umbralisib   Click here for help

GtoPdb Ligand ID: 8916

Synonyms: example A1 [US2014011819] | RP-5264 | RP5264 | TGR-1202 | TGR1202 | Ukoniq®
Approved drug Immunopharmacology Ligand
umbralisib is an approved drug (FDA (2021))
Compound class: Synthetic organic
Comment: Umbralisib (TGR-1202; RP5264,) is an orally available, selective inhibitor of the δ isoform of phosphoinositide 3-kinase (PI3K) [1,3,5], that was developed by TG Therapeutics for the treatment of several B cell malignancies. It also inhibits casein kinase-1ε [2]. For clinical application umbralisib is formulated as the tosylate salt.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

umbralisib is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 109.06
Molecular weight 571.18
XLogP 8.24
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES CC(Oc1ccc(cc1F)c1nn(c2c1c(N)ncn2)C(c1oc2ccc(cc2c(=O)c1c1cccc(c1)F)F)C)C
Isomeric SMILES CC(Oc1ccc(cc1F)c1nn(c2c1c(N)ncn2)[C@H](c1oc2ccc(cc2c(=O)c1c1cccc(c1)F)F)C)C
InChI 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
InChI Key IUVCFHHAEHNCFT-INIZCTEOSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Umbralisib was evaluated in a number of clinical trials in patients with various hematological malignancies and successfully progressed to Phase 3 in combination with ublituximab (and in comparison to obinutuzumab + chlorambucil) in CLL (NCT02612311). Phase 1 study results indicated that umbralisib was well tolerated and showed preliminary signs efficacy in patients with relapsed/refractory haematological malignancies, and had an improved safety profile in comparison to other PI3Kδ inhibitors [2].
In January 2019, TG Therapeutics announced that the FDA had granted Breakthrough Therapy Designation for umbralisib for the treatment of adult patients with marginal zone lymphoma (MZL, an indolent B-cell non-Hodgkin lymphoma) who have received at least one prior anti-CD20 therapy [4], based on interim data from the MZL cohort receiving umbralisib monotherapy in the UNITY-NHL trial NCT02793583.
Accelerated FDA approval was granted in February 2021, for the MZL indication and for relapsed/refractory follicular lymphoma (FL) in patients who have been treated with >3 systemic therapy regimens.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02612311 Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Patients With Untreated and Previously Treated Chronic Lymphocytic Leukemia Phase 3 Interventional TG Therapeutics, Inc.
NCT02793583 Study to Assess the Efficacy and Safety of Ublituximab + TGR-1202 With or Without Bendamustine and TGR-1202 Alone in Patients With Previously Treated Non-Hodgkins Lymphoma Phase 2/Phase 3 Interventional TG Therapeutics, Inc.