Zongertinib

Summary

Zongertinib (CHEMBL5314498) is a phase-3 clinical-stage small molecule targeting EGFR and ERBB2; indicated across 1 condition including neoplasm; with CIViC clinical evidence for 3 variant-indication associations (e.g. ERBB2 A775_G776insYVMA in lung non-small cell carcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (EGFR, ERBB2)
• Indications: 1 condition
• Clinical trials: 12
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 535.6 Da · C29H29N9O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5314498
Name	Zongertinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	160283094
Molecular formula	C29H29N9O2
Molecular weight	535.6
InChIKey	YSGNGFPNTLERCR-UHFFFAOYSA-N

SMILES: CC1=C(C=CC(=C1)NC2=NC=NC3=CN=C(N=C32)N4CCC(CC4)NC(=O)C=C)OC5=CC6=C(C=C5)N(C=N6)C

IUPAC name: N-[1-[4-[3-methyl-4-(1-methylbenzimidazol-5-yl)oxyanilino]pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-yl]prop-2-enamide

Also known as: BI 1810631, BI-1810631, BI1810631, Zongertinib, ZONGERTINIB

Patent coverage: 11 distinct patent families (15 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 10 (67%) of the total. 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
EGFR	epidermal growth factor receptor	Inhibition	6.24	17.5%	P00533
ERBB2	erb-b2 receptor tyrosine kinase 2	Inhibition	7.89	17.7%	P04626

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ERBB2	7.89	IC50	13	nM	CHEMBL_ACT_29092487
EGFR	6.24	IC50	579	nM	CHEMBL_ACT_29092519

Target pathways

Aggregated over 2 target gene(s): EGFR, ERBB2.

Top Reactome pathways

53 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	2	EGFR, ERBB2
SHC1 events in ERBB2 signaling	2	EGFR, ERBB2
PLCG1 events in ERBB2 signaling	2	EGFR, ERBB2
PIP3 activates AKT signaling	2	EGFR, ERBB2
GRB2 events in ERBB2 signaling	2	EGFR, ERBB2
PI3K events in ERBB2 signaling	2	EGFR, ERBB2
Constitutive Signaling by Aberrant PI3K in Cancer	2	EGFR, ERBB2
RAF/MAP kinase cascade	2	EGFR, ERBB2
ERBB2 Regulates Cell Motility	2	EGFR, ERBB2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	EGFR, ERBB2
ERBB2 Activates PTK6 Signaling	2	EGFR, ERBB2
Downregulation of ERBB2 signaling	2	EGFR, ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	EGFR, ERBB2
Signaling by ERBB2 KD Mutants	2	EGFR, ERBB2
Signaling by ERBB2 ECD mutants	2	EGFR, ERBB2
Signaling by ERBB2 TMD/JMD mutants	2	EGFR, ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	EGFR, ERBB2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
GRB7 events in ERBB2 signaling	1	ERBB2
Downregulation of ERBB2:ERBB3 signaling	1	ERBB2
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Sema4D induced cell migration and growth-cone collapse	1	ERBB2
Signal transduction by L1	1	EGFR

Dominant GO biological processes

GO term	Targets
signal transduction	2
cell surface receptor signaling pathway	2
epidermal growth factor receptor signaling pathway	2
neuron differentiation	2
positive regulation of cell growth	2
ERBB2-EGFR signaling pathway	2
negative regulation of apoptotic process	2
positive regulation of MAPK cascade	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
positive regulation of epithelial cell proliferation	2
cellular response to epidermal growth factor stimulus	2
protein phosphorylation	2
cell surface receptor protein tyrosine kinase signaling pathway	2
cell population proliferation	2
regulation of cell population proliferation	2

Indications & clinical

Indications

1 indication (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
neoplasm	1	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	7
PHASE3	2
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06151574	PHASE3	ACTIVE_NOT_RECRUITING	Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment
NCT07195695	PHASE3	RECRUITING	Beamion LUNG-3: Adjuvant Zongertinib vs Standard Treatment in People With Completely Resected Stage II-IIIB NSCLC Harboring Activating HER2 TKD Mutations
NCT06324357	PHASE1/PHASE2	RECRUITING	Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
NCT06581432	PHASE2	RECRUITING	Beamion PANTUMOR-1: A Study to Test Whether Zongertinib Helps People With Advanced Cancers With HER2 Alterations
NCT07486817	PHASE2	NOT_YET_RECRUITING	Beamion 44: A Study to Test How Well Zongertinib is Tolerated by People With Advanced Non-small Cell Lung Cancer With HER2 Mutations When Given in Combination With Chemotherapy With or Without Pembrolizumab
NCT04886804	PHASE1	ACTIVE_NOT_RECRUITING	Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)
NCT05833139	PHASE1	COMPLETED	A Study in Healthy Men to Test How Itraconazole Influences the Amount of Zongertinib (BI 1810631) in the Blood
NCT05879991	PHASE1	COMPLETED	A Study in Healthy Men to Test How Zongertinib (BI 1810631) is Taken up and Processed by the Body
NCT06028464	PHASE1	COMPLETED	A Study in Healthy Men to Test Whether Carbamazepine Influences the Amount of Zongertinib in the Blood
NCT06075277	PHASE1	COMPLETED	A Study in Healthy Men to Test How Zongertinib is Taken up in the Body When Taken With or Without Food
NCT06494761	PHASE1	COMPLETED	A Study in Healthy Men to Test Whether Zongertinib Affects How 3 Other Medicines (Midazolam, Omeprazole, and Repaglinide) Are Taken up and Processed by the Body
NCT06504862	PHASE1	COMPLETED	A Study in Healthy Men to Test Whether Zongertinib Influences the Amount of 4 Other Medicines (Dabigatran, Rosuvastatin, Metformin, and Furosemide) in the Blood

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
ERBB2 A775_G776insYVMA	Lung Non-small Cell Carcinoma	Sensitivity/Response	Zongertinib	CIViC A	EID12564
ERBB2 L755P OR ERBB2 G776V OR ERBB2 G776delinsVC OR ERBB2 P780_Y781insGSP	Lung Non-small Cell Carcinoma	Sensitivity/Response	Zongertinib	CIViC A	EID12563
ERBB2 Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Zongertinib	CIViC A	EID12530

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

171 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB DITOSYLATE	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAZERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TUCATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ZANUBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ALISERTIB	ChEMBL	Phase 3	EGFR, ERBB2
ALVOCIDIB	ChEMBL	Phase 3	EGFR, ERBB2
CANDESARTAN	ChEMBL	Phase 3	EGFR, ERBB2
CANERTINIB	ChEMBL	Phase 3	EGFR, ERBB2
CEDIRANIB	ChEMBL	Phase 3	EGFR, ERBB2
ENCLOMIPHENE	ChEMBL	Phase 3	EGFR, ERBB2
MASITINIB	ChEMBL	Phase 3	EGFR, ERBB2
POZIOTINIB	ChEMBL	Phase 3	EGFR, ERBB2
PYROTINIB	ChEMBL	Phase 3	EGFR, ERBB2
REMIBRUTINIB	ChEMBL	Phase 3	EGFR, ERBB2
AEE-788	ChEMBL	Phase 2	EGFR, ERBB2
ALLITINIB	ChEMBL	Phase 2	EGFR, ERBB2
ATUZABRUTINIB	ChEMBL	Phase 2	EGFR, ERBB2
CENISERTIB	ChEMBL	Phase 2	EGFR, ERBB2
CLOSANTEL	ChEMBL	Phase 2	EGFR, ERBB2
CP-724714	ChEMBL	Phase 2	EGFR, ERBB2
DEFOSBARASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
ELLAGIC ACID	ChEMBL	Phase 2	EGFR, ERBB2
FALNIDAMOL	ChEMBL	Phase 2	EGFR, ERBB2
FORETINIB	ChEMBL	Phase 2	EGFR, ERBB2
ILORASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
IODOQUINOL	ChEMBL	Phase 2	EGFR, ERBB2