Umbralisib

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.

1532533-67-7

RP 5264 | TGR1202 | TGR-1202

Pharmacology & Drug Discovery

>98% (HPLC)

10 mM in DMSO

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

C31H24F3N5O3

571.5492

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.