LY2886721 | CAS#262036-49-6 | CAS#1262036-50-9 | BACE1 inhibitor

MedKoo Cat#: 522472 | Name: LY2886721

Description:

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

LY2886721 is a potent and selective BACE1 inhibitor. LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD).

Chemical Structure

LY2886721

CAS#1262036-50-9 (free base)

Theoretical Analysis

MedKoo Cat#: 522472

Name: LY2886721

CAS#: 1262036-50-9 (free base)

Chemical Formula: C18H16F2N4O2S

Exact Mass: 390.0962

Molecular Weight: 390.41

Elemental Analysis: C, 55.38; H, 4.13; F, 9.73; N, 14.35; O, 8.20; S, 8.21

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,150.00	Ready to ship

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Related CAS #

1262036-50-9 (free base) 1262036-49-6 (HCl )

Synonym

LY2886721; LY-2886721; LY 2886721.

IUPAC/Chemical Name

N-(3-((4aS,7aS)-2-amino-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

InChi Key

NIDRNVHMMDAAIK-YPMLDQLKSA-N

InChi Code

InChI=1S/C18H16F2N4O2S/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)/t10-,18-/m0/s1

SMILES Code

O=C(NC1=CC=C(F)C([C@@]23N=C(N)SC[C@]2([H])COC3)=C1)C4=NC=C(F)C=C4

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

Certificate of Analysis

View CoA: current batch, Lot#CRB60719

QC Data

View QC data: current batch, Lot#CRB60719

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LY2886721 is a beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC50 of 20.3 nM.

In vitro activity:

The in vitro cellular activity of LY2886721 was assessed (Table 2). The HEK293Swe model consisted of a human embryonic kidney cell stably expressing a cDNA encoding human APP harboring a Swedish mutation. Overnight exposure of HEK293Swe cells to increasing concentrations of LY2886721 showed a concentration-dependent decrease in the amount of Aβ secreted into the condition medium. Consistent with a mechanism of BACE inhibition, the EC50s for inhibition of Aβ1–40 and Aβ1–42 were essentially identical, 18.5 and 19.7 nm, respectively. These results were achieved in the absence of any overt cytotoxicity. Reference: J Neurosci. 2015 Jan 21;35(3):1199-210. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605527/

In vivo activity:

LY2886721 treatment improved glucose homeostasis and hepatic gluconeogenesis in diabetic PLB4 mice, as determined by improvements in basal glucose and glucose/pyruvate tolerance tests. Furthermore, LY2886721 improved hepatic insulin sensitivity, as indicated by enhanced basal hyperphosphorylation of insulin receptors. In PLB4 brains, altered basal conditions of APP expression and processing were detected, with beneficial effects on APP processing achieved by LY2886721 treatment. Reference: Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166149. https://www.sciencedirect.com/science/article/abs/pii/S092544392100082X?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	DMSO	26.7	68.31

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 390.41 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. May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN, Borders AR, Brier RA, Calligaro DO, Day TA, Ereshefsky L, Erickson JA, Gevorkyan H, Gonzales CR, James DE, Jhee SS, Komjathy SF, Li L, Lindstrom TD, Mathes BM, Martényi F, Sheehan SM, Stout SL, Timm DE, Vaught GM, Watson BM, Winneroski LL, Yang Z, Mergott DJ. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210. doi: 10.1523/JNEUROSCI.4129-14.2015. PMID: 25609634; PMCID: PMC6605527. 2. Dekeryte R, Franklin Z, Hull C, Croce L, Kamli-Salino S, Helk O, Hoffmann PA, Yang Z, Riedel G, Delibegovic M, Platt B. The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice. Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166149. doi: 10.1016/j.bbadis.2021.166149. Epub 2021 Apr 20. PMID: 33892080.

In vitro protocol:

In vivo protocol:

1. Dekeryte R, Franklin Z, Hull C, Croce L, Kamli-Salino S, Helk O, Hoffmann PA, Yang Z, Riedel G, Delibegovic M, Platt B. The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice. Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166149. doi: 10.1016/j.bbadis.2021.166149. Epub 2021 Apr 20. PMID: 33892080. 2. May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN, Borders AR, Brier RA, Calligaro DO, Day TA, Ereshefsky L, Erickson JA, Gevorkyan H, Gonzales CR, James DE, Jhee SS, Komjathy SF, Li L, Lindstrom TD, Mathes BM, Martényi F, Sheehan SM, Stout SL, Timm DE, Vaught GM, Watson BM, Winneroski LL, Yang Z, Mergott DJ. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210. doi: 10.1523/JNEUROSCI.4129-14.2015. PMID: 25609634; PMCID: PMC6605527.

1: May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN, Borders AR, Brier RA, Calligaro DO, Day TA, Ereshefsky L, Erickson JA, Gevorkyan H, Gonzales CR, James DE, Jhee SS, Komjathy SF, Li L, Lindstrom TD, Mathes BM, Martényi F, Sheehan SM, Stout SL, Timm DE, Vaught GM, Watson BM, Winneroski LL, Yang Z, Mergott DJ. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210. doi: 10.1523/JNEUROSCI.4129-14.2015. PubMed PMID: 25609634. 2: Lachno DR, Evert BA, Maloney K, Willis BA, Talbot JA, Vandijck M, Dean RA. Validation and Clinical Utility of ELISA Methods for Quantification of Amyloid-β of Peptides in Cerebrospinal Fluid Specimens from Alzheimer’s Disease Studies. J Alzheimers Dis. 2015;45(2):527-42. PubMed PMID: 25547638. 3: Qi Y, Klyubin I, Harney SC, Hu N, Cullen WK, Grant MK, Steffen J, Wilson EN, Do Carmo S, Remy S, Fuhrmann M, Ashe KH, Cuello AC, Rowan MJ. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents. Acta Neuropathol Commun. 2014 Dec 24;2:175. doi: 10.1186/s40478-014-0175-x. PubMed PMID: 25540024; PubMed Central PMCID: PMC4293804. 4: Lahiri DK, Maloney B, Long JM, Greig NH. Lessons from a BACE1 inhibitor trial: off-site but not off base. Alzheimers Dement. 2014 Oct;10(5 Suppl):S411-9. doi: 10.1016/j.jalz.2013.11.004. Epub 2014 Feb 12. PubMed PMID: 24530026; PubMed Central PMCID: PMC4205206.