Molecule

Description

Solid tumours

Description

TAK-733 is a potent, selective, non ATP-competitive MEK inhibitor with IC50 of 3.2 nM.

Targets

IC₅₀

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.

Features

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]

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