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Biological Activity
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Description
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MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM in human SH-SY5Y cells. |
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Targets
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γ-secretase |
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IC50 |
5 nM [1] |
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In Vitro
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MK-0752 is identified as a moderately potent γ-secretase inhibitor, which reduces Aβ40 in a dose-dependent manner with an IC50 of 5 nM in human SH-SY5Y cells. [1] In vitro, MK-0752 blocks Notch-intracellular domain (ICD) cleavage and its subsequent nuclear translocation. [2] |
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In Vivo
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MK-0752 (240 mg/kg) reduces the generation of newly produced Aβ with 90% decrease of AUV in the brain of rhesus monkeys. In addition, MK-0752 treatment increases levels of Aβ 1–14, Aβ 1–15, and Aβ 1–16 , while decreases levels of Aβ 1–17. [1] In guinea-pigs, oral administration of MK-0752 (10 mg/kg -30 mg/kg) results in the dose-dependent reduction of Aβ40 in plasma, brain and cerebrospinal fluid (CSF) with IC50 of 440 nM in brain. [2] |
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Clinical Trials
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MK-0752 study has been completed in Phase I clinical trials in patients with Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors. |
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Features
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MK-0752 is a moderately potent γ-secretase inhibitor. |
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Combination Therapy
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Description
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Combination of MK-0752 and Docetaxel is currently in Phase I/II clinical trials in patients with Locally Advanced or Metastatic Breast Cancer. |
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Protocol
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Animal Study
[1]
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| Animal Models |
Cisterna Magna Ported (CMP) Rhesus Monkey Model. |
| Formulation |
MK-0752 is dissolved in water. |
| Doses |
≤240 mg/kg |
| Administration |
Administered via p.o. |
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