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TG101348 (SAR302503), JAK2 and BRD4 Dual Inhibitor

TG101348 (SAR302503), JAK2 and BRD4 Dual Inhibitor

$109.00
TG101348 is a potent, specific and orally bioavailable inhibitor of JAK2 and BRD4 in clinical trials.
Catalog No. Unit Price Qty
M60172-5s 5 mg solid $109.00

Details

Product Information
Molecular Weight: 524.68
Formula: C27H36N6O3S
Purity: ≥98%
CAS#: 936091-26-8
Solubility: DMSO up to 100 mM
Chemical Name: N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide
Storage: Powder: 4oC 1 year. DMSO: 4oC 3 month; -20oC 1 year.

Biological Activity:
TG101348 is a potent, specific and orally bioavailable inhibitor of JAK2 (IC50 ~3 nM) and BRD4 (IC50 ~164 nM). It is 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. It also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells, but not in normal human dermal fibroblasts at concentrations up to 10 uM, and its antiproliferative IC50 against fibroblasts is > 5 uM. In a UT7/EPO cell line, TG101348 inhibited STAT5 phosphorylation at 600 nM and inhibited AKT phosphorylation while reducing GATA-1 S310 phosphorylation. It also displaces BRD4 from chromatin and suppresses c-Myc expression. The combination of inhibitory activities on independent kinase and bromodomain oncogenic pathways exemplifies a new strategy for rational single-agent polypharmacological targeting.


How to Use:

  • In vitro: TG101348 was used at 1 µM in vitro.
  • In vivo: TG101348 was dosed to mice orally at 120 mg/kg twice per day in xenograft models.


Reference:

  1. 1. Wernig G, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. (2008) Cancer Cell. 13(4):311-20.
  2. 2. Geron I, et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. (2008) Cancer Cell. 13(4):321-30.
  3. 3. Lasho T, et al. Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. (2010) Leukemia. 24(7):1378-80.
  4. 4. Ciceri P, et al. Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. (2014) Nat Chem Biol. In press.



Products are for research use only. Not for human use.

Description

Details

Product Information
Molecular Weight: 524.68
Formula: C27H36N6O3S
Purity: ≥98%
CAS#: 936091-26-8
Solubility: DMSO up to 100 mM
Chemical Name: N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide
Storage: Powder: 4oC 1 year. DMSO: 4oC 3 month; -20oC 1 year.

Biological Activity:
TG101348 is a potent, specific and orally bioavailable inhibitor of JAK2 (IC50 ~3 nM) and BRD4 (IC50 ~164 nM). It is 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. It also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells, but not in normal human dermal fibroblasts at concentrations up to 10 uM, and its antiproliferative IC50 against fibroblasts is > 5 uM. In a UT7/EPO cell line, TG101348 inhibited STAT5 phosphorylation at 600 nM and inhibited AKT phosphorylation while reducing GATA-1 S310 phosphorylation. It also displaces BRD4 from chromatin and suppresses c-Myc expression. The combination of inhibitory activities on independent kinase and bromodomain oncogenic pathways exemplifies a new strategy for rational single-agent polypharmacological targeting.


How to Use:

  • In vitro: TG101348 was used at 1 µM in vitro.
  • In vivo: TG101348 was dosed to mice orally at 120 mg/kg twice per day in xenograft models.


Reference:

  1. 1. Wernig G, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. (2008) Cancer Cell. 13(4):311-20.
  2. 2. Geron I, et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. (2008) Cancer Cell. 13(4):321-30.
  3. 3. Lasho T, et al. Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. (2010) Leukemia. 24(7):1378-80.
  4. 4. Ciceri P, et al. Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. (2014) Nat Chem Biol. In press.



Products are for research use only. Not for human use.

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