Regulated Cell Death Modulators

InvivoGen offers a collection of small molecules known to modulate the activity of key players involved in regulated cell death pathways.

Modulators of Ferroptotic cell death

• RSL3

RSL3 (RAS-selective lethal 3) is a potent inducer of ferroptosis that directly inhibits GPX4, a key enzyme responsible for reducing lipid peroxides and maintaining redox balance in cells. By inactivating GPX4, RSL3 induces the accumulation of toxic amounts of reactive oxygen species (ROS) and subsequent oxidative membrane damage.

• Ferrostatin-1

Ferrostatin-1 functions by scavenging lipid peroxyl radicals and preventing oxidative membrane damage, thereby protecting cells from iron-dependent oxidative stress and subsequent ferroptotic cell death.

Inducers of pyroptotic cell death

• Val-boroPro

Val-boroPro (VbP, Talabostat), a dipeptide boronic acid, is a non-selective inhibitor of various dipeptidyl peptidases (DPPs) including DPP4, DPP8, and DPP9. It disrupts the inhibitory interaction between DPP8/9 and the inflammasome sensor NLRP1 (NLR family member, pyrin domain containing 1), leading to NLRP1 inflammasome formation, and subsequently cell death.

Inhibitors of pyroptotic cell death

• Ac-YVAD-cmk
• VX-765
• Z-VAD-FMK

These molecules are inhibitors of the inflammatory caspases (Caspase-1, Caspase-11/4/5) responsible for the cleavage of Gasdermin-D (GSDMD) and the release of its N-terminal domain (NT), which features pore-forming functions at the plasma membrane. Accumulation of GSDMD pores at the plasma membrane allows the passage of soluble cytosolic contents and ions, and ultimately, leads to plasma membrane rupture.

Learn more on pyroptosis

Modulators of necroptotic cell death

• BV6
• Necrostatin-1
• Z-IETD-FMK

These molecules target key players in TNF-induced necroptosis, the most studied and best-characterized necroptotic pathway.
Necrostatin-1 is a potent and selective inhibitor of the apoptosis and necroptosis initiator molecule RIPK1 (receptor-interacting serine/threonine-protein kinase 1). RIPK1-mediated cell death requires a loss/inhibition of cIAPs (cellular inhibitors of apoptosis proteins), which can be achieved using BV6, a specific antagonist of cIAPs. For full induction of necroptosis, concomitant blockade of the apoptosis initiator Caspase-8 is also required and can be achieved using Z-IETD-FMK.