Necrostatin-1 CAS NO.4311-88-0

necrostatin-1 is a specific rip1 inhibitor and inhibits tnf-α-induced necroptosis with ec50 of 490 nm.
ic50 value: 490 nm (ec50)
target: tnf-alpha
necrostatin-1 is an inhibitor of necroptosis, a mechanism of programmed cell death separate from apoptosis. necrostatin-1 functions as an allosteric inhibitor of the death domain receptor-associated adaptor kinase rip (rip1) in the necroptosis pathway. while affecting this distinct cell death pathway, necrostatin-1 does not present any perturbation of the fas/tnfr triggered canonical apoptosis cascade.
in vitro: shikonin-induced necroptosis can be reverted to apoptosis in the presence of necrostatin-1 (nec-1), a specific necroptosis inhibitor and that the death mode switch is at least partially due to the conversion from mitochondrial inner membrane permeability to mitochondrial outer membrane permeability, which is associated with bax translocation [1]. the cell viabilities inhibited by al could be enhanced by 3-ma, zvad-fmk and nec-1, of which nec-1 improved the cell viability most significantly. furthermore, the cell viability of neural cells treated with nec-1 increased concentration-dependently, and the expressions of cell death-related proteins were decreased also in a concentration-dependent manner [2].
in vivo: in a mouse model of myocardial infarction, survival of cmpcs 3 days after intra-myocardial injection was 39 ± 9% higher in cells pretreated with the nec-1 compound. however, the increase in cell number was not sustained over 28 days, and did not translate into improved cardiac function (ejection fraction %, 20.6 ± 2.1 vs. 21.4 ± 2.5 for vehicle and nec-1-treated cmpc, respectively) [3]. mice pretreated with nec-1 reduced the amount of pi-positive cells from 12 to 48 h after tbi. immunoblotting results showed that nec-1 suppressed tbi-induced beclin-1 and lc3-ii activation which maintained p62 at high level. nec-1 pretreatment also reversed tbi-induced bcl-2 expression and caspase-3 activation, as well as the ratio of beclin-1/bcl-2. both 3-ma and nec-1 suppressed tbi-induced caspase-3 activation and lc3-ii formation, z-vad only inhibited caspase-3 activation but increased lc3-ii expression at 24 h post-tbi [4].
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