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Pirtobrutinib

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Also known as JaypircaLoxo-305LY-3527727LY3527727RXC-005

Summary

Pirtobrutinib (CHEMBL4650485) is an approved small-molecule EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor (ATC L01EL05) targeting BTK; indicated across 8 conditions including mantle cell lymphoma and neoplasm.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EL05
  • Targets: 1 (BTK)
  • Indications: 8 conditions
  • Clinical trials: 65
  • Chemistry: 479.4 Da · C22H21F4N5O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4650485
NamePirtobrutinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID129269915
ChEBICHEBI:229212
ATCL01EL05
Molecular formulaC22H21F4N5O3
Molecular weight479.4
InChIKeyFWZAWAUZXYCBKZ-NSHDSACASA-N

SMILES: C[C@@H](C(F)(F)F)N1C(=C(C(=N1)C2=CC=C(C=C2)CNC(=O)C3=C(C=CC(=C3)F)OC)C(=O)N)N

IUPAC name: 5-amino-3-[4-[[(5-fluoro-2-methoxybenzoyl)amino]methyl]phenyl]-1-[(2S)-1,1,1-trifluoropropan-2-yl]pyrazole-4-carboxamide

ChEBI definition: A secondary carboxamide resulting from the formal condensation of the carboxy group of 5-fluoro-2-methoxybenzoic acid with the amino group of 5-amino-3-[4-(aminomethyl)phenyl]-1-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-pyrazole-4-carboxamide. It is a BTK inhibitor used for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Pharmacological roles (ChEBI): EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, antineoplastic agent, apoptosis inducer.

Also known as: Jaypirca, Loxo-305, LOXO-305, LY-3527727, LY3527727, Pirtobrutinib, RXC-005, PIRTOBRUTINIB, pirtobrutinib

Patent coverage: 216 distinct patent families (427 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 401 (94%) 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
BTKBruton tyrosine kinaseInhibition8.060.7%Q06187

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

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 3 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
BTK8.43IC503.68nMCHEMBL_ACT_29055466
BTK8.07IC508.45nMCHEMBL_ACT_29055467
BTK7.93IC5011.73nMCHEMBL_ACT_29055469

Target pathways

Aggregated over 1 target gene(s): BTK.

Top Reactome pathways

45 total, by targets touching each:

PathwayTargetsGenes
ER-Phagosome pathway1BTK
Antigen processing-Cross presentation1BTK
Adaptive Immune System1BTK
Signal Transduction1BTK
Disease1BTK
Toll Like Receptor 4 (TLR4) Cascade1BTK
MyD88:MAL(TIRAP) cascade initiated on plasma membrane1BTK
Toll Like Receptor TLR1:TLR2 Cascade1BTK
Toll Like Receptor TLR6:TLR2 Cascade1BTK
Innate Immune System1BTK
Immune System1BTK
Toll-like Receptor Cascades1BTK
Toll Like Receptor 2 (TLR2) Cascade1BTK
Signaling by Rho GTPases1BTK
RHO GTPase Effectors1BTK
Fcgamma receptor (FCGR) dependent phagocytosis1BTK
Regulation of actin dynamics for phagocytic cup formation1BTK
DAP12 interactions1BTK
DAP12 signaling1BTK
Fc epsilon receptor (FCERI) signaling1BTK
FCERI mediated Ca+2 mobilization1BTK
Signaling by GPCR1BTK
GPCR downstream signalling1BTK
G-protein beta:gamma signalling1BTK
G alpha (q) signalling events1BTK
G alpha (12/13) signalling events1BTK
Diseases of Immune System1BTK
Diseases associated with the TLR signaling cascade1BTK
MyD88 deficiency (TLR2/4)1BTK
IRAK4 deficiency (TLR2/4)1BTK

Dominant GO biological processes

GO termTargets
neutrophil homeostasis1
positive regulation of type III hypersensitivity1
positive regulation of type I hypersensitivity1
adaptive immune response1
B cell affinity maturation1
histamine secretion by mast cell1
positive regulation of immunoglobulin production1
regulation of B cell cytokine production1
MyD88-dependent toll-like receptor signaling pathway1
regulation of B cell apoptotic process1
mesoderm development1
peptidyl-tyrosine phosphorylation1
calcium-mediated signaling1
proteoglycan catabolic process1
negative regulation of B cell proliferation1

Indications & clinical

Indications

8 indications (2 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
mantle cell lymphoma4MONDO:0018876EFO:1001469
neoplasm4MONDO:0005070EFO:0000616
B-cell chronic lymphocytic leukemia3MONDO:0004948EFO:0000095
leukemia2MONDO:0005059EFO:0000565
Waldenstrom macroglobulinemia2MONDO:0100280EFO:0009441
marginal zone lymphoma2MONDO:0017604EFO:1000630
multiple sclerosis2MONDO:0005301MONDO:0005301
kidney failure1MONDO:0001106HP:0000083

Clinical trials

Total trials: 65.

Phase distribution

PhaseTrials
PHASE229
PHASE116
PHASE39
PHASE1/PHASE25
PHASE43
Not specified2
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06876649PHASE4RECRUITINGA Master Protocol to Evaluate the Long-Term Safety of (LY3527727) Pirtobrutinib
NCT06876662PHASE4RECRUITINGA Study of (LY3527727) Pirtobrutinib in Participants With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma
NCT07218341PHASE4RECRUITINGA Study of Pirtobrutinib (LY3527727) in Participants With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT04662255PHASE3ACTIVE_NOT_RECRUITINGStudy of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
NCT04666038PHASE3ACTIVE_NOT_RECRUITINGStudy of LOXO-305 (Pirtobrutinib) Versus Investigator’s Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT04965493PHASE3ACTIVE_NOT_RECRUITINGA Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
NCT05023980PHASE3ACTIVE_NOT_RECRUITINGA Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT05254743PHASE3RECRUITINGA Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT06973187PHASE3RECRUITINGA Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT07220187PHASE3NOT_YET_RECRUITINGAdding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial
NCT07342478PHASE3RECRUITINGROCKET-CLL Global Phase 3 Study: Rocbrutinib vs Pirtobrutinib in cBTKi-Pretreated R/R CLL/SLL
NCT07516093PHASE3NOT_YET_RECRUITINGStudy of NX-5948 Versus Pirtobrutinib in R/R CLL/SLL
NCT04623541PHASE1/PHASE2ACTIVE_NOT_RECRUITINGSafety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter’s Syndrome
NCT05529069PHASE2RECRUITINGPhase II Study of Pirtobrutinib With Venetoclax In Relapsed-Refractory MCL (Mantle Cell Lymphoma) Patients
NCT05536349PHASE2RECRUITINGTime-limited Triplet Combination of Pirtobrutinib, Venetoclax, and Obinutuzumab for Patients With Treatment-naïve Chronic Lymphocytic Leukemia (CLL) or Richter Transformation (RT)
NCT05677919PHASE2ACTIVE_NOT_RECRUITINGPirtobrutinib and Venetoclax With MRD Detection for Previously Untreated Chronic Lymphocytic Leukemia
NCT05734495PHASE2ACTIVE_NOT_RECRUITINGPirtobrutinib and Venetoclax in Waldenström Macroglobulinemia
NCT05833763PHASE2RECRUITINGA Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure.
NCT06043674PHASE2RECRUITINGPhase 2 Study of Glofitamab Monotherapy & With Polatuzumab Vedotin, Pirtobrutinib, or Atezolizumab in Richter’s Transformation
NCT06252675PHASE2RECRUITINGGlofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma
NCT06263491PHASE2RECRUITINGPhase II Study of Pirtobrutinib, Rituximab (PR) in Previously Untreated Low and Intermediate Risk MCL (Mantle Cell Lymphoma) Patients
NCT06333262PHASE2RECRUITINGFixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia
NCT06390956PHASE2RECRUITINGPirtobrutinib in Combination With Rituximab in Adults With Untreated Marginal Zone Lymphoma (PIONEER-MZL)
NCT06466122PHASE2RECRUITINGPirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi
NCT06522386PHASE2ACTIVE_NOT_RECRUITINGGATE1: A Multicenter Phase II Study of Pirtobrutinib, Rituximab and Venetoclax Combination Therapy for Patients With Previously Untreated Mantle Cell Lymphoma
NCT06553872PHASE2RECRUITINGPhase 2 Open Label Randomized Study of Pirtobrutinib and Brexucabtagene Autoleucel in R/R MCL
NCT06588478PHASE2RECRUITINGA Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT06721013PHASE1/PHASE2RECRUITINGA Study of Pirtobrutinib in Participants With Immune Thrombocytopenia
NCT06812715PHASE2RECRUITINGClonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib
NCT06948786PHASE2RECRUITINGPirtobrutinib and Mosunetuzumab for the Treatment of Relapsed/Refractory Grades 1-3A Follicular Lymphoma, PROMOTE-FL Trial
NCT06967610PHASE2RECRUITINGPhase II Study of Combined Pirtobrutinib, Venetoclax and Obinutuzumab (PVO) Time-limited Treatment for Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).
NCT07052695PHASE1/PHASE2RECRUITINGMosunetuzumab for CLL MRD Clearance
NCT07122609PHASE2NOT_YET_RECRUITINGPirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma
NCT07162181PHASE2ACTIVE_NOT_RECRUITINGLong-Term Safety of Pirtobrutinib in Participants With Previously Treated Types of Blood Cancers
NCT07207785PHASE2NOT_YET_RECRUITINGPirtobrUtinib as Frontline Therapy for Elderly Unfit/Frail Patient With MAntle Cell Lymphoma
NCT07231952PHASE2RECRUITINGA Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström’s Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
NCT07255963PHASE2RECRUITINGPirtobrutinib, Lisaftoclax, and Rituximab in the Treatment of R/R DLBCL
NCT07285590PHASE2RECRUITINGClinical Trial to Evaluate the Efficacy and Safety of Pirtobrutinib With Rituximab in Patients With Mantle Cell Lymphoma
NCT07350850PHASE2RECRUITINGA Multicenter Two-Cohort Study of Methotrexate, Rituximab, Sintilimab and Pirtobrutinib for Treatment-Naive PCNSL vs. Real-World Investigator-Selected Treatment (Observational Cohort)
NCT07416890PHASE2RECRUITINGThiotepa in Combination With Pirtobrutinib (a BTK Inhibitor) and Sintilimab (a PD-1 Inhibitor) for Frail or Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma

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.

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.

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

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)BTK
RITLECITINIBChEMBL + PubChemPhase 4 (approved)BTK
ACALABRUTINIBChEMBLPhase 4 (approved)BTK
BOSUTINIBChEMBLPhase 4 (approved)BTK
BRIGATINIBChEMBLPhase 4 (approved)BTK
CERITINIBChEMBLPhase 4 (approved)BTK
DASATINIBChEMBLPhase 4 (approved)BTK
ENTRECTINIBChEMBLPhase 4 (approved)BTK
FEDRATINIBChEMBLPhase 4 (approved)BTK
FUTIBATINIBChEMBLPhase 4 (approved)BTK
IBRUTINIBChEMBLPhase 4 (approved)BTK
MITOXANTRONEChEMBLPhase 4 (approved)BTK
NERATINIBChEMBLPhase 4 (approved)BTK
NINTEDANIBChEMBLPhase 4 (approved)BTK
OLMUTINIBChEMBLPhase 4 (approved)BTK
OSIMERTINIBChEMBLPhase 4 (approved)BTK
PONATINIBChEMBLPhase 4 (approved)BTK
SUNITINIBChEMBLPhase 4 (approved)BTK
TIRABRUTINIBChEMBLPhase 4 (approved)BTK
VANDETANIBChEMBLPhase 4 (approved)BTK
ZANUBRUTINIBChEMBLPhase 4 (approved)BTK
ABIVERTINIBChEMBLPhase 3BTK
ALISERTIBChEMBLPhase 3BTK
CANERTINIBChEMBLPhase 3BTK
CEDIRANIBChEMBLPhase 3BTK
DOVITINIBChEMBLPhase 3BTK
ENTOSPLETINIBChEMBLPhase 3BTK
EVOBRUTINIBChEMBLPhase 3BTK
FENEBRUTINIBChEMBLPhase 3BTK
LESTAURTINIBChEMBLPhase 3BTK
NEMTABRUTINIBChEMBLPhase 3BTK
ORELABRUTINIBChEMBLPhase 3BTK
POZIOTINIBChEMBLPhase 3BTK
PYROTINIBChEMBLPhase 3BTK
REMIBRUTINIBChEMBLPhase 3BTK
RILZABRUTINIBChEMBLPhase 3BTK
ROCILETINIBChEMBLPhase 3BTK
SARACATINIBChEMBLPhase 3BTK
TESEVATINIBChEMBLPhase 3BTK
TOLEBRUTINIBChEMBLPhase 3BTK
APITOLISIBChEMBLPhase 2BTK
AT-9283ChEMBLPhase 2BTK
ATUZABRUTINIBChEMBLPhase 2BTK
BIIB-091ChEMBLPhase 2BTK
BMS-754807ChEMBLPhase 2BTK
BMS-919373ChEMBLPhase 2BTK
BMS-986142ChEMBLPhase 2BTK
BRANEBRUTINIBChEMBLPhase 2BTK
CENISERTIBChEMBLPhase 2BTK
CEP-11981ChEMBLPhase 2BTK
DANUSERTIBChEMBLPhase 2BTK
DEFOSBARASERTIBChEMBLPhase 2BTK
EDRALBRUTINIBChEMBLPhase 2BTK
ELSUBRUTINIBChEMBLPhase 2BTK
FORETINIBChEMBLPhase 2BTK
ILORASERTIBChEMBLPhase 2BTK
MILREBRUTINIBChEMBLPhase 2BTK
PELITINIBChEMBLPhase 2BTK
POSELTINIBChEMBLPhase 2BTK
R-406ChEMBLPhase 2BTK

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
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot