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
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
| Molecular Formula | C25H29FN4O5 |
| Molecular Weight | 484.52 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25039273
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
Cmax
| 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 |
T1/2
| 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 |
Sample Use Guides
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 12:13:48 GMT 2023
by
admin
on
Sat Dec 16 12:13:48 GMT 2023
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| Record UNII |
1210T8CX6K
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| Record Status |
Validated (UNII)
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LY-3000328
Created by
admin on Sat Dec 16 12:13:48 GMT 2023 , Edited by admin on Sat Dec 16 12:13:48 GMT 2023
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PRIMARY | MedKoo CAT NO.: 407215, CAS NO.: 1373215-15-6Description: 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. (last updated: 11/11/2015).Synonyms: LY3000328, LY-3000328, LY 3000328. | ||
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1210T8CX6K
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admin on Sat Dec 16 12:13:48 GMT 2023 , Edited by admin on Sat Dec 16 12:13:48 GMT 2023
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1373215-15-6
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DTXSID40737323
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67475270
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ACTIVE MOIETY |
Originator: Eli Lilly; Orphan Drug Status: No; On Fast track: No; Highest Development Phase: No development reported for Unspecified; Most Recent Events: 30 Apr 2014 No development reported - Phase-I for Undefined indication in USA (PO), 01 Feb 2012 Phase-I clinical trials in Undefined indication in USA (PO), 18 Jan 2012 Preclinical trials in Undefined indication in USA (PO)
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ACTIVE MOIETY |
AIM: The aim of this study was to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LY3000328 when administered as single escalating doses to healthy volunteers.
RESULTS: All doses of LY3000328 were well tolerated, with linear pharmacokinetics up to the 300mg dose. The pharmacodynamic activity of LY3000328 was measured ex vivo showing a biphasic response to LY3000328, where CatS activity declines, then returns to baseline, and then increases to a level above baseline. CatS mass was also assessed post-dose which increased in a dose-dependent manner, and continued to increase after LY3000328 had been cleared from the body. CatS specific activity was additionally calculated to normalize CatS activity for changes in CatS mass. This demonstrated the increase in CatS activity was attributable to the increase in CatS mass detected in plasma.
CONCLUSION: A specific inhibitor of CatS which is cleared quickly from plasma may produce a transient decrease in plasma CatS activity which is followed by a more prolonged increase in plasma CatS mass which may have implications for the future clinical development of inhibitors of CatS.
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