Description
7BIO is a derivative of indirubin that triggers a rapid cell death process that is distinct from apoptosis and devoid of cytochrome
c release or caspase activation. Furthermore, in contrast to other indirubin derivatives, 7BIO has only marginal activity against the classic indirubin targets, cyclin-dependent kinases and GSK3. Instead, 7BIO inhibits FLT3 (IC
50 = 0.34 μM) and the dual-specificity tyrosine phosphorylation-regulated kinases, DYRK1A and DYRK2 (IC
50s = 1.9 and 1.3 μM, respectively). It also inhibits Aurora B and C kinases with IC
50 values of 4.6 and 0.7 μM, respectively.
in vivo
7Bio (2.3, 7.0, and 23.3 μg/kg; bilateral ventricle injection) significantly attenuates Aβ oligomer-induced impairment of recognition, spatial learning and memory in mice[1].
7Bio (2.3, 7.0, and 23.3 μg/kg; bilateral ventricle injection) decreases Aβ oligomer-induced increase of TNF-α and IL-6 production in the brain and the expression of synapsin-1 and PSD-95 in the hippocampal region of mice[1].
7Bio (2.3, 7.0, and 23.3 μg/kg; bilateral ventricle injection) attenuates Aβ oligomer-induced increase expression of pTau, activation of microglia and astrogliosis in the brain of mice[1].
7Bio (2.3, 7.0, and 23.3 μg/kg; bilateral ventricle injection) prevents decreased expression of pSer9-GSK3β and has no significant effects on the Tau protein level[1].
| Animal Model: | 8 weeks mice (30 g)[1] |
| Dosage: | 2.3, 7.0, and 23.3 μg/kg |
| Administration: | bilateral ventricle injection |
| Result: | Attenuates Aβ oligomer-induced impairment of recognition, spatial learning and memory in mice. |
References
[1] ribas j, bettayeb k, ferandin y, et al. 7-bromoindirubin-3′-oxime induces caspase-independent cell death[j]. oncogene, 2006, 25(47): 6304-6318.
[2] myrianthopoulos v, kritsanida m, gaboriaud-kolar n, et al. novel inverse binding mode of indirubin derivatives yields improved selectivity for dyrk kinases[j]. acs medicinal chemistry letters, 2012, 4(1): 22-26.
[3] myrianthopoulos v, magiatis p, ferandin y, et al. an integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases b and c by a series of 7-substituted indirubins[j]. journal of medicinal chemistry, 2007, 50(17): 4027-4037.
