwell assays. Reference: J Cancer. 2021 Jan 15;12(6):1592-1603. https://pubmed.ncbi.nlm.nih.gov/33613746/

In vivo activity:

The in vivo efficacies of 5 (LY 3000328) and 9 were studied in a mouse model of AAA (abdominal aortic aneurysm) (Figure 2). Both compounds exhibited a dose-responsive aortic diameter reduction at 1, 3, 10, and 30 mg/kg. However, 9 had a less profound effect than did 5. Reference: ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190634/

	Solvent	mg/mL	mM
Solubility
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.03

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 484.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wei L, Shao N, Peng Y, Zhou P. Inhibition of Cathepsin S Restores TGF-β-induced Epithelial-to-mesenchymal Transition and Tight Junction Turnover in Glioblastoma Cells. J Cancer. 2021 Jan 15;12(6):1592-1603. doi: 10.7150/jca.50631. PMID: 33613746; PMCID: PMC7890330. 2. Seo SU, Woo SM, Min KJ, Kwon TK. Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-induced apoptosis through upregulation of Bim expression. Biochem Biophys Res Commun. 2018 Apr 15;498(4):849-854. doi: 10.1016/j.bbrc.2018.03.068. Epub 2018 Mar 13. PMID: 29534961. 3. Zhao J, Yang Y, Wu Y. The Clinical Significance and Potential Role of Cathepsin S in IgA Nephropathy. Front Pediatr. 2021 Apr 12;9:631473. doi: 10.3389/fped.2021.631473. PMID: 33912521; PMCID: PMC8071879. 4. Jadhav PK, Schiffler MA, Gavardinas K, Kim EJ, Matthews DP, Staszak MA, Coffey DS, Shaw BW, Cassidy KC, Brier RA, Zhang Y, Christie RM, Matter WF, Qing K, Durbin JD, Wang Y, Deng GG. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42. doi: 10.1021/ml500283g. PMID: 25313327; PMCID: PMC4190634.

In vitro protocol:

In vivo protocol:

1. Zhao J, Yang Y, Wu Y. The Clinical Significance and Potential Role of Cathepsin S in IgA Nephropathy. Front Pediatr. 2021 Apr 12;9:631473. doi: 10.3389/fped.2021.631473. PMID: 33912521; PMCID: PMC8071879. 2. Jadhav PK, Schiffler MA, Gavardinas K, Kim EJ, Matthews DP, Staszak MA, Coffey DS, Shaw BW, Cassidy KC, Brier RA, Zhang Y, Christie RM, Matter WF, Qing K, Durbin JD, Wang Y, Deng GG. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42. doi: 10.1021/ml500283g. PMID: 25313327; PMCID: PMC4190634.

1: Jadhav PK, Schiffler MA, Gavardinas K, Kim EJ, Matthews DP, Staszak MA, Coffey DS, Shaw BW, Cassidy KC, Brier RA, Zhang Y, Christie RM, Matter WF, Qing K, Durbin JD, Wang Y, Deng GG. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42. doi: 10.1021/ml500283g. eCollection 2014 Oct 9. PubMed PMID: 25313327; PubMed Central PMCID: PMC4190634. 2: Payne CD, Deeg MA, Chan M, Tan LH, LaBell ES, Shen T, DeBrota DJ. Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects. Br J Clin Pharmacol. 2014 Dec;78(6):1334-42. doi: 10.1111/bcp.12470. PubMed PMID: 25039273; PubMed Central PMCID: PMC4256622.