Umbralisib

Research use only, not for human use.

Umbralisib (RP5264,TGR1202, TGR-1202) is a potent, selective, orally available PI3Kδ inhibitor with IC50 of 22 nM.

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.

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.

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.

RP 5264 | TGR1202 | TGR-1202

PI3K/Akt/mTOR signaling

PI3K

PI3Kδ

Cancer

Blood cancer

1532533-67-7

571.5492

C31H24F3N5O3

>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

4H-1-Benzopyran-4-one, 2-[(1S)-1-[4-amino-3-[3-fluoro-4-(1-methylethoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)-

(-20℃)

With Ice Pack

≥ 2 years