Pyrotinib

Summary

Pyrotinib (CHEMBL3647420) is a phase-3 clinical-stage small molecule targeting EGFR and ERBB2; indicated across 8 conditions including non-small cell lung carcinoma and breast neoplasm; with CIViC clinical evidence for 1 variant-indication association (e.g. EGFR::ZNF880 Fusion in her2-receptor positive breast cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (EGFR, ERBB2)
• Indications: 8 conditions
• Clinical trials: 128
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 583.1 Da · C32H31ClN6O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3647420
Name	Pyrotinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	51039030
Molecular formula	C32H31ClN6O3
Molecular weight	583.1
InChIKey	SADXACCFNXBCFY-IYNHSRRRSA-N

SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/[C@H]5CCCN5C

IUPAC name: (E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide

Also known as: Pyrotinib, SHR-1258, PYROTINIB

Patent coverage: 323 distinct patent families (670 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 599 (89%) 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	Irreversible inhibition	7.89	17.5%	P00533
ERBB2	erb-b2 receptor tyrosine kinase 2	Irreversible inhibition	7.42	17.7%	P04626

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor, Tyrosine-protein kinase BTK.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	9.32	IC50	0.48	nM	CHEMBL_ACT_24907895
EGFR	9.01	IC50	0.98	nM	CHEMBL_ACT_24907642
ERBB2	8.62	IC50	2.4	nM	CHEMBL_ACT_24907866
ERBB2	8.41	IC50	3.91	nM	CHEMBL_ACT_24907863
ERBB2	8.35	IC50	4.43	nM	CHEMBL_ACT_24907892
ERBB2	8.18	IC50	6.65	nM	CHEMBL_ACT_24907857
ERBB2	8.04	IC50	9.07	nM	CHEMBL_ACT_24907621
EGFR	7.89	IC50	13	nM	CHEMBL_ACT_17657272
EGFR	7.89	IC50	13	nM	CHEMBL_ACT_17772649
EGFR	7.89	IC50	13	nM	CHEMBL_ACT_26589077
EGFR	7.89	IC50	13	nM	CHEMBL_ACT_29092523
EGFR	7.89	IC50	13	nM	CHEMBL_ACT_29252817
BTK	7.5	IC50	31.7	nM	CHEMBL_ACT_24693368
ERBB2	7.42	IC50	38	nM	CHEMBL_ACT_29092494
EGFR	7.35	IC50	45	nM	CHEMBL_ACT_17772644
ERBB2	7.24	IC50	57.36	nM	CHEMBL_ACT_24907860

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

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
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
breast neoplasm	3	MONDO:0021100	EFO:0003869
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
neoplasm	2	MONDO:0005070	EFO:0000616
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
digestive system neoplasm	2	MONDO:0021223	EFO:0008549
colorectal neoplasm	2	MONDO:0005335	MONDO:0005575

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

Clinical trials

Total trials: 128.

Phase distribution

Phase	Trials
PHASE2	74
Not specified	19
PHASE3	14
PHASE1	8
PHASE1/PHASE2	7
PHASE4	3
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04929548	PHASE4	NOT_YET_RECRUITING	Exploratory Study of Neoadjuvant Treatment of HER2-positive Breast Cancer With Py in Combination With HP
NCT06217185	PHASE4	RECRUITING	The Efficacy and Safety of Pyrotinib, Trastuzumab Combined With Taxanes in the Treatment of Trastuzumab-treated HER2+ Advanced Breast Cancer (ABC).
NCT07600164	PHASE4	NOT_YET_RECRUITING	Real-world Study of Pyrotinib-containing Regimens of Advanced HER2-positive Breast Cancer
NCT04254263	PHASE3	RECRUITING	Adjuvant Study of Pyrotinib in HER-2 Positive Breast Cancer
NCT04290793	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER-2+ Breast Cancer
NCT04736589	PHASE3	NOT_YET_RECRUITING	Inetetamab Plus Rapamycin and Chemotherapy for HER2+ Metastatic Breast Cancer With Abnormal Activation of PAM Pathway
NCT04973319	PHASE3	NOT_YET_RECRUITING	Trastuzumab Combined With Pertuzumab for Adjuvant Treatment of Breast Cancer After Neoadjuvant Therapy
NCT05426486	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients
NCT05841381	PHASE3	NOT_YET_RECRUITING	Adjuvant Study of Pyrotinib in Combination With Trastuzumab in HER2 Positive Invasive Breast Cancer
NCT05910398	PHASE3	RECRUITING	Continuous or Intermittent Extension of Adjuvant Pyrotinib for Invasive HER2-positive Breast Cancer
NCT06144944	PHASE3	ACTIVE_NOT_RECRUITING	Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer
NCT06278870	PHASE3	RECRUITING	Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial
NCT06958627	PHASE2/PHASE3	RECRUITING	The Impact of Intelligent Patient Management Model on Medication Adherence of Pyrotinib Compared to Traditional Patient Management Model: a Prospective, Multicenter, Randomized Controlled Clinical Study
NCT07528716	PHASE3	NOT_YET_RECRUITING	Artificial Intelligence Model-Guided Neoadjuvant Anti-HER2 Targeted Therapy
NCT02973737	PHASE3	UNKNOWN	A Study of Pyrotinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer
NCT03588091	PHASE3	COMPLETED	Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab in Patients With HER2 Positive Breast Cancer
NCT03863223	PHASE3	UNKNOWN	A Study of Pyrotinib in Combination With Trastuzumab and Docetaxel in Patients With HER2 Metastatic Breast Cancer
NCT03980054	PHASE3	UNKNOWN	A Study of Evaluating The Effects Of Pyrotinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer
NCT04447118	PHASE3	COMPLETED	Phase 3 Study of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous NSCLC Harboring a HER2 Exon 20 Mutation Who Failed Platinum Based Chemotherapy
NCT05429684	PHASE3	UNKNOWN	Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer
NCT04126525	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Study of Pyrotinib in HER-2 Positive Breast Cancer
NCT04158856	PHASE2	NOT_YET_RECRUITING	Adjuvant Dual Anti-HER2 Therapy in Patients With Small, Node-negative, HER2-positive Breast Cancer
NCT04398914	PHASE2	ACTIVE_NOT_RECRUITING	Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
NCT04423185	PHASE2	RECRUITING	PLATFORM Study of Precision Medicine for Rare Tumors
NCT04872985	PHASE2	ACTIVE_NOT_RECRUITING	Pyrotinib Plus Neoadjuvant Chemotherapy in HR+/HER2-, HER4-High Breast Cancer
NCT05292742	PHASE2	RECRUITING	Compare Continuation of Original Targeted Therapy With Trastuzumab Combined With Pyrotinib and Capecitabine as Postoperative Adjuvant Therapy in Non-pCR Patients With HER2 Positive Early Breast Cancer
NCT05582499	PHASE2	RECRUITING	Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy
NCT05635487	PHASE2	RECRUITING	A Study of SHR-A1811 Monotherapy or Combined With Pyrotinib Maleate as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients
NCT05638594	PHASE2	RECRUITING	Pyrotinib Combined With Trastuzumab, Dalpiciclib, Letrozole Versus TCbHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HR +/HER2 + Breast Cancer
NCT05751018	PHASE2	RECRUITING	Phase II Clinical Study of Pyrotinib in First-line Treatment of Primary HER2-amplified/Mutated Advanced Non-small Cell Lung Cancer
NCT05769010	PHASE2	RECRUITING	Study of SHR-A1811 in HER2-expression Advanced Breast Cancer With Brain Metastases
NCT05834764	PHASE2	RECRUITING	Pyrotinib in Women With High-risk in Early Stage Breast Cancer
NCT06000917	PHASE2	RECRUITING	A Study of Neoadjuvant TCHpy（Pyrotinib ，Trastuzumab，Carboplatin and Paclitaxel）for ER+/HER2+ Breast Cancer
NCT06001086	PHASE2	RECRUITING	A Phase II Clinical Study of Treatment With Disitamb Vedotin Plus Pyrotinib in HER2-positive Early Breast Cancer
NCT06145308	PHASE2	RECRUITING	Precision Treatment of Recurrent/Metastatic Salivary Gland Carcinoma Guided by Molecular Typing
NCT06185400	PHASE2	NOT_YET_RECRUITING	RC48 Combined With EGFR or HER2 TKI for Locally Advanced or Metastatic NSCLC Patients With HER2 Alterations
NCT06208410	PHASE1/PHASE2	RECRUITING	A Clinical Study of JS105 in Combination With Other Anti-tumor Therapies in Patients With Solid Tumors
NCT06362096	PHASE2	NOT_YET_RECRUITING	A Multicenter, Prospective Study of Diarrhea Tolerance of Pyrotinib Combined With Trastumab and Taxane in the First-line Treatment of HER2-positive Advanced Breast Cancer
NCT06483386	PHASE2	NOT_YET_RECRUITING	Pyrotinib and Subcutaneous Preparation of Trastuzumab Combined With Capecitabine Neoadjuvant Therapy for HER2+ Study of Breast Cancer
NCT06563999	PHASE2	RECRUITING	Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR::ZNF880 Fusion	Her2-receptor Positive Breast Cancer	Sensitivity/Response	Pyrotinib	CIViC C	EID11215

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.

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
REMIBRUTINIB	ChEMBL	Phase 3	EGFR, ERBB2
ZONGERTINIB	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