TGR-1202 Sulfate
Names
[ CAS No. ]:
1532533-75-7
[ Name ]:
TGR-1202 Sulfate
[Synonym ]:
(S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one sulfate
Biological Activity
[Description]:
Umbralisib sulfate 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 sulfate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib sulfate can be used for haematological malignancies reseach[1][2][3][4].
[Related Catalog]:
[Target]
PI3Kδ:6.2 (Kd)
CK1ϵ:180 (Kd)
PI3Kγ:1400 (Kd)
PI3Kα:>10000 (Kd)
PI3Kβ:>10000 (Kd)
[In Vitro]
Umbralisib sulfatecauses a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM[3]. In human lymphoma and leukemia cell lines, Umbralisib sulfate (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner[4]. Umbralisib sulfate (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].
[In Vivo]
In a subcutaneous xenograft model of T-cell acute lymphoblastic leukemia (T-ALL) in NOD/SCID mice using the MOLT-4 cell line, Umbralisib sulfate (150 mg/kg, daily p.o.) significantly shrinks the tumors by day 25[4].
[References]
[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.
[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.
[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.
Chemical & Physical Properties
[ Melting Point ]:
125 - 127 °C
[ Molecular Formula ]:
C31H26F3N5O7S
[ Molecular Weight ]:
669.62800
[ Exact Mass ]:
669.15100
[ PSA ]:
192.04000
[ LogP ]:
7.67190