AT-406

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Search structure


Synonyms	At-406 D-1143 DEBIO 1143 DEBIO-1143 Debio 1143 IAP INHIBITOR AT-406 SM-406 Xevinapant
Status
Molecule Category	UNKNOWN
UNII	N65WC8PXDD
EPA CompTox	DTXSID50648496


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	LSXUTRRVVSPWDZ-MKKUMYSQSA-N
Smiles	CN[C@@H](C)C(=O)N[C@H]1CN(C(=O)CC(C)C)CC[C@H]2CC[C@@H](C(=O)NC(c3ccccc3)c3ccccc3)N2C1=O
InChI	InChI=1S/C32H43N5O4/c1-21(2)19-28(38)36-18-17-25-15-16-27(37(25)32(41)26(20-36)34-30(39)22(3)33-4)31(40)35-29(23-11-7-5-8-12-23)24-13-9-6-10-14-24/h5-14,21-22,25-27,29,33H,15-20H2,1-4H3,(H,34,39)(H,35,40)/t22-,25+,26-,27-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C32H43N5O4
Molecular Weight	561.73
AlogP	2.62
Hydrogen Bond Acceptor	5.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	9.0
Polar Surface Area	110.85
Molecular species	BASE
Aromatic Rings	2.0
Heavy Atoms	41.0

Assay Description	Organism	Bioactivity	Reference
Competitive inhibition of human XIAP BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	225.0 nM		Competitive inhibition of human XIAP BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	66.4 nM
Competitive inhibition of human cIAP1 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	12.3 nM		Competitive inhibition of human cIAP1 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	1.9 nM
Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	22.1 nM		Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	Homo sapiens	5.1 nM
Growth inhibition of human MDA-MB-231 cells after 4 days by WST8 assay	Homo sapiens	144.0 nM
Growth inhibition of human SKOV3 cells after 4 days by WST8 assay	Homo sapiens	142.0 nM
Antagonist activity at XIAP-BIR3 domain (unknown origin) assessed as inhibition of interaction with SMAC at 0.05 uM by fluorescence polarization assay relative to control	Homo sapiens	70.0 %
Antagonist activity at cIAP1-BIR3 domain (unknown origin) assessed as inhibition of interaction with SMAC at 0.01 uM by fluorescence polarization assay relative to control	Homo sapiens	98.0 %
Cytotoxicity against human sensitive EVSA-T cells assessed as inhibition of cell growth after 72 hrs by Alamar Blue assay	Homo sapiens	2.1 nM
Cytotoxicity against human sensitive MDA-MB-231 cells assessed as inhibition of cell growth after 72 hrs by Alamar Blue assay	Homo sapiens	19.0 nM
Antagonist activity at full-length FLAG-tagged XIAP (unknown origin) transfected in HEK293 cells assessed as inhibition of interaction with caspase 9 after 2 hrs by immunoprecipitation assay	Homo sapiens	34.0 nM
Inhibition of N-terminal 6x-His-tagged recombinant human cIAP2-BIR3 (244 to 349 residues) expressed in Escherichia coli incubated for 2 hrs without 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	44.0 nM
Inhibition of N-terminal His-tagged human XIAP-BIR3 (253 to 347 residues) expressed in Escherichia coli BL21-Gold(DE3) pLysS incubated for 2 hrs without 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	42.0 nM
Inhibition of N-terminal His-tagged human XIAP-BIR3 (253 to 347 residues) expressed in Escherichia coli BL21-Gold(DE3) pLysS incubated for 2 hrs after 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	47.8 nM
Inhibition of N-terminal 6x-His-tagged recombinant human cIAP1-BIR3 (258 to 363 residues) expressed in Escherichia coli incubated for 2 hrs without 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	34.0 nM
Inhibition of N-terminal 6x-His-tagged recombinant human cIAP1-BIR3 (258 to 363 residues) expressed in Escherichia coli incubated for 2 hrs after 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	35.0 nM
Inhibition of N-terminal 6x-His-tagged recombinant human cIAP2-BIR3 (244 to 349 residues) expressed in Escherichia coli incubated for 2 hrs after 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA	Homo sapiens	133.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	24.66 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.55 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.55 %

Cross References

Resources	Reference
ChEMBL	CHEMBL2158051
DrugBank	DB16305
FDA SRS	N65WC8PXDD
Guide to Pharmacology	7729
SureChEMBL	SCHEMBL2724374
ZINC	ZINC000043208643

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).