Compound Detail

CHEMBL1090771

AVAGACESTAT

🧪 Phase II

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🧪 Phase II

NC(=O)[C@@H](CCC(F)(F)F)N(Cc1ccc(-c2ncon2)cc1F)S(=O)(=O)c1ccc(Cl)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1090771
Name	AVAGACESTAT
Phase	Phase II
Structure Type	MOL
InChI Key	XEAOPVUAMONVLA-QGZVFWFLSA-N

Known Names

Avagacestat BMS 708163 BMS-708163 BMS-708163-01 BMS-70816301 BMS708163

202

Targets

492

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

520.9

MW (Da)

3.92

ALogP

HBA

HBD

119.4

PSA (Å²)

0.43

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

USAN Stem	-stat
USAN Year	2010

Extended Properties

Molecular Formula	C20H17ClF4N4O4S
MW	520.89
Aromatic Rings	3
Heavy Atoms	34
NP-Likeness	-1.62

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Gamma-secretase inhibitor	INHIBITOR	Gamma-secretase	✓	✓

Indications

Alzheimer Disease

Activity Summary

IC50 492 meas. best 9.89

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Gamma-secretase CHEMBL2094135	IC50	9.89	9.4514	0.1	7
Unchecked CHEMBL612545	IC50	9.52	8.335	0.3	2
786-0 CHEMBL613102	IC50	6.49	6.49	321.7	1
NCI-H810 CHEMBL1075546	IC50	6.37	6.37	426.0	1
IGR-1 CHEMBL1075479	IC50	5.98	5.98	1047.8	1
SK-MEL3 CHEMBL614920	IC50	5.82	5.82	1499.2	1
HT-1080 CHEMBL614580	IC50	5.6	5.6	2487.6	1
NCI-H23 CHEMBL614997	IC50	5.41	5.41	3932.2	1
Calu-6 CHEMBL614535	IC50	5.3	5.3	4960.1	1
CAPAN-1 CHEMBL614536	IC50	5.29	5.29	5178.9	1
COLO-668 CHEMBL2366215	IC50	5.27	5.27	5402.2	1
TE-6 CHEMBL2366144	IC50	5.21	5.21	6190.8	1
LCLC-97TM1 CHEMBL1075489	IC50	5.0	5.0	10088.6	1
RPMI-2650 CHEMBL1075566	IC50	4.86	4.86	13812.4	1
CAS-1 CHEMBL2366100	IC50	4.86	4.86	13671.0	1
MDA-MB-157 CHEMBL1075496	IC50	4.85	4.85	14243.1	1
KINGS-1 CHEMBL2366229	IC50	4.84	4.84	14376.2	1
BB49-HNC CHEMBL2366295	IC50	4.84	4.84	14413.8	1
EW-11 CHEMBL2366223	IC50	4.83	4.83	14883.2	1
SK-UT-1 CHEMBL2366316	IC50	4.83	4.83	14688.2	1
D-502MG CHEMBL2366343	IC50	4.83	4.83	14903.4	1
MMAC-SF CHEMBL2366196	IC50	4.82	4.82	15083.3	1
NCI-H1648 CHEMBL2366214	IC50	4.8	4.8	15778.0	1
NCI-H292 CHEMBL614733	IC50	4.8	4.8	15880.6	1
NMC-G1 CHEMBL2366349	IC50	4.78	4.78	16629.3	1
SAS CHEMBL1075569	IC50	4.75	4.75	17781.2	1
no-10 CHEMBL2366071	IC50	4.73	4.73	18745.2	1
HCT-116 CHEMBL394	IC50	4.73	4.73	18796.5	1
SBC-5 CHEMBL614896	IC50	4.72	4.72	19030.0	1
NCI-H1651 CHEMBL1075519	IC50	4.69	4.69	20304.1	1
NB13 CHEMBL2366225	IC50	4.68	4.68	20825.8	1
ACN CHEMBL2366195	IC50	4.66	4.66	21828.0	1
UACC-62 CHEMBL614610	IC50	4.65	4.65	22195.7	1
COR-L105 CHEMBL1075431	IC50	4.64	4.64	23110.8	1
KGN CHEMBL2366154	IC50	4.64	4.64	22926.8	1
EW-16 CHEMBL2366358	IC50	4.64	4.64	23135.9	1
NUGC-3 CHEMBL614208	IC50	4.64	4.64	23023.1	1
MDA-MB-453 CHEMBL614334	IC50	4.63	4.63	23185.9	1
NCI-H1623 CHEMBL1075517	IC50	4.62	4.62	23811.2	1
NB5 CHEMBL2366328	IC50	4.61	4.61	24475.9	1
8305C CHEMBL1075386	IC50	4.6	4.6	24905.0	1
HPAF-II CHEMBL1075467	IC50	4.6	4.6	25279.4	1
SIMA CHEMBL2366067	IC50	4.59	4.59	25605.1	1
AU565 CHEMBL1075393	IC50	4.58	4.58	25981.9	1
KOSC-2 CHEMBL1075481	IC50	4.58	4.58	26174.9	1
ES7 CHEMBL2366297	IC50	4.58	4.58	26396.0	1
RERF-LC-MS CHEMBL1075563	IC50	4.57	4.57	26877.5	1
SW684 CHEMBL2366143	IC50	4.56	4.56	27725.0	1
NCI-H1975 CHEMBL614348	IC50	4.56	4.56	27450.0	1
RXF 393 CHEMBL614886	IC50	4.56	4.56	27298.9	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1890.83	ng.hr.mL-1	Mus musculus
AUC	2698.21	ng.hr.mL-1	Mus musculus
AUC	12.5	ng.hr.mL-1	Mus musculus
AUC	2733.11	ng.hr.mL-1	Canis lupus familiaris
Cmax	1410.0	nM	Mus musculus
Cmax	2080.0	nM	Mus musculus
Cmax	12.0	nM	Mus musculus
Cmax	881.0	nM	Canis lupus familiaris
Fu	0.01	-	Mus musculus
Fu	0.005	-	Mus musculus
T1/2	40.0	hr	Homo sapiens
Tmax	1.0	hr	Mus musculus
Tmax	1.0	hr	Mus musculus
Tmax	1.0	hr	Mus musculus
Tmax	1.0	hr	Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Gamma-secretase	IC50	=	0.13	nM	9.89	Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-...	23713656
Gamma-secretase	IC50	=	0.13	nM	9.89	Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrat...	23312944
Gamma-secretase	IC50	=	0.225	nM	9.65	Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cel...	22420884
Gamma-secretase	IC50	=	0.27	nM	9.57	Inhibition of gamma-secretase in human H4-8Sw cells assessed as reduction in amy...	29477076
Unchecked	IC50	=	0.3	nM	9.52	Inhibition of gamma-secretase	23046960
Gamma-secretase	IC50	=	0.3	nM	9.52	Inhibition of human gamma secretase-mediated amyloid beta (1 to 40) production e...	19694467
Gamma-secretase	IC50	=	1.5	nM	8.82	Inhibition of partially purified human gamma-secretase-mediated cleavage of notc...	23713656
Gamma-secretase	IC50	=	1.5	nM	8.82	Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substr...	23312944
Unchecked	IC50	=	71.0	nM	7.15	Inhibition of gamma-secretase in CHO cells after overnight incubation by lucifer...	23312944
786-0	IC50	=	321.73	nM	6.49	SANGER: Inhibition of human 786-0 cell growth in a cell viability assay.	-
NCI-H810	IC50	=	425.98	nM	6.37	SANGER: Inhibition of human NCI-H810 cell growth in a cell viability assay.	-
IGR-1	IC50	=	1047.78	nM	5.98	SANGER: Inhibition of human IGR-1 cell growth in a cell viability assay.	-
SK-MEL3	IC50	=	1499.22	nM	5.82	SANGER: Inhibition of human SK-MEL-3 cell growth in a cell viability assay.	-
HT-1080	IC50	=	2487.64	nM	5.6	SANGER: Inhibition of human HT-1080 cell growth in a cell viability assay.	-
NCI-H23	IC50	=	3932.2	nM	5.41	SANGER: Inhibition of human NCI-H23 cell growth in a cell viability assay.	-
Calu-6	IC50	=	4960.14	nM	5.3	SANGER: Inhibition of human Calu-6 cell growth in a cell viability assay.	-
CAPAN-1	IC50	=	5178.86	nM	5.29	SANGER: Inhibition of human CAPAN-1 cell growth in a cell viability assay.	-
COLO-668	IC50	=	5402.21	nM	5.27	SANGER: Inhibition of human COLO-668 cell growth in a cell viability assay.	-
TE-6	IC50	=	6190.82	nM	5.21	SANGER: Inhibition of human TE-6 cell growth in a cell viability assay.	-
LCLC-97TM1	IC50	=	10088.56	nM	5.0	SANGER: Inhibition of human LCLC-97TM1 cell growth in a cell viability assay.	-

Literature References

PubMed	DOI	Target Context	# Activities
22420884	10.1021/jm300094u	ADMET	5
23312944	10.1016/j.bmcl.2012.12.039	Gamma-secretase	4
22420884	10.1021/jm300094u	Mus musculus	4
22420884	10.1021/jm300094u	Plasma	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
23713656	10.1021/jm301741t	Liver microsomes	4
22420884	10.1021/jm300094u	Brain	4
23713656	10.1021/jm301741t	Liver	4
-	10.6019/CHEMBL3301361	ADMET	4
23713656	10.1021/jm301741t	Mus musculus	4
31870650	10.1016/j.bmcl.2019.126856	ADMET	4
19694467	10.1021/jm900188z	Homo sapiens	3
23713656	10.1021/jm301741t	Gamma-secretase	3
22420884	10.1021/jm300094u	No relevant target	3
23713656	10.1021/jm301741t	Unchecked	3
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
29477076	10.1016/j.ejmech.2018.02.035	Gamma-secretase	2
-	10.6019/CHEMBL4651402	SARS-CoV-2	2
19694467	10.1021/jm900188z	Gamma-secretase	2

Data from ChEMBL 36 via Core Engine