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Zanzalintinib

drug
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Also known as Xl 092XL-092XL092

Summary

Zanzalintinib (CHEMBL5314428) is a phase-3 clinical-stage small molecule targeting MET, AXL, and MERTK; indicated across 7 conditions including renal cell carcinoma and clear cell renal carcinoma.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 3 (MET, AXL, MERTK)
  • Indications: 7 conditions
  • Clinical trials: 40
  • Chemistry: 528.5 Da · C29H25FN4O5

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL5314428
NameZanzalintinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID139350422
Molecular formulaC29H25FN4O5
Molecular weight528.5
InChIKeyJSPCKALGNNVYOO-UHFFFAOYSA-N

SMILES: CNC(=O)C1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F

IUPAC name: 1-N’-(4-fluorophenyl)-1-N-[4-[7-methoxy-6-(methylcarbamoyl)quinolin-4-yl]oxyphenyl]cyclopropane-1,1-dicarboxamide

Also known as: Xl 092, XL-092, XL092, Zanzalintinib, ZANZALINTINIB

Parent form; salt/anhydrous children: CHEMBL5314605

Patent coverage: 67 distinct patent families (191 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 149 (78%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
METMET proto-oncogene, receptor tyrosine kinaseInhibition82.4%P08581
AXLAXL receptor tyrosine kinaseInhibition81.1%P30530
MERTKMER proto-oncogene, tyrosine kinaseInhibition80.6%Q12866

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Tyrosine-protein kinase receptor UFO.

Bioactivity

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

TargetpChemblTypeValueUnitActivity ID
AXL8.24IC505.8nMCHEMBL_ACT_25838256

Target pathways

Aggregated over 3 target gene(s): MET, AXL, MERTK.

Top Reactome pathways

48 total, by targets touching each:

PathwayTargetsGenes
Dengue Virus Attachment and Entry2AXL, MERTK
Hemostasis1MERTK
PIP3 activates AKT signaling1MET
Developmental Biology1MET
Signal Transduction1MET
Disease1MET
Negative regulation of the PI3K/AKT network1MET
Cell surface interactions at the vascular wall1MERTK
Generic Transcription Pathway1MET
PI3K/AKT Signaling in Cancer1MET
Constitutive Signaling by Aberrant PI3K in Cancer1MET
Semaphorin interactions1MET
Sema4D in semaphorin signaling1MET
Sema4D mediated inhibition of cell attachment and migration1MET
Axon guidance1MET
VEGFA-VEGFR2 Pathway1AXL
Diseases of signal transduction by growth factor receptors and second messengers1MET
Infectious disease1MET
RAF/MAP kinase cascade1MET
MAPK family signaling cascades1MET
MAPK1/MAPK3 signaling1MET
Signaling by MET1MET
MET Receptor Activation1MET
Negative regulation of MET activity1MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling1MET
RNA Polymerase II Transcription1MET
Gene expression (Transcription)1MET
MET activates RAS signaling1MET
MET activates PI3K/AKT signaling1MET
MET activates PTPN111MET

Dominant GO biological processes

GO termTargets
cell surface receptor protein tyrosine kinase signaling pathway3
protein phosphorylation3
cell surface receptor signaling pathway2
signal transduction2
natural killer cell differentiation2
phagocytosis2
spermatogenesis2
nervous system development2
cell migration2
platelet activation2
secretion by cell2
substrate adhesion-dependent cell spreading2
negative regulation of lymphocyte activation2
establishment of localization in cell2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction2

Indications & clinical

Indications

7 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).

IndicationTrial phaseMONDOEFO
renal cell carcinoma3MONDO:0005086EFO:0000681
clear cell renal carcinoma3MONDO:0005005EFO:0000349
renal cell adenocarcinoma3MONDO:0005549EFO:0005708
colorectal neoplasm3MONDO:0005335MONDO:0005575
neoplasm2MONDO:0005070EFO:0000616
head and neck squamous cell carcinoma2MONDO:0010150EFO:0000181
non-small cell lung carcinoma1MONDO:0005233EFO:0003060

Clinical trials

Total trials: 40.

Phase distribution

PhaseTrials
PHASE221
PHASE19
PHASE34
PHASE1/PHASE24
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05425940PHASE3ACTIVE_NOT_RECRUITINGStudy of XL092 + Atezolizumab vs Regorafenib in Participants With Metastatic Colorectal Cancer
NCT05678673PHASE3ACTIVE_NOT_RECRUITINGStudy of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
NCT06082167PHASE2/PHASE3ACTIVE_NOT_RECRUITINGStudy of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
NCT06943755PHASE2/PHASE3RECRUITINGZanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors
NCT07227402PHASE3RECRUITINGA Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)
NCT07489495PHASE3RECRUITINGA Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)
NCT06568562PHASE2RECRUITINGXL092 in Patients With Metastatic Castration-Resistant Prostate Cancer
NCT06571734PHASE2RECRUITINGXL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma
NCT06698250PHASE2RECRUITINGZanzalintinib (XL-092) Plus Durvalumab and Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)
NCT06794229PHASE2RECRUITINGNeoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis
NCT06863311PHASE2RECRUITINGTrial of Zanzalintinib (XL092) in Combination With Immunotherapy in Patients Who Progress on Adjuvant Therapy in Clear Cell RCC
NCT06926634PHASE2RECRUITINGZanzalintinib Maintenance in Patients With High Grade Neuroendocrine Neoplasms (HG-NENs)
NCT06937866PHASE1/PHASE2RECRUITINGMaintenance Zanzalintinib With Etoposide After HDCT in GCT
NCT06959511PHASE2RECRUITINGZanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery
NCT06959641PHASE2RECRUITINGXL092 for the Treatment of Locally Advanced or Metastatic Radioiodine Refractory Differentiated Thyroid Cancer
NCT07042919PHASE1/PHASE2NOT_YET_RECRUITINGZanzalintinib in Second Line and Beyond for the Treatment of Advanced Liver Cancer
NCT07043608PHASE2NOT_YET_RECRUITINGZanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases
NCT07049926PHASE1/PHASE2RECRUITINGSubstudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (MK-3475-03C/KEYMAKER-U03)
NCT07185945PHASE2NOT_YET_RECRUITINGZanzalintinib for Advanced Urothelial Carcinoma Progressing After Prior Therapy
NCT07193550PHASE2RECRUITINGA Phase 2 Trial of Zanzalintinib in Advanced/Metastatic Bone Sarcomas (ZAMBONE)
NCT07218666PHASE2NOT_YET_RECRUITINGZanzalintinib in Men With Aggressive Variant Prostate Cancer
NCT07226063PHASE2NOT_YET_RECRUITINGMaintenance Zanzalintinib and Durvalumab in Participants With Advanced Hepatocellular Cancer
NCT07283731PHASE2RECRUITINGPhase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma
NCT07428616PHASE2RECRUITINGA Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07470489PHASE2NOT_YET_RECRUITINGZanzalintinib Plus Cemiplimab for the Treatment of BRAF Wild-Type Anaplastic Thyroid Cancer
NCT07484139PHASE2NOT_YET_RECRUITINGH&N NEO-COMBAT XL: Neoadjuvant XL-092 (Zanzalintinib) and Pembrolizumab (Keytruda) in Surgically Resectable, HPV Negative Oral Cavity Squamous Cell Carcinoma (OCSCC)
NCT07511504PHASE2NOT_YET_RECRUITINGY-90 Radioembolization, Durvalumab, Tremelimumab, and Zanzalintinib for the Treatment of Unresectable and Locally-Advanced Hepatocellular Carcinoma
NCT07527169PHASE2NOT_YET_RECRUITINGA Phase 2 Study Of Zanzalintinib For Patients With Recurrent Or Metastatic Olfactory Neuroblastoma
NCT07578025PHASE2NOT_YET_RECRUITINGZanzalintinib and MO-03 for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy
NCT07608718PHASE2NOT_YET_RECRUITINGPhase II Trial of Zanzalitinib in Patients With Metastatic Castration Resistant Prostate Cancer
NCT03337698PHASE1/PHASE2TERMINATEDA Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
NCT03845166PHASE1ACTIVE_NOT_RECRUITINGA Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors
NCT05176483PHASE1RECRUITINGStudy of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors
NCT06795009PHASE1RECRUITINGZanzalintinib in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer
NCT06902376PHASE1RECRUITINGXL092 and Cemiplimab in BRAF WT Thyroid Cancer
NCT06912087PHASE1RECRUITINGDose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC
NCT06957431PHASE1RECRUITINGZanzalintinib Combined With Eribulin in Advanced Liposarcoma and Leiomyosarcoma
NCT06962332PHASE1RECRUITINGPharmacokinetics (PK) and Safety of Zanzalintinib in Participants With Moderate Hepatic Impairment (HI)
NCT06968988PHASE1RECRUITINGZanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma
NCT06191796PHASE1TERMINATEDStudy of Zanzalintinib (XL092) + AB521 and Zanzalintinib + AB521 + Nivolumab in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Other Advanced Solid Tumors (STELLAR-009)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
ERLOTINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
FEDRATINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
GEFITINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
PAZOPANIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
SORAFENIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK, MET
AXITINIBChEMBLPhase 4 (approved)AXL, MERTK, MET
BOSUTINIBChEMBLPhase 4 (approved)AXL, MERTK, MET
CABOZANTINIBChEMBLPhase 4 (approved)AXL, MERTK, MET
MIDOSTAURINChEMBLPhase 4 (approved)AXL, MERTK, MET
NERATINIBChEMBLPhase 4 (approved)AXL, MERTK, MET
NINTEDANIBChEMBLPhase 4 (approved)AXL, MERTK, MET
SUNITINIBChEMBLPhase 4 (approved)AXL, MERTK, MET
VANDETANIBChEMBLPhase 4 (approved)AXL, MERTK, MET
CEDIRANIBChEMBLPhase 3AXL, MERTK, MET
LESTAURTINIBChEMBLPhase 3AXL, MERTK, MET
LINIFANIBChEMBLPhase 3AXL, MERTK, MET
BEMCENTINIBChEMBLPhase 2AXL, MERTK, MET
BMS-754807ChEMBLPhase 2AXL, MERTK, MET
BMS-777607ChEMBLPhase 2AXL, MERTK, MET
FORETINIBChEMBLPhase 2AXL, MERTK, MET
GLESATINIBChEMBLPhase 2AXL, MERTK, MET
MERESTINIBChEMBLPhase 2AXL, MERTK, MET
PELITINIBChEMBLPhase 2AXL, MERTK, MET
R-406ChEMBLPhase 2AXL, MERTK, MET
REBASTINIBChEMBLPhase 2AXL, MERTK, MET
SU-014813ChEMBLPhase 2AXL, MERTK, MET
TOZASERTIBChEMBLPhase 2AXL, MERTK, MET
IdelalisibPubChemApprovedAXL, MERTK, MET
SelumetinibPubChemApprovedAXL, MERTK, MET
QUIZARTINIBChEMBL + PubChemPhase 4 (approved)AXL, MERTK
ENTRECTINIBChEMBLPhase 4 (approved)AXL, MET
ALVOCIDIBChEMBLPhase 3AXL, MERTK
CANERTINIBChEMBLPhase 3AXL, MET
DOVITINIBChEMBLPhase 3AXL, MERTK
ENZASTAURINChEMBLPhase 3AXL, MET
ITACITINIBChEMBLPhase 3AXL, MERTK
POVORCITINIBChEMBLPhase 3AXL, MERTK
QUERCETINChEMBLPhase 3AXL, MET
SITRAVATINIBChEMBLPhase 3AXL, MET
AT-9283ChEMBLPhase 2MERTK, MET
BI-2536ChEMBLPhase 2MERTK, MET
CENISERTIBChEMBLPhase 2AXL, MET
DALMELITINIBChEMBLPhase 2AXL, MET
DEFOSBARASERTIBChEMBLPhase 2AXL, MET
ILORASERTIBChEMBLPhase 2AXL, MET
MK-2461ChEMBLPhase 2MERTK, MET
NINGETINIBChEMBLPhase 2AXL, MET
OSI-632ChEMBLPhase 2AXL, MET
TAMNORZATINIBChEMBLPhase 2AXL, MERTK
TANDUTINIBChEMBLPhase 2AXL, MERTK
BinimetinibPubChemApprovedMERTK, MET
TrametinibPubChemApprovedAXL, MET
AFATINIB DIMALEATEChEMBLPhase 4 (approved)MET
BRIGATINIBChEMBLPhase 4 (approved)MET
CABOZANTINIB S-MALATEChEMBLPhase 4 (approved)MET
CAPMATINIBChEMBLPhase 4 (approved)MET
CERITINIBChEMBLPhase 4 (approved)MET
DABRAFENIBChEMBLPhase 4 (approved)MET

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot