Xevinapant

Summary

Xevinapant (CHEMBL2158051) is a phase-3 clinical-stage small molecule targeting XIAP, BIRC2, and BIRC3; indicated across 8 conditions including head and neck squamous cell carcinoma and head and neck cancer.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (XIAP, BIRC2, BIRC3)
• Indications: 8 conditions
• Clinical trials: 10
• Chemistry: 561.7 Da · C32H43N5O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2158051
Name	Xevinapant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	25022340
Molecular formula	C32H43N5O4
Molecular weight	561.7
InChIKey	LSXUTRRVVSPWDZ-MKKUMYSQSA-N

SMILES: C[C@@H](C(=O)N[C@H]1CN(CC[C@H]2CC[C@H](N2C1=O)C(=O)NC(C3=CC=CC=C3)C4=CC=CC=C4)C(=O)CC(C)C)NC

IUPAC name: (5S,8S,10aR)-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-3-(3-methylbutanoyl)-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide

Also known as: At-406, D-1143, Debio 1143, DEBIO-1143, IAP INHIBITOR AT-406, MSC2735845A, SM-406, Xevinapant, SID174006182, XEVINAPANT, AT-406, AT406

Parent form; salt/anhydrous children: CHEMBL2158055

Patent coverage: 246 distinct patent families (680 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
XIAP	X-linked inhibitor of apoptosis	Antagonist	7.18	1.1%	P98170
BIRC2	baculoviral IAP repeat containing 2	Antagonist	8.72	12%	Q13490
BIRC3	baculoviral IAP repeat containing 3	Antagonist	8.29	0.2%	Q13489

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: E3 ubiquitin-protein ligase XIAP, Baculoviral IAP repeat-containing protein 3, Baculoviral IAP repeat-containing protein 2.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BIRC2	8.72	Ki	1.9	nM	CHEMBL_ACT_12070915
BIRC3	8.29	Ki	5.1	nM	CHEMBL_ACT_12070921
BIRC2	7.91	IC50	12.3	nM	CHEMBL_ACT_12070912
BIRC3	7.66	IC50	22.1	nM	CHEMBL_ACT_12070918
XIAP	7.47	EC50	34	nM	CHEMBL_ACT_15671590
BIRC2	7.47	IC50	34	nM	CHEMBL_ACT_19309670
BIRC2	7.46	IC50	35	nM	CHEMBL_ACT_19309665
XIAP	7.38	IC50	42	nM	CHEMBL_ACT_19309690
BIRC3	7.36	IC50	44	nM	CHEMBL_ACT_19309660
XIAP	7.32	IC50	47.8	nM	CHEMBL_ACT_19309685
XIAP	7.18	Ki	66.4	nM	CHEMBL_ACT_12070320
BIRC3	6.88	IC50	133	nM	CHEMBL_ACT_19309655
XIAP	6.65	IC50	225	nM	CHEMBL_ACT_12070317

Target pathways

Aggregated over 3 target gene(s): XIAP, BIRC2, BIRC3.

Top Reactome pathways

40 total, by targets touching each:

Pathway	Targets	Genes
RIPK1-mediated regulated necrosis	3	BIRC2, BIRC3, XIAP
TNFR1-induced proapoptotic signaling	3	BIRC2, BIRC3, XIAP
Regulation of TNFR1 signaling	3	BIRC2, BIRC3, XIAP
TNFR1-induced NF-kappa-B signaling pathway	3	BIRC2, BIRC3, XIAP
Regulation of necroptotic cell death	3	BIRC2, BIRC3, XIAP
Cytokine Signaling in Immune system	2	BIRC2, BIRC3
Signal Transduction	2	BIRC2, BIRC3
Toll Like Receptor 4 (TLR4) Cascade	2	BIRC2, BIRC3
MyD88-independent TLR4 cascade	2	BIRC2, BIRC3
Toll Like Receptor 3 (TLR3) Cascade	2	BIRC2, BIRC3
Innate Immune System	2	BIRC2, BIRC3
Immune System	2	BIRC2, BIRC3
NOD1/2 Signaling Pathway	2	BIRC2, BIRC3
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	2	BIRC2, BIRC3
Toll-like Receptor Cascades	2	BIRC2, BIRC3
TICAM1, RIP1-mediated IKK complex recruitment	2	BIRC2, BIRC3
Metabolism of proteins	2	BIRC2, BIRC3
Regulated Necrosis	2	BIRC2, BIRC3
Programmed Cell Death	2	BIRC2, BIRC3
TNFR2 non-canonical NF-kB pathway	2	BIRC2, BIRC3
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	2	BIRC2, BIRC3
Deubiquitination	2	BIRC2, BIRC3
Ub-specific processing proteases	2	BIRC2, BIRC3
Post-translational protein modification	2	BIRC2, BIRC3
Death Receptor Signaling	2	BIRC2, BIRC3
TNF signaling	2	BIRC2, BIRC3
IKK complex recruitment mediated by RIP1	2	BIRC2, BIRC3
TRIF (TICAM1)-mediated TLR4 signaling	2	BIRC2, BIRC3
Activation of STAT3 by cadherin engagement	2	BIRC2, XIAP
Apoptosis	1	BIRC2

Dominant GO biological processes

GO term	Targets
positive regulation of protein ubiquitination	3
regulation of apoptotic process	3
negative regulation of apoptotic process	3
positive regulation of canonical NF-kappaB signal transduction	3
regulation of innate immune response	3
regulation of inflammatory response	3
regulation of cell cycle	3
regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	3
apoptotic process	3
canonical NF-kappaB signal transduction	3
negative regulation of canonical NF-kappaB signal transduction	2
cell surface receptor signaling pathway	2
tumor necrosis factor-mediated signaling pathway	2
regulation of toll-like receptor signaling pathway	2
non-canonical NF-kappaB signal transduction	2

Indications & clinical

Indications

8 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
head and neck squamous cell carcinoma	3	MONDO:0010150	EFO:0000181
head and neck cancer	3	MONDO:0005627	EFO:0006859
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
lymphoma	1	MONDO:0005062	EFO:0000574
neoplasm	1	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060
glioma	1	MONDO:0021042	MONDO:0100342

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE1	4
PHASE3	2
PHASE2	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05386550	PHASE3	TERMINATED	Phase III Xevinapant (Debio 1143) and Radiotherapy in Resected LA SCCHN, High Risk, Cisplatin-ineligible Participants (XRAY VISION)
NCT05930938	PHASE3	TERMINATED	Study Comparing RT With Cetuximab + Xevinapant to RT With Cetuximab-placebo in Patients With Head and Neck Cancer
NCT04122625	PHASE1/PHASE2	COMPLETED	Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143
NCT05724602	PHASE2	SUSPENDED	Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT06084845	PHASE2	WITHDRAWN	Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer
NCT03270176	PHASE1	COMPLETED	A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy
NCT06056310	PHASE1	TERMINATED	Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)
NCT06110195	PHASE1	TERMINATED	Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer
NCT06463184	PHASE1	WITHDRAWN	Study to Assess Xevinapant in Preoperative Subjects With Recurrent High-Grade Glioma (rHGG)
NCT02022098	Not specified	COMPLETED	Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
BIRINAPANT	ChEMBL	Phase 2	BIRC2, BIRC3, XIAP
LCL-161	ChEMBL	Phase 2	BIRC2, BIRC3, XIAP
Pomalidomide	PubChem	Approved	BIRC2, BIRC3, XIAP
PHENYLALANINE	ChEMBL	Phase 3	XIAP