UMBRALISIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H24F3N5O3
Molecular Weight	571.5492
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)OC1=CC=C(C=C1F)C2=NN([C@@H](C)C3=C(C4=CC(F)=CC=C4)C(=O)C5=C(O3)C=CC(F)=C5)C6=C2C(N)=NC=N6

InChI

InChIKey=IUVCFHHAEHNCFT-INIZCTEOSA-N

InChI=1S/C31H24F3N5O3/c1-15(2)41-24-9-7-18(12-22(24)34)27-26-30(35)36-14-37-31(26)39(38-27)16(3)29-25(17-5-4-6-19(32)11-17)28(40)21-13-20(33)8-10-23(21)42-29/h4-16H,1-3H3,(H2,35,36,37)/t16-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.tgtherapeutics.com/pipeline/TGR-1202.cfm | https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C104413

Umbralisib (TGR-1202) is an orally available PI3K delta inhibitor, targeting the delta isoform with nanomolar potency and several fold selectivity over the alpha, beta, and gamma isoforms of PI3K. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-cell lymphocytes. Inhibition of PI3K delta signaling with umbralisib has demonstrated robust activity in numerous pre-clinical models and primary cells from patients with hematologic malignancies. Umbralisib is currently in Phase 3 clinical development in combination with Ublituximab for patients with hematologic malignancies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27784673	Inhibitor 8297	22.2 nM [EC50]
Casein kinase I isoform epsilon 2 Target ID: P49674 Gene ID: 102800317\|\|\|1454 Gene Symbol: CSNK1E Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27784673	Inhibitor 8297
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 9 Target ID: O00329 Gene ID: 5293.0 Gene Symbol: PIK3CD Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/29475723	Inhibitor 8297	6.2 nM [Kd]
Casein kinase I isoform epsilon 2 Target ID: P49674 Gene ID: 102800317\|\|\|1454 Gene Symbol: CSNK1E Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/29475723	Inhibitor 8297	180.0 nM [Kd]

PubMed

Title	Date	PubMed
Can umbralisib bring PI3Kδ out of the shadows?	2018 Apr	29475725
Umbralisib Inhibits PI3Kδ with Less Toxicity Than Previous Inhibitors.	2018 Apr	29500299
Umbralisib: Treatment for a Rare Lymphoma?	2019 Jun	30936084

Patents

Sample Use Guides

In Vivo Use Guide

relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: umbralisib orally once daily (400 mg, 600 mg, or 800 mg) and ibrutinib orally once daily (420 mg for chronic lymphocytic leukaemia or 560 mg for mantle cell lymphoma) until disease progression or unacceptable toxicity. Umbralisib plus ibrutinib is well tolerated and active in relapsed or refractory chronic lymphocytic leukaemia and mantle cell lymphoma, with a recommended phase 2 dose of umbralisib 800 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Umbralisib (TGR-1202), a novel, next generation PI3Kδ inhibitor, inhibits PI3Kδ activity in enzyme and cell based assays with IC50 and EC50 values of 22.2 & 24.3 nM, respectively.

Name

Type

Language

UMBRALISIB

Official Name

English

RP-5264

Code

English

4H-1-BENZOPYRAN-4-ONE, 2-((1S)-1-(4-AMINO-3-(3-FLUORO-4-(1-METHYLETHOXY)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)ETHYL)-6-FLUORO-3-(3-FLUOROPHENYL)-

Systematic Name

English

Umbralisib [WHO-DD]

Common Name

English

2-((1S)-1-(4-AMINO-3-(3-FLUORO-4-(1-METHYLETHOXY)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)ETHYL)-6-FLUORO-3-(3-FLUOROPHENYL)-4H-1-BENZOPYRAN-4-ONE

Systematic Name

English

TGR-1202

Code

English

UMBRALISIB [USAN]

Common Name

English

umbralisib [INN]

Common Name

English

RP5264

Code

English

TGR-1202 FREE BASE

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

687519