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Umbralisib

drug
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Also known as RP-5264RP5264Tgr 1202TGR-1202 FREE BASETGR-1202 baseUS9150579B1TGR-1202TG

Summary

Umbralisib (CHEMBL3948730) is an approved small molecule (ATC L01EX25) targeting CSNK1E and PIK3CD; indicated across 9 conditions including neoplasm and b-cell chronic lymphocytic leukemia.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EX25
  • Targets: 2 (CSNK1E, PIK3CD)
  • Indications: 9 conditions
  • Clinical trials: 21
  • Chemistry: 571.5 Da · C31H24F3N5O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3948730
NameUmbralisib
TypeSmall molecule
Max phase4
FDA approvedno
PubChem CID72950888
ATCL01EX25
Molecular formulaC31H24F3N5O3
Molecular weight571.5
InChIKeyIUVCFHHAEHNCFT-INIZCTEOSA-N

SMILES: C[C@@H](C1=C(C(=O)C2=C(O1)C=CC(=C2)F)C3=CC(=CC=C3)F)N4C5=NC=NC(=C5C(=N4)C6=CC(=C(C=C6)OC(C)C)F)N

IUPAC name: 2-[(1S)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one

Also known as: RP-5264, RP5264, Tgr 1202, TGR-1202 FREE BASE, TGR-1202 base, Umbralisib, US9150579, B1, UMBRALISIB, umbralisib, TGR-1202, TG

Parent form; salt/anhydrous children: CHEMBL3989869

Patent coverage: 1,033 distinct patent families (2,833 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 2,662 (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
CSNK1Ecasein kinase 1 epsilonInhibition5.22P49674
PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit deltaInhibition7.866%O00329

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: PI3-kinase p110-delta/p85-alpha, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Casein kinase I isoform epsilon.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PIK3CD8.21IC506.2nMCHEMBL_ACT_18952538
PIK3CD7.85IC5014nMCHEMBL_ACT_19036914
PIK3CD7.85IC5014nMCHEMBL_ACT_24954280
PIK3CD7.66IC5022nMCHEMBL_ACT_25556642
PIK3CD7.65IC5022.33nMCHEMBL_ACT_17711156
PIK3CD7.65EC5022.2nMCHEMBL_ACT_26330942
PIK3CD7.65IC5022.2nMCHEMBL_ACT_29055480
PIK3CD7.32IC5048.4nMCHEMBL_ACT_22775092
PIK3CD6.5IC50316nMCHEMBL_ACT_25634113
PIK3CG5.85IC501400nMCHEMBL_ACT_18952546
CSNK1E5.22EC506000nMCHEMBL_ACT_26331078
CSNK1E5.22IC506000nMCHEMBL_ACT_29055489

Target pathways

Aggregated over 2 target gene(s): CSNK1E, PIK3CD.

Top Reactome pathways

42 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling1PIK3CD
Signal Transduction1CSNK1E
Cell Cycle1CSNK1E
Synthesis of PIPs at the plasma membrane1PIK3CD
Organelle biogenesis and maintenance1CSNK1E
Signaling by WNT1CSNK1E
TCF dependent signaling in response to WNT1CSNK1E
WNT mediated activation of DVL1CSNK1E
Constitutive Signaling by Aberrant PI3K in Cancer1PIK3CD
Regulation of PLK1 Activity at G2/M Transition1CSNK1E
Loss of Nlp from mitotic centrosomes1CSNK1E
Recruitment of mitotic centrosome proteins and complexes1CSNK1E
Loss of proteins required for interphase microtubule organization from the centrosome1CSNK1E
Centrosome maturation1CSNK1E
Recruitment of NuMA to mitotic centrosomes1CSNK1E
CD28 dependent PI3K/Akt signaling1PIK3CD
R-HSA-4002531CSNK1E
Mitotic G2-G2/M phases1CSNK1E
Interleukin-3, Interleukin-5 and GM-CSF signaling1PIK3CD
Cilium Assembly1CSNK1E
Anchoring of the basal body to the plasma membrane1CSNK1E
Major pathway of rRNA processing in the nucleolus and cytosol1CSNK1E
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling1PIK3CD
Mitotic Prometaphase1CSNK1E
M Phase1CSNK1E
G2/M Transition1CSNK1E
Cell Cycle, Mitotic1CSNK1E
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A1CSNK1E
rRNA processing1CSNK1E
RET signaling1PIK3CD
AURKA Activation by TPX21CSNK1E
rRNA processing in the nucleus and cytosol1CSNK1E
Metabolism of RNA1CSNK1E
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)1PIK3CD
Interleukin receptor SHC signaling1PIK3CD
Regulation of signaling by CBL1PIK3CD
Signaling by CSF1 (M-CSF) in myeloid cells1PIK3CD
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers1PIK3CD
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells1PIK3CD
Co-stimulation by ICOS1PIK3CD
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex1CSNK1E
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex1CSNK1E

Dominant GO biological processes

GO termTargets
protein phosphorylation2
signal transduction2
DNA repair1
endocytosis1
intracellular protein localization1
negative regulation of Wnt signaling pathway1
positive regulation of proteasomal ubiquitin-dependent protein catabolic process1
regulation of protein localization1
circadian regulation of gene expression1
non-canonical Wnt signaling pathway1
regulation of circadian rhythm1
circadian behavior1
negative regulation of small GTPase mediated signal transduction1
canonical Wnt signaling pathway1
positive regulation of canonical Wnt signaling pathway1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

IndicationPhaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616

8 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)PhaseMONDOEFO
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
Hodgkins lymphoma2MONDO:0004952EFO:0000183
Waldenstrom macroglobulinemia2MONDO:0100280EFO:0009441
mantle cell lymphoma2MONDO:0018876EFO:1001469
follicular lymphoma2MONDO:0018906MONDO:0018906
diffuse large B-cell lymphoma2MONDO:0018905EFO:0000403
neoplasm of mature B-cells2MONDO:0004949EFO:0000096
non-Hodgkin lymphoma2MONDO:0018908EFO:0005952

Clinical trials

Total trials: 21.

Phase distribution

PhaseTrials
PHASE213
PHASE1/PHASE23
PHASE13
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02793583PHASE2/PHASE3TERMINATEDStudy to Assess the Efficacy and Safety of Ublituximab + Umbralisib With or Without Bendamustine and Umbralisib Alone in Patients With Previously Treated Non-Hodgkins Lymphoma
NCT03801525PHASE2/PHASE3TERMINATEDStudy to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)
NCT03269669PHASE2ACTIVE_NOT_RECRUITINGObinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma
NCT04624633PHASE2ACTIVE_NOT_RECRUITINGAcalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL
NCT04783415PHASE2ACTIVE_NOT_RECRUITINGAcalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma
NCT02656303PHASE2TERMINATEDA Study to Evaluate the Safety and Efficacy of Ublituximab in Combination With Umbralisib for Participants Previously Enrolled in Protocol UTX-TGR-304
NCT02742090PHASE2TERMINATEDEvaluate the Efficacy and Safety of TGR-1202 in Participants With Chronic Lymphocytic Leukemia Who Are Intolerant to Prior Therapy
NCT03364231PHASE2COMPLETEDStudy to Assess the Efficacy and Safety of Umbralisib in Participants With Non-Follicular Indolent Non-Hodgkin’s Lymphoma
NCT03379051PHASE1/PHASE2TERMINATEDPhase I/II Study of Venetoclax or Lenalidomide in Combination With Ublituximab and Umbralisib in Subjects With Relapsed or Refractory CLL/SLL and NHL
NCT03776864PHASE2TERMINATEDUmbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
NCT03828448PHASE2TERMINATEDStudy to Assess Umbralisib Plus Ublituximab in Participants With Treatment Naïve Follicular Lymphoma
NCT03919175PHASE2TERMINATEDUmbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma
NCT04016805PHASE2TERMINATEDStudy to Assess the Efficacy and Safety of Ublituximab and Umbralisib in Participants With Chronic Lymphocytic Leukemia (CLL) Currently Treated With Ibrutinib, Acalabrutinib or Venetoclax
NCT04149821PHASE2TERMINATEDUmbralisib Plus Ublituximab (U2) in Progressive CLL After Novel Therapy
NCT04163718PHASE2TERMINATEDTGR-1202 (Umbralisib) in Treatment Naïve Patients With Chronic Lymphocytic Leukemia (CLL)
NCT04508647PHASE2COMPLETEDUblituximab Followed by Response-driven Addition of Umbralisib for Treatment-naive Follicular or Marginal Zone Lymphoma
NCT04692155PHASE1/PHASE2TERMINATEDClinical Trial of Ublituximab and Umbralisib With CHOP (U2-CHOP) Followed by U2 Maintenance (U2-CHOP-U2) in Previously Untreated Mantle Cell Lymphoma (MCL)
NCT05152459PHASE1/PHASE2WITHDRAWNTazemetostat in Combination With Umbralisib and Ublituximab for the Treatment Relapsed or Refractory Follicular Lymphoma
NCT02535286PHASE1COMPLETEDStudy of Immunotherapy in Combination With Ublituximab and Umbralisib in Patients With Relapsed-refractory CLL or Richter’s Transformation
NCT03671590PHASE1TERMINATEDStudy of TG-1701, an Irreversible Bruton’s Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies
NCT04635683PHASE1WITHDRAWNLenalidomide, Umbralisib, and Ublituximab for the Treatment of Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

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.

87 molecules share ≥1 primary target. Top 87 by shared-target count:

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)CSNK1E, PIK3CD
GEFITINIBChEMBL + PubChemPhase 4 (approved)CSNK1E, PIK3CD
IdelalisibChEMBL + PubChemPhase 4 (approved)CSNK1E, PIK3CD
DASATINIBChEMBLPhase 4 (approved)CSNK1E, PIK3CD
SUNITINIBChEMBLPhase 4 (approved)CSNK1E, PIK3CD
BI-2536ChEMBLPhase 2CSNK1E, PIK3CD
PICTILISIBChEMBLPhase 2CSNK1E, PIK3CD
TG100-115ChEMBLPhase 2CSNK1E, PIK3CD
CrizotinibPubChemApprovedCSNK1E, PIK3CD
PazopanibPubChemApprovedCSNK1E, PIK3CD
SelumetinibPubChemApprovedCSNK1E, PIK3CD
INAVOLISIBChEMBL + PubChemPhase 4 (approved)PIK3CD
ALPELISIBChEMBLPhase 4 (approved)PIK3CD
BOSUTINIBChEMBLPhase 4 (approved)CSNK1E
CAFFEINEChEMBLPhase 4 (approved)PIK3CD
COPANLISIBChEMBLPhase 4 (approved)PIK3CD
DUVELISIBChEMBLPhase 4 (approved)PIK3CD
ERLOTINIBChEMBLPhase 4 (approved)CSNK1E
LENIOLISIBChEMBLPhase 4 (approved)PIK3CD
NERATINIBChEMBLPhase 4 (approved)CSNK1E
NINTEDANIBChEMBLPhase 4 (approved)CSNK1E
THEOPHYLLINEChEMBLPhase 4 (approved)PIK3CD
VANDETANIBChEMBLPhase 4 (approved)CSNK1E
BUPARLISIBChEMBLPhase 3PIK3CD
CANERTINIBChEMBLPhase 3CSNK1E
CEDIRANIBChEMBLPhase 3CSNK1E
DACTOLISIBChEMBLPhase 3PIK3CD
EPIGALOCATECHIN GALLATEChEMBLPhase 3CSNK1E
GEDATOLISIBChEMBLPhase 3PIK3CD
LESTAURTINIBChEMBLPhase 3PIK3CD
PARSACLISIBChEMBLPhase 3PIK3CD
POVORCITINIBChEMBLPhase 3PIK3CD
TASELISIBChEMBLPhase 3PIK3CD
TESEVATINIBChEMBLPhase 3CSNK1E
ACALISIBChEMBLPhase 2PIK3CD
AMDIZALISIBChEMBLPhase 2PIK3CD
AMG-319ChEMBLPhase 2PIK3CD
APITOLISIBChEMBLPhase 2PIK3CD
AZD-6482ChEMBLPhase 2PIK3CD
AZD-8154ChEMBLPhase 2PIK3CD
BGT-226 FREE BASEChEMBLPhase 2PIK3CD
BIMIRALISIBChEMBLPhase 2PIK3CD
BMS-690514ChEMBLPhase 2CSNK1E
CC-401ChEMBLPhase 2CSNK1E
DEZAPELISIBChEMBLPhase 2PIK3CD
EGANELISIBChEMBLPhase 2PIK3CD
FIMEPINOSTATChEMBLPhase 2PIK3CD
FORETINIBChEMBLPhase 2CSNK1E
GALUNISERTIBChEMBLPhase 2CSNK1E
GSK-2636771ChEMBLPhase 2PIK3CD
IZORLISIBChEMBLPhase 2PIK3CD
LINPERLISIBChEMBLPhase 2PIK3CD
MILCICLIBChEMBLPhase 2CSNK1E
NARAZACICLIBChEMBLPhase 2PIK3CD
NEMIRALISIBChEMBLPhase 2PIK3CD
OMIPALISIBChEMBLPhase 2PIK3CD
ONATASERTIBChEMBLPhase 2PIK3CD
OSI-632ChEMBLPhase 2CSNK1E
PAMAPIMODChEMBLPhase 2CSNK1E
PAXALISIBChEMBLPhase 2PIK3CD
PELITINIBChEMBLPhase 2CSNK1E
PF-04691502ChEMBLPhase 2PIK3CD
PILARALISIBChEMBLPhase 2PIK3CD
QUISINOSTATChEMBLPhase 2PIK3CD
R-406ChEMBLPhase 2PIK3CD
RISOVALISIBChEMBLPhase 2PIK3CD
ROGINOLISIBChEMBLPhase 2PIK3CD
SAMOTOLISIBChEMBLPhase 2PIK3CD
SAPANISERTIBChEMBLPhase 2PIK3CD
SELETALISIBChEMBLPhase 2PIK3CD
SELICICLIBChEMBLPhase 2CSNK1E
SERABELISIBChEMBLPhase 2PIK3CD
SILMITASERTIBChEMBLPhase 2CSNK1E
SONOLISIBChEMBLPhase 2PIK3CD
SU-014813ChEMBLPhase 2CSNK1E
TAK-715ChEMBLPhase 2CSNK1E
TENALISIBChEMBLPhase 2PIK3CD
VISTUSERTIBChEMBLPhase 2PIK3CD
VOXTALISIBChEMBLPhase 2PIK3CD
ZSTK-474ChEMBLPhase 2PIK3CD
BinimetinibPubChemApprovedCSNK1E
CobimetinibPubChemApprovedCSNK1E
dacomitinibPubChemApprovedCSNK1E
FedratinibPubChemApprovedCSNK1E
FostamatinibPubChemApprovedCSNK1E
regorafenibPubChemApprovedCSNK1E
TrametinibPubChemApprovedCSNK1E

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
v1.1.4
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