product name TAK-733
Description: TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. TAK-733 selectively binds to and inhibits the activity of MEK1/2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. TAK-733 has been reported to broadly inhibit tumor activity in mouse xenograft models of human cancer (melanoma, colorectal, NSCLC, pancreatic and breast cancer).
References: Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9.
504.23
Formula
C17H15F2IN4O4
CAS No.
1035555-63-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 101 mg/mL (200.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: TAK-733 is highly potent and selective MEK allosteric site inhibitor with IC50 of 3.2 nM. TAK-733 shows potent enzymatic and cell activity with an EC50 of 1.9 nM against ERK phosphorylation in cells. Kinase Assay: Cell Assay: TAK-733 showed broad activity in most melanoma cell lines with relative resistance observed at IC50 > 0.1 μmol/L in vitro. Moreover, Cell lines with a BRAF or KRAS mutation were associated with sensitivity to TAK-733 with an IC50 value of < 0.5μM. |
|---|---|
| In Vivo | TAK-733 demonstrates broad antitumor activity in mouse xenograft models of human cancer including models of melanoma, colorectal, NSCLC, pancreatic and breast cancer. TAK-733 is well tolerated with pharmacokinetics and pharmacodynamics that support once-daily oral dosing in humans. TAK-733 shows maximally efficacious doses at once daily orally doses of 10 mg/kg. |
| Animal model | Human solid tumor xenograft models including NSCLC (NCI H23 [KRAS and LKB1 mutations]), CRC (SW620 [KRAS, APC, p53 mutations]) Pancreatic cancer (Panc 1 and Capan 1 [KRAS mutations] and BxPC-3 [No MAPK mutations]) models in immunocompromised mice. |
| Formulation & Dosage | Dissolved in saline; 10 mg/kg; Oral gavage |
| References | Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9. |
