TGR-1202 Tosylate

Names

[ Name ]:
TGR-1202 Tosylate

[Synonym ]:
TGR-1202 p-Tosylate
TGR-1202 4-methylbenzenesulfonate
(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 4-methylbenzenesulfonate

Biological Activity

[Description]:

Umbralisib (TGR-1202) tosylate 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 tosylate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib tosylate can be used for haematological malignancies reseach[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase

Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase

[Target]

PI3Kδ:6.2 nM (Kd)

CKIϵ:180 nM (Kd)

PI3Kγ:1400 nM (Kd)

PI3Kβ:>10000 nM (Kd)

PI3Kα:>10000 nM (Kd)

[In Vitro]

Umbralisib tosylate causes a half-maximal inhibition of human whole blood CD19 cell proliferation between 100-300 nM[3]. Umbralisib tosylate (10 nM-100 μM) inhibits phosphorylated AKT at Ser473 in a concentration-dependent manner in human lymphoma and leukemia cell lines[4]. Umbralisib tosylate (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]

Umbralisib tosylate (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].

[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 ]:
138 - 141 °C

[ Molecular Formula ]:
C₃₈H₃₂F₃N₅O₆S

[ Molecular Weight ]:
743.75100

[ Exact Mass ]:
743.20300

[ PSA ]:
171.81000

[ LogP ]:
9.56640

Related Compounds

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