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Chemical Structure| 936091-14-4 Chemical Structure| 936091-14-4

Structure of TG101209
CAS No.: 936091-14-4

Chemical Structure| 936091-14-4

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TG 101209 is a potent and selective JAK2 inhibitor with IC50 of 6 nM, also inhibits Flt3 and RET with IC50 values of 25 nM and 17 nM, respectively.

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Product Details of TG101209

CAS No. :936091-14-4
Formula : C26H35N7O2S
M.W : 509.67
SMILES Code : O=S(C1=CC=CC(NC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3)=NC=C2C)=C1)(NC(C)(C)C)=O
MDL No. :MFCD15528085
InChI Key :JVDOKQYTTYUYDV-UHFFFAOYSA-N
Pubchem ID :16722832

Safety of TG101209

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of TG101209

epigenetics
RTK
JAK-STAT

Isoform Comparison

Biological Activity

Target
  • JAK3

    JAK3, IC50:169 nM

  • JAK2

    JAK2, IC50:6 nM

  • c-RET

    RET, IC50:17 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MM1.S 5 µM 6, 24, 48 hours Induction of apoptosis Am J Hematol. 2010 Sep;85(9):675-86.
RPMI 8226 5 µM 6, 24, 48 hours Induction of apoptosis Am J Hematol. 2010 Sep;85(9):675-86.
Caki-1 6 nM 1 day To validate the inhibitory effect of TG-101209 on BUB1B EBioMedicine. 2022 Apr;78:103963.
U266 5 µM 48 hours Preferential killing of CD45+ cells Am J Hematol. 2010 Sep;85(9):675-86.
SET-2V617F cells 0.125–2 µM 48 hours TG101209 induced dose-dependent apoptosis Cell Rep. 2013 Nov 27;5(4):1047-59.
TEL-JAK2 T-ALL cells 0.125–4 µM 24 hours To evaluate the killing effect of TG101209 on TEL-JAK2 T-ALL cells, the results showed that TG101209 induced dose-dependent apoptosis. Cell Rep. 2013 Nov 27;5(4):1047-59.
SET-2V617F cells 0.125–2 µM 24 hours To evaluate the killing effect of TG101209 on SET-2V617F cells, the results showed that TG101209 induced dose-dependent apoptosis. Cell Rep. 2013 Nov 27;5(4):1047-59.
HCC2429 1 µM 24-48 hours Inhibited STAT3 phosphorylation and survivin expression, sensitized cells to radiation J Thorac Oncol. 2011 Apr;6(4):699-706.
CD34+ CML cells 100 nM 3 days To evaluate the growth inhibitory effect of TG101209 on CD34+ CML cells, results showed that TG101209 significantly inhibited the growth of CD34+ CML cells. J Natl Cancer Inst. 2013 Mar 20;105(6):405-23.
H460 3 µM 48 hours Inhibited STAT3 phosphorylation and survivin expression, sensitized cells to radiation J Thorac Oncol. 2011 Apr;6(4):699-706.
Ba/F3-JAK2-V617F cells 10 nM, 15 nM, 20 nM 48 hours Induced apoptosis in Ba/F3-JAK2-V617F cells Clin Cancer Res. 2011 Dec 1;17(23):7347-58.
K562 cells 0.5 µM 48 hours To evaluate the growth inhibitory effect of TG101209 on K562 cells, results showed that TG101209 significantly inhibited the growth of K562 cells. J Natl Cancer Inst. 2013 Mar 20;105(6):405-23.
BaF3-EPOR cells 0.6 µM TG101209 mildly inhibited colony formation of BaF3-EPOR cells plated on methylcellulose containing a sub-saturating EPO concentration. Nat Med. 2011 Jun 19;17(7):845-53.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice Lung cancer xenograft model Oral 100 mg/kg Twice daily for 7 consecutive days Combination of TG101209 and radiation significantly extended tumor growth delay, increased apoptosis, and reduced tumor proliferation and vascular density J Thorac Oncol. 2011 Apr;6(4):699-706.
Mice AE9a leukemia mouse model Oral 100 mg/kg Twice daily for two weeks TG101209 effectively reduced tumor burden in AE9a leukemia mice and significantly prolonged survival. Leukemia. 2013 Dec;27(12):2272-9
Mice TEL-JAK2 T-ALL model Oral 100 mg/kg bid Twice daily for 4 days To evaluate the therapeutic effect of TG101209 on TEL-JAK2 T-ALL model mice, the results showed that TG101209 significantly reduced tumor cells in peripheral blood and spleen and prolonged the survival of mice. Cell Rep. 2013 Nov 27;5(4):1047-59.
Mice TEL-JAK2 T-ALL model Oral 100 mg/kg bid Twice daily for 4 days TG101209 significantly reduced tumor cells in peripheral blood and spleen and prolonged the survival of mice Cell Rep. 2013 Nov 27;5(4):1047-59.
Mice VhlR200W/R200W knock-in mice Oral gavage 100mg/kg Twice daily for 5 weeks TG101209 treatment reversed the disease phenotype in vhlR200W/R200W knock-in mice, reducing hematocrit (Hct) levels and decreasing the number of megakaryocytes in the spleen. Nat Med. 2011 Jun 19;17(7):845-53.
Mice NOD/SCID–IL2Rγ-deficient mice Oral 60 mg/kg Twice a day for 2 weeks To evaluate the effect of combined treatment with TG101209 and imatinib on the survival of leukemic mice, results showed that the combination treatment significantly prolonged the survival of mice. J Natl Cancer Inst. 2013 Mar 20;105(6):405-23.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.81mL

1.96mL

0.98mL

19.62mL

3.92mL

1.96mL

References

 

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