RP 5264; RP-5264; TGR 1202; Umbralisib; TGR1202; TGR-1202; RP5264;
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
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.
Targets |
PI3Kδ (IC50 = 22.2 nM); PI3Kδ (Kd = 6.2 nM); PI3Kγ (Kd = 1400 nM); PI3Kβ (Kd > 10000 nM); PI3Kα (Kd > 10000 nM)
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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].
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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].
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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.
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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.
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Animal Protocol |
Female Balb/c mice
12.5, 25, 50 mg/kg oral administration |
References |
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Molecular Formula |
C31H24F3N5O3
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Molecular Weight |
571.5492
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Exact Mass |
571.18312
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Elemental Analysis |
C, 65.14; H, 4.23; F, 9.97; N, 12.25; O, 8.40
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CAS # |
1532533-67-7
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Related CAS # |
Umbralisib hydrochloride;1532533-78-0;Umbralisib R-enantiomer;1532533-69-9;Umbralisib tosylate;1532533-72-4;Umbralisib sulfate;1532533-75-7
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Appearance |
Solid powder
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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
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InChi Key |
IUVCFHHAEHNCFT-INIZCTEOSA-N
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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
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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
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~100 mg/mL (~175 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: ~7 mg/mL (~12.2 mM) |
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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.
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.
(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.
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 |
TGR-1202 and carfilzomib synergistically inhibit survival of lymphoma and leukemia cell lines and primary cells.Blood.2017 Jan 5;129(1):88-99. td> |
TGR-1202 and carfilzomib synergistically inhibits translation of c-Myc in lymphoma and myeloma cell lines.Blood.2017 Jan 5;129(1):88-99. td> |
TGR-1202 and carfilzomib inhibits c-Myc–dependent gene transcription.Blood.2017 Jan 5;129(1):88-99. td> |