Umbralisib (TGR1202; RP-5264)

Alias:

RP 5264; RP-5264; TGR 1202; Umbralisib; TGR1202; TGR-1202; RP5264;

Cat No.:V0556 Purity: ≥98%

COA Product Data Instructions for use SDS

Umbralisib (formerly TGR-1202; RP-5264; TGR1202; RP5264;Ukoniq) is a novel, highly specific, orally bioavailable and potentPI3Kδinhibitor approved in 2021 by FDA to treat marginal zone lymphoma and follicular lymphoma.

Umbralisib (TGR1202; RP-5264) Chemical Structure CAS No.: 1532533-67-7
Product category: PI3K

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Umbralisib (TGR1202; RP-5264):

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Umbralisib (formerly TGR-1202; RP-5264; TGR1202; RP5264; Ukoniq) is a novel, highly specific, orally bioavailable and potent PI3Kδ inhibitor approved in 2021 by FDA to treat marginal zone lymphoma and follicular lymphoma. With an IC50 and EC50 of 22.2 nM and 24.3 nM, respectively, it inhibits PI3K.

Biological Activity I Assay Protocols (From Reference)

Targets	PI3Kδ (IC50 = 22.2 nM); PI3Kδ (Kd = 6.2 nM); PI3Kγ (Kd = 1400 nM); PI3Kβ (Kd > 10000 nM); PI3Kα (Kd > 10000 nM)
ln Vitro	Umbralisib causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM[3].Umbralisib (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines[4].Umbralisib (15-50 μM) is specifically characterized by structural features suitable for targeting CK1 in lymphoma cells, and it potently inhibits the expression of c-Myc in the DLBCL cell line LY7[4].
ln Vivo	Umbralisib (150 mg/kg, daily p.o.) significantly shrinks the tumors by day 25 in a subcutaneous xenograft model of T-cell acute lymphoblastic leukemia (T-ALL) in NOD/SCID mice using the MOLT-4 cell line[4].
Enzyme Assay	Umbralisib (TGR-1202) is a novelPI3Kδinhibitor, withIC50andEC50of 22.2 nM and 24.3 nM, respectively; Umbralisib (TGR-1202) is also active againstCK1ε, with anEC50value of 6.0 μM.
Cell Assay	Multiple Myeloma resistant (MM-1R) or sensitive (MM-1S) cells are incubated with desired concentrations of RP5264. After 96 hours, a MTT assay is used to measure growth.
Animal Protocol	Female Balb/c mice 12.5, 25, 50 mg/kg oral administration
References	[1]. The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells. Blood Adv. 2020 Jul 14;4(13):3072-3084. [2]. Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 2018 Apr;19(4):486-496. [3]. Inhibition of PI3Kδ kinase by a selective, small molecule inhibitor suppresses B-cell proliferation and leukemic cell growth. [4]. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies. Blood. 2017 Jan 5;129(1):88-99.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C31H24F3N5O3

Molecular Weight

571.5492

Exact Mass

571.18312

Elemental Analysis

C, 65.14; H, 4.23; F, 9.97; N, 12.25; O, 8.40

CAS #

1532533-67-7

Related CAS #

Umbralisib hydrochloride;1532533-78-0;Umbralisib R-enantiomer;1532533-69-9;Umbralisib tosylate;1532533-72-4;Umbralisib sulfate;1532533-75-7

Appearance

Solid powder

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

InChi Key

IUVCFHHAEHNCFT-INIZCTEOSA-N

InChi Code

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

Chemical 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

Synonyms

RP 5264; RP-5264; TGR 1202; Umbralisib; TGR1202; TGR-1202; RP5264;

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)	DMSO: ~100 mg/mL (~175 mM) Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: ~7 mg/mL (~12.2 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2 mg/mL (3.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 2% DMSO+30% PEG 300+2% Tween 80+H2O: 3mg/mL (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ~100 mg/mL (~175 mM)
Water: <1 mg/mL (slightly soluble or insoluble)
Ethanol: ~7 mg/mL (~12.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2 mg/mL (3.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 2: 2% DMSO+30% PEG 300+2% Tween 80+H2O: 3mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7496 mL	8.7481 mL	17.4963 mL
	5 mM	0.3499 mL	1.7496 mL	3.4993 mL
	10 mM	0.1750 mL	0.8748 mL	1.7496 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Status	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03269669	Recruiting	Drug: Prednisone Drug: Umbralisib	Grade 1 Follicular Lymphoma Grade 2 Follicular Lymphoma	National Cancer Institute (NCI)	August 10, 2017	Phase 2
NCT03919175	Active Recruiting	Drug: Umbralisib Drug: Rituximab	Lymphoma Follicular Lymphoma	Massachusetts General Hospital	September 1, 2019	Phase 2
NCT04783415	Active Recruiting	Drug: Acalabrutinib Drug: Umbralisib	Mantle Cell Lymphoma	City of Hope Medical Center	March 26, 2021	Phase 2
NCT04624633	Active Recruiting	Drug: Acalabrutinib Drug: Umbralisib	Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Jennifer R. Brown, MD, PhD	March 26, 2021	Phase 2
NCT03671590	Active Recruiting	Drug: TG-1701 Drug: Umbralisib	Non Hodgkin Lymphoma	TG Therapeutics, Inc.	September 10, 2018	Phase 1

Biological Data

TGR-1202 and carfilzomib synergistically inhibit survival of lymphoma and leukemia cell lines and primary cells.Blood.2017 Jan 5;129(1):88-99.
TGR-1202 and carfilzomib synergistically inhibits translation of c-Myc in lymphoma and myeloma cell lines.Blood.2017 Jan 5;129(1):88-99.
TGR-1202 and carfilzomib inhibits c-Myc–dependent gene transcription.Blood.2017 Jan 5;129(1):88-99.