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Avagacestat (BMS-708163)

Name: Avagacestat (BMS-708163)
Brand: Selleck Chemicals
SKU: S1262
Rating: 5 (21 reviews)

Catalog No.S1262

For research use only.

Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.

Avagacestat (BMS-708163) Chemical Structure

CAS No. 1146699-66-2

Selleck's Avagacestat (BMS-708163) has been cited by 21 publications

Purity & Quality Control

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Download Inhibitor Catalog

Gamma-secretase Signaling Pathway Map

Biological Activity

Description

Features

Appears to be more “notch sparing” than semagacestat (LY450139).

Targets

γ secretase(Aβ42) ^[1] (in H4-8Sw cells)	γ secretase(Aβ40) ^[1] (in H4-8Sw cells)
0.27 nM	0.3 nM

In vitro

BMS-708163 exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

human IMR32 cell	M17z[2Z2dmO2aX;uJIF{e2G7	NYDoNm5MOiCq	MmHJTY5pcWKrdHnvckBw\iCpYX3tZU1{\WO{ZYThd4UhcW5iaIXtZY4hUU2UM{KgZ4VtdCCvZX3idoFv\SC3c3nu[{BCWFBiYYOgd5Vje3S{YYTlJIFnfGW{IEKgbJJ{KGK7IFXMTXNCNCCLQ{WwQVAvOTNibl2=	MYGyN\|MyOjl2NB?=
human H4 cells	Mki2SpVv[3Srb36gZZN{[Xl?		M1Xv[mlvcGmkaYTpc44hd2ZiZ3HtcYEhe2WlcnX0ZZNmNW2nZHnheIVlKGGveXzvbYQh[mW2YUSyJJBzd2S3Y4Tpc44hcW5iaIXtZY4hUDRiY3XscJMh\XiycnXzd4lv\yCqdX3hckBCWFBic4fl[Il{cCCvdYThcpQtKEmFNUC9NE4zOjVizszN	NEn0R\|UzOjR{MEi4OC=>
HEK293 cells	Mlq2SpVv[3Srb36gZZN{[Xl?		NXfrbFR3UW6qaXLpeIlwdiCxZjDnZY1u[S2\|ZXPy[ZRie2ViaX6gTGVMOjl\|IHPlcIx{KGGodHXyJI93\XKwaXfoeEBqdmO3YnH0bY9vKGK7IGfld5Rmem5iYnzveJRqdmdiYX7hcJl{cXNuIFnDOVA:OS5{IH7N	NFn1SYYzOzNzMkm0OC=>
CHO cells	Ml;lSpVv[3Srb36gZZN{[Xl?		NHXwcWtKdmirYnn0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCrbjDDTG8h[2WubIOgZZN{\XO\|ZXSg[ZhxemW\|c3nu[{BCWFCVdzDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIHHtfYxwcWRiYnX0ZUgyKHSxIIipJJNm[3KndHnvckBi\nSncjDveoVzdmmpaISgbY5kfWKjdHnvckBjgSCHTFnTRUwhTUR3ME2xMlIhdk1?	MnPvNlM4OTN4NU[=
human IMR32 cell	MnPlSpVv[3Srb36gZZN{[Xl?	NF\QSXYzKGh?	M3\MXGlvcGmkaYTpc44hd2ZiZ3HtcYEue2WlcnX0ZZNmKGmwIHj1cYFvKEmPUkOyJINmdGxibXXtZpJidmVidYPpcochVm:2Y3igZZMhe3Wkc4TyZZRmKGGodHXyJFIhcHK\|IHL5JGVNUVODLDDJR\|UxRTFwNTDuUS=>	M2K4e\|I{OzF{OUS0
human 786-0 cell	M{DBUGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		M{\S[mlvcGmkaYTpc44hd2ZiaIXtZY4hPzh4LUCgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlMzOTd\|IN88US=>	M{XuZ3NCVkeHUh?=
human NCI-H810 cell	NVHJfZNHT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		M{jLeWlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVi4NVAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjR{NUm4JO69VQ>?	NXHNfGdKW0GQR1XS
human IGR-1 cell	M3TKOWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MmTjTY5pcWKrdHnvckBw\iCqdX3hckBKT1JvMTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG\|c3H5MEBKSzVyPUGuNFQ4PzhizszN	MXPTRW5ITVJ?
human SK-MEL-3 cell	MlLsS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		Mm\LTY5pcWKrdHnvckBw\iCqdX3hckBUUy2PRVytN{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPDl7MkKg{txO	MorPV2FPT0WU
human HT-1080 cell	Mn3FS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NEXVO5dKdmirYnn0bY9vKG:oIHj1cYFvKEiWLUGwPFAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjR6N{[0JO69VQ>?	NHfUWG1USU6JRWK=
human NCI-H23 cell	MUfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		NX31dJdTUW6qaXLpeIlwdiCxZjDoeY1idiCQQ1mtTFI{KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:Oy57M{KyJO69VQ>?	M{LHenNCVkeHUh?=
human Calu-6 cell	MUnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		M3\ZNmlvcGmkaYTpc44hd2ZiaIXtZY4hS2GudT22JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OE46PjBzNDFOwG0>	MoXiV2FPT0WU
human CAPAN-1 cell	MlzOS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NGK3bnpKdmirYnn0bY9vKG:oIHj1cYFvKEODUFHOMVEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF02NjF5OEi2JO69VQ>?	MljRV2FPT0WU
human COLO-668 cell	NWiwOphZT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		NFrzXVdKdmirYnn0bY9vKG:oIHj1cYFvKEORTF:tOlY5KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:PS52MEKyNUDPxE1?	NIrJNW9USU6JRWK=
human TE-6 cell	M1nxWmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NWX3bm5jUW6qaXLpeIlwdiCxZjDoeY1idiCWRT22JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9Ok4yQTB6MjFOwG0>	NXrCd4I4W0GQR1XS
human LCLC-97TM1 cell	M1GzZWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MnfpTY5pcWKrdHnvckBw\iCqdX3hckBNS0yFLUm3WG0yKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OTBwMEi4OkDPxE1?	Ml[2V2FPT0WU
human CAS-1 cell	M{fOTGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NVOxU4tJUW6qaXLpeIlwdiCxZjDoeY1idiCFQWOtNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE{NjZ5MTFOwG0>	NEfMdpZUSU6JRWK=
human RPMI-2650 cell	NUi1RZM4T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MkHETY5pcWKrdHnvckBw\iCqdX3hckBTWE2LLUK2OVAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yOy56MUK0JO69VQ>?	NYPib5JWW0GQR1XS
human MDA-MB-157 cell	M4Lrbmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NX3YZnBxUW6qaXLpeIlwdiCxZjDoeY1idiCPRFGtUWIuOTV5IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTB;MUSuNlQ{OSEQvF2=	MUXTRW5ITVJ?
human KINGS-1 cell	NH\XOItIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NFPrZ\|lKdmirYnn0bY9vKG:oIHj1cYFvKEuLTlfTMVEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yPC5\|N{[yJO69VQ>?	MojaV2FPT0WU
human BB49-HNC cell	MnPuS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MYHJcohq[mm2aX;uJI9nKGi3bXHuJGJDPDlvSF7DJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NVQvPDF\|ODFOwG0>	NYW0VXVRW0GQR1XS
human SK-UT-1 cell	M{XLVmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MXfJcohq[mm2aX;uJI9nKGi3bXHuJHNMNVWWLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xOE43QDh{IN88US=>	Mn7yV2FPT0WU
human EW-11 cell	MmLuS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		M2P0PGlvcGmkaYTpc44hd2ZiaIXtZY4hTVdvMUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xOE45QDN{IN88US=>	M2q3eHNCVkeHUh?=
human D-502MG cell	MljmS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NEPTN5pKdmirYnn0bY9vKG:oIHj1cYFvKERvNUCyUWch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yPC57MEO0JO69VQ>?	M{Txd3NCVkeHUh?=
human MMAC-SF cell	M370Nmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MX;Jcohq[mm2aX;uJI9nKGi3bXHuJG1OSUNvU1[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xOU4xQDN\|IN88US=>	MVXTRW5ITVJ?
human NCI-H1648 cell	NITZTmVIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		MnrnTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEG2OFgh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yPS55N{ig{txO	MlS4V2FPT0WU
human NCI-H292 cell	MmPES5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NY\Gd3FVUW6qaXLpeIlwdiCxZjDoeY1idiCQQ1mtTFI6OiClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxRTF3Lki4NFYh\|ryP	NGLER5RUSU6JRWK=
human NMC-G1 cell	NFLwZ5JIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NHTJdJBKdmirYnn0bY9vKG:oIHj1cYFvKE6PQz3HNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE3NjZ{OUOg{txO	NWrQO3lnW0GQR1XS
human SAS cell	NYf6fJJjT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MV3Jcohq[mm2aX;uJI9nKGi3bXHuJHNCWyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR\|UxRTF5Lke4NVIh\|ryP	NWDBd3lsW0GQR1XS
human HCT-116 cell	MlHES5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		M2WzTmlvcGmkaYTpc44hd2ZiaIXtZY4hUEOWLUGxOkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVE5Njd7NkWg{txO	M{Wyd3NCVkeHUh?=
human SBC-5 cell	NXKwRlZ1T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MYHJcohq[mm2aX;uJI9nKGi3bXHuJHNDSy13IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTB;MUmuNFMh\|ryP	NF33bYhUSU6JRWK=

Click to View More Cell Line Experimental Data

In vivo

Oral administration of BMS-708163 significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. BMS-708163 has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4). ^[1]

Protocol (from reference)

Animal Research:^[1]	Animal Models: Female Harlan Sprague-Dawley rats or ATM-405-142K9 with 7- 10 month old Na?ve, grade II beagles Dosages: 10 mg/kg (rats) or 2.5 mg/kg (dogs) Administration: Dosed daily by oral gavage

References

[1] Gillman KW, et al. Med Chem Lett, 2010, 1 (3), 120–124.

Solubility (25°C)

In vitro	DMSO	104 mg/mL (199.66 mM)
	Water	Insoluble
	Ethanol	Insoluble

Chemical Information

Molecular Weight	520.88
Formula	C₂₀H₁₇ClF₄N₄O₄S
CAS No.	1146699-66-2
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl

Download Avagacestat (BMS-708163) SDF

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01002079	Completed	Drug: BMS-708163\|Drug: Rifampin	Alzheimer Disease	Bristol-Myers Squibb\|PRA Health Sciences	August 2010	Phase 1
NCT01057030	Completed	Drug: BMS-708163\|Drug: Placebo	Alzheimer Disease	Bristol-Myers Squibb	March 2010	Phase 1
NCT01042314	Completed	Drug: Donepezil\|Drug: BMS-708163	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT01039194	Completed	Drug: galantamine\|Drug: BMS-708163	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT00979316	Completed	Drug: BMS-708163\|Drug: Placebo\|Drug: Moxifloxacin	Alzheimer Disease	Bristol-Myers Squibb	September 2009	Phase 1
NCT00890890	Terminated	Drug: Avagacestat\|Drug: Placebo	Alzheimer''s Disease	Bristol-Myers Squibb	May 2009	Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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