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Research Area
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Description
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Solid tumours |
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Biological Activity
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Description
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TAK-733 is a potent, selective, non ATP-competitive MEK inhibitor with IC50 of 3.2 nM. |
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Targets
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MEK1/2 |
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IC50 |
3.2 nM [1] |
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In Vitro
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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] |
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In Vivo
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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] |
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Clinical Trials
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A Multicenter, Open-label, Dose-escalation, Phase I Study of TAK-733, an Oral MEK Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies. |
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Features
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Combination Therapy
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Description
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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] |
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Protocol
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Animal Study
[2]
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| 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 |
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