Pralsetinib

Summary

Pralsetinib (CHEMBL4582651) is an approved small molecule (ATC L01EX23) targeting KDR and RET; indicated across 5 conditions including non-small cell lung carcinoma and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX23
• Targets: 2 (KDR, RET)
• Indications: 5 conditions
• Clinical trials: 13
• Chemistry: 533.6 Da · C27H32FN9O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4582651
Name	Pralsetinib
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	129073603
ATC	L01EX23
Molecular formula	C27H32FN9O2
Molecular weight	533.6
InChIKey	GBLBJPZSROAGMF-SIYOEGHHSA-N

SMILES: CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)N[C@@H](C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC

IUPAC name: N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)-3-pyridinyl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide

Also known as: :pralsetinib, BLU-123244, Blu-667, BLU-667, BLU123244, Cis-pralsetinib, Gavreto, Pralsetinib, cis-, RG-6396, X-581238, X581238

Patent coverage: 612 distinct patent families (1,414 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,387 (98%) 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
KDR	kinase insert domain receptor	Inhibition	7.46	1.1%	P35968
RET	ret proto-oncogene	Inhibition	9.4	0.4%	P07949

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Receptor-type tyrosine-protein kinase FLT3, Proto-oncogene tyrosine-protein kinase receptor Ret, Tyrosine-protein kinase JAK2, Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET.

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
RET	9.52	IC50	0.3	nM	CHEMBL_ACT_25016241
RET	9.52	IC50	0.3	nM	CHEMBL_ACT_29055491
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_25016239
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_25016243
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_25935704
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_29055490
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_29055492
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_29055493
RET	9.15	IC50	0.7	nM	CHEMBL_ACT_23277385
RET	9.11	IC50	0.78	nM	CHEMBL_ACT_23277363
RET	8.71	IC50	1.93	nM	CHEMBL_ACT_23277374
JAK2	8.7	IC50	2	nM	CHEMBL_ACT_23277420
RET	8.62	IC50	2.4	nM	CHEMBL_ACT_25061387
RET	8.57	IC50	2.7	nM	CHEMBL_ACT_29068546
RET	8.46	IC50	3.5	nM	CHEMBL_ACT_29068503
RET	8.38	IC50	4.2	nM	CHEMBL_ACT_29068693
FLT3	8.19	IC50	6.5	nM	CHEMBL_ACT_23277422
RET	6.68	IC50	207.3	nM	CHEMBL_ACT_29068589

Target pathways

Aggregated over 2 target gene(s): KDR, RET.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
Neuropilin interactions with VEGF and VEGFR	1	KDR
VEGF binds to VEGFR leading to receptor dimerization	1	KDR
Integrin cell surface interactions	1	KDR
VEGFA-VEGFR2 Pathway	1	KDR
VEGFR2 mediated cell proliferation	1	KDR
RAF/MAP kinase cascade	1	RET
RET signaling	1	RET
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	KDR
NPAS4 regulates expression of target genes	1	RET
Formation of the nephric duct	1	RET
Formation of the ureteric bud	1	RET
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	KDR

Dominant GO biological processes

GO term	Targets
cell surface receptor protein tyrosine kinase signaling pathway	2
positive regulation of cell migration	2
positive regulation of MAPK cascade	2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
protein phosphorylation	2
angiogenesis	1
ovarian follicle development	1
branching involved in blood vessel morphogenesis	1
vasculogenesis	1
positive regulation of protein phosphorylation	1
positive regulation of endothelial cell proliferation	1
lymph vessel development	1
positive regulation of mesenchymal cell proliferation	1
epithelial cell maturation	1
endocardium development	1

Indications & clinical

Indications

5 indications (4 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	4	MONDO:0005233	EFO:0003060
neoplasm	4	MONDO:0005070	EFO:0000616
thyroid gland carcinoma	2	MONDO:0015075	EFO:0002892

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

Clinical trials

Total trials: 13.

Phase distribution

Phase	Trials
PHASE2	6
Not specified	3
PHASE3	2
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07010393	PHASE4	NOT_YET_RECRUITING	Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
NCT04222972	PHASE3	TERMINATED	A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT04760288	PHASE3	WITHDRAWN	A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
NCT04302025	PHASE2	RECRUITING	A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)
NCT04589845	PHASE2	ACTIVE_NOT_RECRUITING	Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
NCT06482086	PHASE2	RECRUITING	Efficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
NCT06563999	PHASE2	RECRUITING	Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
NCT03037385	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
NCT04591431	PHASE2	UNKNOWN	The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT04632992	PHASE2	COMPLETED	A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response
NCT05525858	Not specified	RECRUITING	KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
NCT07418879	Not specified	NOT_YET_RECRUITING	A Real-world Study of Pralsetinib Combined With Leucogen in the Treatment of RET Fusion-positive NSCLC
NCT04204928	Not specified	APPROVED_FOR_MARKETING	Pre-Approval Access Program (PAAP) for Pralsetinib (BLU-667) in Patients With Unresectable or Metastatic NSCLC or MTC

Clinical evidence (CIViC)

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

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.

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

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
SELPERCATINIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, RET
ALECTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
AXITINIB	ChEMBL	Phase 4 (approved)	KDR, RET
BRIGATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
CABOZANTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
CERITINIB	ChEMBL	Phase 4 (approved)	KDR, RET
DASATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
ENTRECTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
ERLOTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
FEDRATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
IBRUTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
INFIGRATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
LENVATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	KDR, RET
NINTEDANIB	ChEMBL	Phase 4 (approved)	KDR, RET
PONATINIB	ChEMBL	Phase 4 (approved)	KDR, RET
QUIZARTINIB	ChEMBL	Phase 4 (approved)	KDR, RET
SORAFENIB	ChEMBL	Phase 4 (approved)	KDR, RET
SUNITINIB	ChEMBL	Phase 4 (approved)	KDR, RET
TIVOZANIB	ChEMBL	Phase 4 (approved)	KDR, RET
TOFACITINIB	ChEMBL	Phase 4 (approved)	KDR, RET
UPADACITINIB	ChEMBL	Phase 4 (approved)	KDR, RET
VANDETANIB	ChEMBL	Phase 4 (approved)	KDR, RET
VEMURAFENIB	ChEMBL	Phase 4 (approved)	KDR, RET
ALISERTIB	ChEMBL	Phase 3	KDR, RET
BARASERTIB	ChEMBL	Phase 3	KDR, RET
BRIVANIB	ChEMBL	Phase 3	KDR, RET
CANERTINIB	ChEMBL	Phase 3	KDR, RET
CEDIRANIB	ChEMBL	Phase 3	KDR, RET
DEFACTINIB	ChEMBL	Phase 3	KDR, RET
DOVITINIB	ChEMBL	Phase 3	KDR, RET
LESTAURTINIB	ChEMBL	Phase 3	KDR, RET
LINIFANIB	ChEMBL	Phase 3	KDR, RET
MOTESANIB	ChEMBL	Phase 3	KDR, RET
ORANTINIB	ChEMBL	Phase 3	KDR, RET
QUERCETIN	ChEMBL	Phase 3	KDR, RET
RIVOCERANIB	ChEMBL	Phase 3	KDR, RET
SARACATINIB	ChEMBL	Phase 3	KDR, RET
SEMAXANIB	ChEMBL	Phase 3	KDR, RET
VATALANIB	ChEMBL	Phase 3	KDR, RET
AEE-788	ChEMBL	Phase 2	KDR, RET
AT-9283	ChEMBL	Phase 2	KDR, RET
BEMCENTINIB	ChEMBL	Phase 2	KDR, RET
BFH-772	ChEMBL	Phase 2	KDR, RET
BMS-777607	ChEMBL	Phase 2	KDR, RET
CENISERTIB	ChEMBL	Phase 2	KDR, RET
CEP-11981	ChEMBL	Phase 2	KDR, RET
CEP-32496	ChEMBL	Phase 2	KDR, RET
DANUSERTIB	ChEMBL	Phase 2	KDR, RET
DEFOSBARASERTIB	ChEMBL	Phase 2	KDR, RET
DORAMAPIMOD	ChEMBL	Phase 2	KDR, RET
ENMD-2076	ChEMBL	Phase 2	KDR, RET
FGFR INHIBITOR DEBIO 1347	ChEMBL	Phase 2	KDR, RET
FORETINIB	ChEMBL	Phase 2	KDR, RET
GOLVATINIB	ChEMBL	Phase 2	KDR, RET