Mobocertinib

Summary

Mobocertinib (CHEMBL4650319) is an approved small molecule (ATC L01EB10) targeting EGFR; indicated across 5 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 4 variant-indication associations (e.g. EGFR Exon 20 Insertion in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EB10
• Targets: 1 (EGFR)
• Indications: 5 conditions
• Clinical trials: 12
• Precision-oncology evidence (CIViC): 4 variant–indication associations
• Chemistry: 585.7 Da · C32H39N7O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4650319
Name	Mobocertinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	118607832
ATC	L01EB10
Molecular formula	C32H39N7O4
Molecular weight	585.7
InChIKey	AZSRSNUQCUDCGG-UHFFFAOYSA-N

SMILES: CC(C)OC(=O)C1=CN=C(N=C1C2=CN(C3=CC=CC=C32)C)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC

IUPAC name: propan-2-yl 2-[4-[2-(dimethylamino)ethyl-methylamino]-2-methoxy-5-(prop-2-enoylamino)anilino]-4-(1-methylindol-3-yl)pyrimidine-5-carboxylate

Also known as: AP-32788, AP32788, Mobocertinib, Tak-788, TAK-788, MOBOCERTINIB, US10227342, Example 10, Moboceritinib

Parent form; salt/anhydrous children: CHEMBL4802239

Patent coverage: 412 distinct patent families (929 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 926 (100%) 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	7	17.5%	P00533

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Epidermal growth factor receptor, Epidermal growth factor receptor.

Bioactivity

ChEMBL activities: 18 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	11	IC50	0.01	nM	CHEMBL_ACT_25098086
EGFR	10.7	IC50	0.02	nM	CHEMBL_ACT_29113771
EGFR	10.6	IC50	0.03	nM	CHEMBL_ACT_25098080
EGFR	9	IC50	1	nM	CHEMBL_ACT_25866006
EGFR	8.48	IC50	3.3	nM	CHEMBL_ACT_25018489
EGFR	8.1	IC50	7.94	nM	CHEMBL_ACT_29225394
EGFR	7.7	IC50	19.95	nM	CHEMBL_ACT_29225445
EGFR	7.66	IC50	22	nM	CHEMBL_ACT_25866312
EGFR	7.6	IC50	25	nM	CHEMBL_ACT_25098101
EGFR	7.6	IC50	25.12	nM	CHEMBL_ACT_29225377
EGFR	7.52	IC50	30	nM	CHEMBL_ACT_25866304
EGFR	7.51	IC50	31	nM	CHEMBL_ACT_25018392
EGFR	7.5	IC50	31.62	nM	CHEMBL_ACT_29224923
EGFR	7.47	IC50	34	nM	CHEMBL_ACT_25866190
EGFR	7.46	IC50	34.5	nM	CHEMBL_ACT_25018495
EGFR	7.43	IC50	37	nM	CHEMBL_ACT_25866129
EGFR	6.44	IC50	364	nM	CHEMBL_ACT_25098109
EGFR	6.44	IC50	364	nM	CHEMBL_ACT_29113811

Target pathways

Aggregated over 1 target gene(s): EGFR.

Top Reactome pathways

37 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
PIP3 activates AKT signaling	1	EGFR
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
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Constitutive Signaling by Aberrant PI3K in Cancer	1	EGFR
Signal transduction by L1	1	EGFR
Constitutive Signaling by EGFRvIII	1	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	EGFR
RAF/MAP kinase cascade	1	EGFR
ERBB2 Regulates Cell Motility	1	EGFR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	EGFR
ERBB2 Activates PTK6 Signaling	1	EGFR
Cargo recognition for clathrin-mediated endocytosis	1	EGFR
Clathrin-mediated endocytosis	1	EGFR
PTK6 promotes HIF1A stabilization	1	EGFR
Downregulation of ERBB2 signaling	1	EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	EGFR
Extra-nuclear estrogen signaling	1	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	EGFR

Dominant GO biological processes

GO term	Targets
cell morphogenesis	1
ossification	1
embryonic placenta development	1
positive regulation of protein phosphorylation	1
hair follicle development	1
ubiquitin-dependent protein catabolic process	1
signal transduction	1
cell surface receptor signaling pathway	1
epidermal growth factor receptor signaling pathway	1
salivary gland morphogenesis	1
learning or memory	1
positive regulation of cell population proliferation	1
gene expression	1
protein ubiquitination	1
cerebral cortex cell migration	1

Indications & clinical

Indications

5 indications (1 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	4	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086
lung neoplasm	1	MONDO:0021117	MONDO:0021117

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	8
PHASE3	1
PHASE1/PHASE2	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04129502	PHASE3	ACTIVE_NOT_RECRUITING	TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
NCT02716116	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer
NCT04576208	PHASE2	WITHDRAWN	A Study to Evaluate the Impact of Management Strategies on Gastrointestinal-Related Adverse Events in Participants With Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations Receiving TAK-788
NCT03807778	PHASE1	ACTIVE_NOT_RECRUITING	A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer
NCT03482453	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants
NCT03811834	PHASE1	COMPLETED	A Study to Assess Absolute Bioavailability (ABA) of Mobocertinib (TAK-788) and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of Carbon-14 ([14C])-Mobocertinib in Male Healthy Participants
NCT03928327	PHASE1	COMPLETED	A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants
NCT04051827	PHASE1	COMPLETED	Drug-Drug Interaction Study of TAK-788 and Midazolam in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT04056455	PHASE1	COMPLETED	A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys
NCT04056468	PHASE1	COMPLETED	A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepatic Impairment (HI) and Normal Hepatic Function
NCT04441255	PHASE1	COMPLETED	A Study to Evaluate the Effect of High-Fat Meal on TAK-788 Pharmacokinetics (PK) in Healthy Adult Participants
NCT04535557	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Mobocertinib in Refractory Non-small Cell Lung Cancer (NSCLC) Participants With Epidermal Growth Factor Receptor (EGFR) Exon20 Insertion Mutations

Clinical evidence (CIViC)

Variant × indication × effect (4 predictive associations from 4 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR Exon 20 Insertion	Lung Non-small Cell Carcinoma	Sensitivity/Response	Mobocertinib	CIViC A	EID11228
EGFR Exon 20 Insertion	Lung Non-small Cell Carcinoma	Sensitivity/Response	TAK-788	CIViC B	EID7273
EGFR::ERBB4 Fusion	Lung Adenocarcinoma	Sensitivity/Response	Osimertinib + Mobocertinib + Trastuzumab Deruxtecan + Tarloxotinib	CIViC C	EID12373
EGFR D770_P772dup	Cancer	Sensitivity/Response	Mobocertinib	CIViC D	EID12303

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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR
CHROMIC CHLORIDE	ChEMBL	Phase 4 (approved)	EGFR
CISPLATIN	ChEMBL	Phase 4 (approved)	EGFR
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR
CRIZOTINIB	ChEMBL	Phase 4 (approved)	EGFR
DACOMITINIB	ChEMBL	Phase 4 (approved)	EGFR
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR
DOBUTAMINE	ChEMBL	Phase 4 (approved)	EGFR
DOCETAXEL	ChEMBL	Phase 4 (approved)	EGFR
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR
GEFITINIB	ChEMBL	Phase 4 (approved)	EGFR
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB DITOSYLATE	ChEMBL	Phase 4 (approved)	EGFR
LAZERTINIB	ChEMBL	Phase 4 (approved)	EGFR
LEVODOPA	ChEMBL	Phase 4 (approved)	EGFR
LORLATINIB	ChEMBL	Phase 4 (approved)	EGFR
METHYLDOPA	ChEMBL	Phase 4 (approved)	EGFR
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR
MONTELUKAST	ChEMBL	Phase 4 (approved)	EGFR
NELFINAVIR	ChEMBL	Phase 4 (approved)	EGFR
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR
PERHEXILINE	ChEMBL	Phase 4 (approved)	EGFR
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR
SULOCTIDIL	ChEMBL	Phase 4 (approved)	EGFR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR
TERFENADINE	ChEMBL	Phase 4 (approved)	EGFR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	EGFR
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR
TUCATINIB	ChEMBL	Phase 4 (approved)	EGFR