C188-9 Chemical Properties

Boiling point:

680.9±65.0 °C(Predicted)

Density 

1.416±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:5): 0.16 mg/ml

form 

A crystalline solid

pka

8.14±0.50(Predicted)

color 

Off-white to pink

C188-9 Usage And Synthesis

Uses

C188-9 (TTI-101) is a STAT3 inhibitor, with a Kd of 4.7 nM. C188-9 inhibits G-CSF-induced STAT3 activation and STAT3-dependent gene expression. C188-9 induces apoptosis in AML cell lines and primary samples and inhibits colony formation by primary AML blasts[1][2][3][4].

Biological Activity

C188-9 (TTI 101) is a potent STAT3 inhibitor, binds STAT3 with high affinity, Kd=4.7±0.4 nM. It is well tolerated in mice, has good oral bioavailability, and is mainly enriched in tumor tissues.

in vitro

C188-9 is a small molecule inhibitor of STAT3, targeting the phosphotyrosine peptide binding site in the SH2 region of STAT3 with a Ki value of 136 nM. It does not inhibit upstream Jak or Src kinases.

in vivo

C188-9 inhibited tumor growth in mice bearing UM-SCC-17B xenografts after administration of C188-9. C188-9 was well tolerated in mice, had good oral bioavailability, and was concentrated in tumor tissue after administration.

target

IC 50

STAT3: 4.7 nM (Kd)

References

[1] Silva KA, et al. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia. J Biol Chem. 2015 Apr 24;290(17):11177-87. DOI:10.1074/jbc.M115.641514
[2] Redell MS, et al. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011 May 26;117(21):5701-9. DOI:10.1182/blood-2010-04-280123
[3] Bharadwaj U, et al. Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell carcinoma. Oncotarget. 2016 May 3;7(18):26307-30. DOI:10.18632/oncotarget.8368
[4] Redell MS, et al. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011;117(21):5701-5709. DOI:10.1182/blood-2010-04-280123