| Bioactivity | NGP555 is a γ-secretase modulator. | ||||||||||||
| Target | γ-secretase | ||||||||||||
| Invitro | NGP555 potently lowers Aβ42 in cell cultures (9 nM) while increasing shorter forms of Aβ[1]. | ||||||||||||
| In Vivo | NGP555 significantly lowers Aβ42 in the cerebrospinal fluid (CSF) at time points from 8 to10 hours post dose, panel B shows that reduction of Aβ cerebrospinal fluid (CSF) levels is significant at 3.75 mg/kg of NGP555 and above, and panel C shows an increase in Aβ38 levels at 15 mg/kg of NGP555 and above. When combining the reduction of Aβ42 with an increase in Aβ38, NGP555 is effective at raising CSF Aβ38/42 ratio at 1.87 mg/kg and above (panel D). NGP555-treated Tg mice show a significant protection from decline in performance with >65% less decline (P<0.005) when comparing the differential of Tg to non-Tg vehicle-treated mice. NGP555 also shows good oral bioavailability and is brain-penetrant with a brain:plasma ratio of ~0.93 in mice[1]. | ||||||||||||
| Name | NGP555 | ||||||||||||
| CAS | 1304630-27-0 | ||||||||||||
| Formula | C23H23FN4S | ||||||||||||
| Molar Mass | 406.52 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Kounnas MZ, et al. NGP 555, a γ-Secretase Modulator, Lowers the Amyloid Biomarker, Aβ42, in Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in Rodents. Alzheimers Dement (N Y). 2017 Jan;3(1):65-73. |