Umbralisib hydrochloride  (Synonyms: TGR-1202 hydrochloride; RP5264 hydrochloride)

Umbralisib (TGR-1202) hydrochloride is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC₅₀ of 22.2 nM and 6.0 μM, respectively. Umbralisib hydrochloride exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib hydrochloride can be used for haematological malignancies reseach^[1][2][3][4].

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 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^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Umbralisib hydrochloride (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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

608.01

Solid

C₃₁H₂₅ClF₃N₅O₃

1532533-78-0

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.[H]Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Maharaj K, et al. The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells. Blood Adv. 2020 Jul 14;4(13):3072-3084.  [Content Brief]

  [2]. Burris HA 3rd, et al. Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 2018 Apr;19(4):486-496.  [Content Brief]

  [3]. Swaroop Vakkalankaa, et al. Inhibition of PI3Kδ kinase by a selective, small molecule inhibitor suppresses B-cell proliferation and leukemic cell growth.

  [4]. Deng C, et al. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies. Blood. 2017 Jan 5;129(1):88-99  [Content Brief]