LY-2886721 HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H16F2N4O2S.ClH
Molecular Weight	426.868
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]12COC[C@@]1(N=C(N)SC2)C3=C(F)C=CC(NC(=O)C4=NC=C(F)C=C4)=C3

InChI

InChIKey=JHHMCINLHBUFHB-GHDSXOKHSA-N

InChI=1S/C18H16F2N4O2S.ClH/c19-11-1-4-15(22-6-11)16(25)23-12-2-3-14(20)13(5-12)18-9-26-7-10(18)8-27-17(21)24-18;/h1-6,10H,7-9H2,(H2,21,24)(H,23,25);1H/t10-,18-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C18H16F2N4O2S
Molecular Weight	390.407
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25609634
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24530026

LY-2886721 is selective and potent BACE1 inhibitor developed by Eli Lilly. It reached phase II of clinical trials against Alzheimer'd disease, but its development was suspended due to possible liver toxicity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-secretase 1 21 Target ID: CHEMBL4822 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25609634	Inhibitor 8297	20.3 nM [IC50]
Beta secretase 2 3 Target ID: CHEMBL2525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25609634	Inhibitor 8297	10.2 nM [IC50]
Beta-secretase 1 21 Target ID: CHEMBL4822 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24704031	Inhibitor 8297	20.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT01561430	Primary		Phase II 1132	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT01807026	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Lessons from a BACE1 inhibitor trial: off-site but not off base.	2014 Oct	24530026
The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.	2015 Jan 21	25609634

Patents

Sample Use Guides

In Vivo Use Guide

15, 35 or 70 mg capsules orally once daily for 26 weeks

Route of Administration: Oral

In Vitro Use Guide

Human embryonic kidney cell line (HEK293) stably expressing APP751cDNA containing a Swedish mutation (HEK293Swe) was exposed to increasing concentrations of LY2886721(up to 1mkM) and the amount of amyloid_1–40 (A_1–40) and A_1–42 measured in the media as an index of BACE1 inhibition.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:14:34 GMT 2023` Edited by `admin` on `Sat Dec 16 05:14:34 GMT 2023`
Record UNII	HW8GJY7V7R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LY-2886721 HYDROCHLORIDE

Common Name

English

LY2886721 HYDROCHLORIDE

Code

English

2-PYRIDINECARBOXAMIDE, N-(3-((4AS,7AS)-2-AMINO-5,7-DIHYDRO-4H-FURO(3,4-D)(1,3)THIAZIN-7A(4AH)-YL)-4-FLUOROPHENYL)-5-FLUORO-, HYDROCHLORIDE (1:1)

Common Name

English

LY 2886721 HYDROCHLORIDE SALT

Code

English

N-(3-((4AS,7AS)-2-AMINO-5,7-DIHYDRO-4H-FURO(3,4-D)(1,3)THIAZIN-7A(4AH)-YL)-4-FLUOROPHENYL)-5-FLUORO-2-PYRIDINECARBOXAMIDE HYDROCHLORIDE

Common Name

English

Code System Code Type Description

FDA UNII

HW8GJY7V7R