Umbralisib

SKU: orb1226140

Description

Umbralisib (RP5264,TGR1202, TGR-1202) is a potent, selective, orally available PI3Kδ inhibitor with IC50 of 22 nM, 50-fold selectivity over PI3Kα/β and >10,000 fold over PI3Kγ; enhances Brentuximab Vedotin-induced Hodgkin lymphoma cell death via mitotic arrest, demonstrates highly synergistic effect with the proteasome inhibitor carfilzomib in lymphoma, leukemia, and myeloma cell lines and primary lymphoma and leukemia cells; synergistically disrupts the 4E-BP1-eIF4F-c-Myc axis with carfilzomib, also potently inhibits 60% of the activity of CK1ε at 1 uM.Blood Cancer Phase 3 Clinical(In Vitro):Umbralisib causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM.Umbralisib (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines.Umbralisib (15-50 μM) potently represses the expression of c-Myc in the DLBCL cell line LY7, and is uniquely characterized with structural features suitable for targeting CK1ε in lymphoma cells.(In 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.

Key Properties

• CAS Number: 1532533-67-7
• MW: 571.5492
• Purity: >98% (HPLC)
• Formula: C₃₁H₂₄F₃N₅O₃
• SMILES: O=C1C(C2=CC=CC(F)=C2)=C([C@@H](N3N=C(C4=CC=C(OC(C)C)C(F)=C4)C5=C(N)N=CN=C53)C)OC6=CC=C(F)C=C16
• Target: PI3K
• Solubility: 10 mM in DMSO

Bioactivity

• In 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.
• In Vitro:
  Umbralisib causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM. Umbralisib (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines. Umbralisib (15-50 μM) potently represses the expression of c-Myc in the DLBCL cell line LY7, and is uniquely characterized with structural features suitable for targeting CK1ε in lymphoma cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RP 5264 | TGR1202 | TGR-1202

Quick Database Links

Gene Symbol

PI3K