TAK-733

• Catalog No.: S2617
• CAS Number: 1035555-63-5
• M. F.: C17H15F2IN4O4
• M. W.: 504.2266764
• Storage: -20°C

SYNONYMS

• IUPAC name: 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-8-methyl-3H,4H,7H,8H-pyrido[2,3-d]pyrimidine-4,7-dione
• IUPAC Traditional name: 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-8-methylpyrido[2,3-d]pyrimidine-4,7-dione
• Synonyms: TAK733

DATABASE IDS

• CAS Number: 1035555-63-5

PROPERTIES

• Target: MEK
• Salt Data: Free Base
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Solid tumours

Biological Activity

• Description: TAK-733 is a potent, selective, non ATP-competitive MEK inhibitor with IC50 of 3.2 nM.
• Targets: MEK1/2
• IC50: 3.2 nM ^[1]
• In Vitro: 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. ^[1]
• 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. ^[1] TAK-733 shows maximally efficacious doses at once daily orally doses of 10 mg/kg. ^[2]
• Clinical Trials: A Multicenter, Open-label, Dose-escalation, Phase I Study of TAK-733, an Oral MEK Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies.

Combination Therapy

• Description: Alisertib at dose of 30 mg/kg combine with TAK-733 at dose of 10 mg/kg result in additive to synergistic antitumor activity and in prolonged inhibition of tumor regrowth in experimental human solid tumor xenograft models including NSCLC (NCI H23 [KRAS and LKB1 mutations]), CRC (SW620 [KRAS, APC, p53 mutations]), and pancreatic cancer (Panc 1 and Capan 1 [KRAS mutations] and BxPC-3 [No MAPK mutations]) models in immunocompromised mice. ^[2]

Protocol

• Protocol: Animal Study ^[2]
• Animal Models: 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: Saline
• Doses: 10 mg/kg
• Administration: Orally administrated once daily for 21 days

References

• References: [1] Qing Dong, et al. Bioorg Med Chem Lett, 2011, 21(5), 1315-1319.
• References: [2] Fabrey R, et al. AACR Annual Meeting, 2012, Abs 3739.

REFERENCES

• Qing Dong, et al. Bioorg Med Chem Lett, 2011, 21(5), 1315-1319.
• Fabrey R, et al. AACR Annual Meeting, 2012, Abs 3739.