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Compound Detail

CHEMBL2158051

XEVINAPANT
🧪 Phase III
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🧪 Phase III
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

Basic Information

ChEMBL ID CHEMBL2158051
Name XEVINAPANT
Phase Phase III
Structure Type MOL
InChI Key LSXUTRRVVSPWDZ-MKKUMYSQSA-N

Known Names

At-406 D-1143 Debio 1143 DEBIO-1143 IAP INHIBITOR AT-406 MSC2735845A SM-406 Xevinapant
7
Targets
20
Activities
4
Assay Types
30
PK Parameters
20
Publications
8
Known Names
8
Indications

Molecular Properties

561.7
MW (Da)
2.62
ALogP
5
HBA
3
HBD
110.8
PSA (Ų)
0.44
QED
1
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -napant; -vin-
USAN Year 2022

Extended Properties

Molecular Formula C32H43N5O4
MW 561.73
Aromatic Rings 2
Heavy Atoms 41
NP-Likeness -0.74

Indications

Carcinoma, Squamous Cell Head and Neck Neoplasms Carcinoma, Non-Small-Cell Lung Glioma Leukemia, Myeloid, Acute Lymphoma Neoplasms Neoplasms

Activity Summary

IC50 12 meas. best 7.91
Ki 4 meas. best 8.72
EC50 3 meas. best 8.68
Kd 1 meas. best 5.05

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Baculoviral IAP repeat-containing protein 2
CHEMBL5462
Ki 8.72 8.72 1.9 1
EVSA-T
CHEMBL614295
EC50 8.68 8.68 2.1 1
Baculoviral IAP repeat-containing protein 3
CHEMBL5335
Ki 8.29 8.29 5.1 1
Baculoviral IAP repeat-containing protein 2
CHEMBL5462
IC50 7.91 7.6133 12.3 3
MDA-MB-231
CHEMBL400
EC50 7.72 7.72 19.0 1
Baculoviral IAP repeat-containing protein 3
CHEMBL5335
IC50 7.66 7.3 22.1 3
E3 ubiquitin-protein ligase XIAP
CHEMBL4198
EC50 7.47 7.47 34.0 1
E3 ubiquitin-protein ligase XIAP
CHEMBL4198
IC50 7.38 7.1167 42.0 3
E3 ubiquitin-protein ligase XIAP
CHEMBL4198
Ki 7.18 7.18 66.4 1
SK-OV-3
CHEMBL614925
IC50 6.85 6.85 142.0 1
MDA-MB-231
CHEMBL400
IC50 6.84 6.84 144.0 1
Nonstructural protein 3
CHEMBL4523954
IC50 5.39 5.39 4100.0 1
Nonstructural protein 3
CHEMBL4523954
Kd 5.05 5.05 9000.0 1
Nonstructural protein 3
CHEMBL4523954
Ki 4.87 4.87 13500.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 3800.0 ng.hr.mL-1 Mus musculus
AUC 1200.0 ng.hr.mL-1 Mus musculus
AUC 4300.0 ng.hr.mL-1 Mus musculus
AUC 17400.0 ng.hr.mL-1 Mus musculus
AUC 8300.0 ng.hr.mL-1 Mus musculus
AUC 1100.0 ng.hr.mL-1 Mus musculus
AUC 9600.0 ng.hr.mL-1 Mus musculus
AUC 57300.0 ng.hr.mL-1 Mus musculus
CL 16.98 uL.min-1.(10^6cells)-1 Rattus norvegicus
Cmax 5340.64 nM Mus musculus
Cmax 1602.19 nM Mus musculus
Cmax 2136.26 nM Mus musculus
Cmax 10503.27 nM Mus musculus
Cmax 6408.77 nM Mus musculus
Cmax 462.86 nM Mus musculus
Cmax 4272.52 nM Mus musculus
Cmax 19226.32 nM Mus musculus
F 31.0 % Mus musculus
F 38.0 % Mus musculus
F 46.0 % Mus musculus
T1/2 3.0 hr Mus musculus
T1/2 2.4 hr Mus musculus
T1/2 2.3 hr Mus musculus
T1/2 5.4 hr Mus musculus
Tmax 1.0 hr Mus musculus
Tmax 2.0 hr Mus musculus
Tmax 0.25 hr Mus musculus
Tmax 0.25 hr Mus musculus
Tmax 1.0 hr Mus musculus
Tmax 2.0 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Baculoviral IAP repeat-containing protein 2 Ki = 1.9 nM 8.72 Competitive inhibition of human cIAP1 BIR3 domain expressed in Escherichia coli ... 21443232
EVSA-T EC50 = 2.1 nM 8.68 Cytotoxicity against human sensitive EVSA-T cells assessed as inhibition of cell... 26218264
Baculoviral IAP repeat-containing protein 3 Ki = 5.1 nM 8.29 Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli ... 21443232
Baculoviral IAP repeat-containing protein 2 IC50 = 12.3 nM 7.91 Competitive inhibition of human cIAP1 BIR3 domain expressed in Escherichia coli ... 21443232
MDA-MB-231 EC50 = 19.0 nM 7.72 Cytotoxicity against human sensitive MDA-MB-231 cells assessed as inhibition of ... 26218264
Baculoviral IAP repeat-containing protein 3 IC50 = 22.1 nM 7.66 Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli ... 21443232
E3 ubiquitin-protein ligase XIAP EC50 = 34.0 nM 7.47 Antagonist activity at full-length FLAG-tagged XIAP (unknown origin) transfected... 26218264
Baculoviral IAP repeat-containing protein 2 IC50 = 34.0 nM 7.47 Inhibition of N-terminal 6x-His-tagged recombinant human cIAP1-BIR3 (258 to 363 ... 31550155
Baculoviral IAP repeat-containing protein 2 IC50 = 35.0 nM 7.46 Inhibition of N-terminal 6x-His-tagged recombinant human cIAP1-BIR3 (258 to 363 ... 31550155
E3 ubiquitin-protein ligase XIAP IC50 = 42.0 nM 7.38 Inhibition of N-terminal His-tagged human XIAP-BIR3 (253 to 347 residues) expres... 31550155
Baculoviral IAP repeat-containing protein 3 IC50 = 44.0 nM 7.36 Inhibition of N-terminal 6x-His-tagged recombinant human cIAP2-BIR3 (244 to 349 ... 31550155
E3 ubiquitin-protein ligase XIAP IC50 = 47.8 nM 7.32 Inhibition of N-terminal His-tagged human XIAP-BIR3 (253 to 347 residues) expres... 31550155
E3 ubiquitin-protein ligase XIAP Ki = 66.4 nM 7.18 Competitive inhibition of human XIAP BIR3 domain expressed in Escherichia coli B... 21443232
Baculoviral IAP repeat-containing protein 3 IC50 = 133.0 nM 6.88 Inhibition of N-terminal 6x-His-tagged recombinant human cIAP2-BIR3 (244 to 349 ... 31550155
SK-OV-3 IC50 = 142.0 nM 6.85 Growth inhibition of human SKOV3 cells after 4 days by WST8 assay 21443232
MDA-MB-231 IC50 = 144.0 nM 6.84 Growth inhibition of human MDA-MB-231 cells after 4 days by WST8 assay 21443232
E3 ubiquitin-protein ligase XIAP IC50 = 225.0 nM 6.65 Competitive inhibition of human XIAP BIR3 domain expressed in Escherichia coli B... 21443232
Nonstructural protein 3 IC50 = 4100.0 nM 5.39 Inhibition of N-terminal His-tagged Zika virus NS2B-NS3 protease (1 to 187 resid... 31980339
Nonstructural protein 3 Kd = 9000.0 nM 5.05 Binding affinity to N-terminal His-tagged Zika virus NS2B-NS3 protease (1 to 187... 31980339
Nonstructural protein 3 Ki = 13500.0 nM 4.87 Inhibition of N-terminal His-tagged Zika virus NS2B-NS3 protease (1 to 187 resid... 31980339

Literature References

PubMed DOI Target Context # Activities
21443232 10.1021/jm101505d Plasma 18
21443232 10.1021/jm101505d ADMET 15
21443232 10.1021/jm101505d MDA-MB-231 11
- 10.6019/CHEMBL5303304 Fibroblast 8
- 10.6019/CHEMBL5303304 HEK-293T 6
31550155 10.1021/acs.jmedchem.9b01108 E3 ubiquitin-protein ligase XIAP 5
21443232 10.1021/jm101505d Baculoviral IAP repeat-containing protein 2 4
31550155 10.1021/acs.jmedchem.9b01108 Baculoviral IAP repeat-containing protein 3 4
31550155 10.1021/acs.jmedchem.9b01108 Baculoviral IAP repeat-containing protein 2 4
31980339 10.1016/j.bmcl.2020.126965 Nonstructural protein 3 3
31550155 10.1021/acs.jmedchem.9b01108 A549 3
31550155 10.1021/acs.jmedchem.9b01108 SK-MEL-28 3
21443232 10.1021/jm101505d E3 ubiquitin-protein ligase XIAP 3
21443232 10.1021/jm101505d Baculoviral IAP repeat-containing protein 3 2
- 10.6019/CHEMBL3301361 ADMET 2
26218264 10.1021/acs.jmedchem.5b00706 E3 ubiquitin-protein ligase XIAP 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
26218264 10.1021/acs.jmedchem.5b00706 MDA-MB-231 2
21443232 10.1021/jm101505d No relevant target 1
- 10.6019/CHEMBL5308504 Bromodomain-containing protein 4 1

Data from ChEMBL 36 via Core Engine