| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PI3Kδ (IC50 = 22.2 nM); PI3Kδ (Kd = 6.2 nM); PI3Kγ (Kd = 1400 nM); PI3Kβ (Kd = >10000 nM); PI3Kα (Kd >10000 nM)
Umbralisib hydrochloride targets PI3Kδ with an IC₅₀ of 22.2 nM and CK1ε with an EC₅₀ of 6.0 μM. It exhibits Kd values of 6.2 nM for PI3Kδ, 1400 nM for PI3Kγ, and >10,000 nM for PI3Kα and PI3Kβ. By inhibiting PI3Kδ, the compound blocks the PI3K/AKT signaling pathway, which is critical for B-cell survival, proliferation, and migration. Inhibition of CK1ε further contributes to its anticancer activity. |
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| ln Vitro |
Umbralisib hydrochloride causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM[3].
Umbralisib hydrochloride (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines[4].
Umbralisib hydrochloride (15-50 μM) potently inhibits the expression of c-Myc in the DLBCL cell line LY7 and is structurally distinct enough to target CK1 in lymphoma cells[4].
In vitro, Umbralisib hydrochloride causes half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM. It inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines at 10 nM-100 μM. At 15-50 μM, the compound potently inhibits the expression of c-Myc in DLBCL cell lines and targets CK1 in lymphoma cells. |
| ln Vivo |
Umbralisib hydrochloride (150 mg/kg, daily p.o.) significantly reduces 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].
In vivo, Umbralisib hydrochloride (150 mg/kg, daily oral) significantly reduces 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. The compound has demonstrated efficacy in clinical trials for various B-cell malignancies, leading to its FDA approval for marginal zone lymphoma and follicular lymphoma. |
| 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.
In vitro enzyme assays for PI3Kδ inhibition typically involve incubating recombinant PI3Kδ kinase with phosphatidylinositol-4,5-bisphosphate (PIP2) and ATP in the presence of varying concentrations of Umbralisib hydrochloride. The production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) is measured using HTRF or luminescent assays. IC₅₀ values are calculated from dose-response curves. |
| Cell Assay |
Multiple Myeloma resistant (MM-1R) or sensitive (MM-1S) cells are incubated with desired concentrations of RP5264. Growth is assessed after 96 h by a MTT assay.
Cellular assays are performed using lymphoma and leukemia cell lines, such as DLBCL or CLL cells. Cells are treated with Umbralisib hydrochloride at various concentrations for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. PI3K/AKT pathway inhibition is confirmed by Western blot analysis of phospho-AKT (Ser473) and phospho-PRAS40. c-Myc expression is measured by Western blot or qPCR. |
| Animal Protocol |
Oral gavage
In vivo studies are conducted in xenograft mouse models of lymphoma or leukemia. Umbralisib hydrochloride is administered orally at various doses (e.g., 150 mg/kg daily). Tumor volume is measured periodically, and tumors are harvested for biomarker analysis, including assessment of phospho-AKT and Ki-67 by immunohistochemistry. |
| ADME/Pharmacokinetics |
Umbralisib hydrochloride (molecular weight 608.01, formula C₃₁H₂₅ClF₃N₅O₃) is a small-molecule compound. It is orally bioavailable and soluble in DMSO. The compound is typically stored at -20°C. Its physicochemical properties support oral administration and favorable drug-like characteristics.
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| Toxicity/Toxicokinetics |
Preclinical and clinical toxicity studies have evaluated Umbralisib hydrochloride in animals and humans. As a PI3Kδ inhibitor, its toxicity profile includes immune-related adverse events such as infections, diarrhea, and hepatotoxicity. The compound was approved by the FDA in 2021 with a manageable safety profile. Common adverse events include diarrhea, fatigue, nausea, and neutropenia.
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| References |
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| Additional Infomation |
Umbralisib hydrochloride (TGR-1202; Ukoniq) is a dual PI3Kδ and CK1ε inhibitor approved by the FDA in 2021 for the treatment of marginal zone lymphoma and follicular lymphoma. Its mechanism involves inhibition of PI3Kδ, blocking B-cell receptor signaling and survival pathways, and inhibition of CK1ε, which further contributes to its anticancer activity. Umbralisib is the first PI3Kδ inhibitor approved for marginal zone lymphoma and represents an important therapeutic option for patients with these B-cell malignancies.
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| Molecular Formula |
C31H25CLF3N5O3
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|---|---|
| Molecular Weight |
608.01011633873
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| Exact Mass |
607.159
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| Elemental Analysis |
C, 61.24; H, 4.14; Cl, 5.83; F, 9.37; N, 11.52; O, 7.89
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| CAS # |
1532533-78-0
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| Related CAS # |
Umbralisib;1532533-67-7;Umbralisib R-enantiomer;1532533-69-9;Umbralisib tosylate;1532533-72-4;Umbralisib sulfate;1532533-75-7
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| PubChem CID |
90030289
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
43
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl.FC1C=CC2=C(C=1)C(C(C1C=CC=C(C=1)F)=C([C@H](C)N1C3C(=C(N)N=CN=3)C(C3C=CC(=C(C=3)F)OC(C)C)=N1)O2)=O
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| InChi Key |
QGVUVMVWYWMZIR-NTISSMGPSA-N
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| InChi Code |
InChI=1S/C31H24F3N5O3.ClH/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);1H/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;hydrochloride
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| Synonyms |
TGR-1202 hydrochloride; TGR 1202 hydrochloride; TGR1202 hydrochloride; TGR-1202 HCl; TGR 1202 HCl; TGR1202 HCl
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: ≥150 mg/mL (~246.7 mM)
H2O: <0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.11 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6447 mL | 8.2235 mL | 16.4471 mL | |
| 5 mM | 0.3289 mL | 1.6447 mL | 3.2894 mL | |
| 10 mM | 0.1645 mL | 0.8224 mL | 1.6447 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 | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03269669 | Recruiting | Procedure: Biopsy Drug: Umbralisib |
Grade 1 Follicular Lymphoma Grade 2 Follicular Lymphoma |
National Cancer Institute (NCI) |
August 10, 2017 | Phase 2 |
 The PI3Kδ inhibitor TGR-1202 is active in lymphomamodels.Blood.2017 Jan 5;129(1):88-99. |
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 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. |
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