Interesting work breaking ... LinkGevity has developed LINK-001 as an anti-necrotic, supposedly it consists of "two FDA compounds which have other uses" which together prevent the necrotic damage done to cells from aging and space. More at https://www.uclscien....com/articleb57 of course since it is just two already approved drugs they are hiding the names as hard as they can but I did dig up some possibilities.
AI research warning! None of this is suggested. It just speculation for discussion, I'll seriously frown at anyone stupid enough to just start popping pills.
Its known they used AI to screen possible Ca++ blocker (what causes the cell to explode) and had been also working with Necrostatin-1s (Nec-1s) for inhibiting RIPK1/3 (a key driver of necroptosis), but that is not approved for human use ... but there are other RIPK1 inhibitors used in cancer. So it has to be a different approved drug that has been discovered to have "off-target" or secondary anti-necrotic/kinase-inhibiting properties (potentially certain anti-inflammatory or oncology drugs), rather than Necrostatin-1s itself.
So pretty good bet its a Ca++ blocker + RIPK1 inhibitor.
Doing my on AI candidate search some possibilities surfaced...
Calcium (Ca²⁺) Channel Modulation
Mechanism: In necrotic cell death, stressed cell membranes become permeable, allowing an "uncontrolled" influx of calcium from the extracellular space into the cytoplasm. This calcium surge triggers destructive enzymes that lead to "tissue rot".
Probable Drug Class: One component is likely a calcium antagonist (calcium channel blocker). Clinical studies have long suggested that certain calcium antagonists (like amlodipine or verapamil) can prevent calcium-flux-induced necrosis by inhibiting ion entry into mitochondria.
Necroptosis/Necrosis Inhibition
Mechanism: This component prevents the formation of "pores" in the cell membrane that would otherwise lead to total cell rupture. It blocks the RIPK1/RIPK3/MLKL pathway, which is responsible for forming the "necrosome"—a complex that punches holes in the cell membrane from the inside out.
Possible Repurposed Kinase Inhibitors: Some FDA-approved cancer or anti-inflammatory drugs, such as certain Janus Kinase (JAK) inhibitors or specialized tyrosine kinase inhibitors (e.g., Sunitinib derivatives), have shown off-target RIPK1 inhibitory activity and are candidates for repurposing.
Most Likely Candidate: Phensuximide
Phensuximide is an FDA-approved anticonvulsant that was recently identified (2025) as a potent and specific inhibitor of RIPK1 kinase activity.
Similarity to Nec-1: Computational screening of over 10,000 drug-like molecules found that Phensuximide is structurally similar to Necrostatin-1 and binds to the same key functional domains on the RIPK1 protein.
Mechanism: It stabilizes RIPK1 in its inactive conformation, preventing the autophosphorylation required to trigger necroptosis.
Clinical Potential: In animal models, it has demonstrated "robust and consistent protection" against systemic inflammation and tissue damage (like that seen in kidney injury).
Several cancer drugs are well-known to inhibit RIPK1 or RIPK3 as an off-target effect. These are frequently used in research as the "clinical versions" of necrostatins:
Pazopanib (Votrient): An FDA-approved drug for renal cell carcinoma that has been identified as a potent inhibitor of RIPK1.
Ponatinib (Iclusig): Approved for leukemia, this drug is a "dual inhibitor" that targets both RIPK1 and RIPK3, making it even more potent than Nec-1s in some cell models.
Sorafenib (Nexavar): Another multi-target TKI that blocks both RIPK1 and RIPK3. It has shown protective effects in models of kidney ischemia-reperfusion injury, similar to the goals of LinkGevity's program
Other Noteworthy Repurposing Candidates
Vemurafenib (Zelboraf): A BRAF inhibitor used for melanoma that was found (2023) to be an effective RIPK1 antagonist, binding to a distinct hydrophobic pocket to stabilize the protein in an inactive state.
Quizartinib (Vanflyta): Recently identified as a highly effective inhibitor of RIPK1 at low concentrations, showing protective effects against systemic inflammatory responses in mice.
Phenytoin: A common anti-epileptic medication that, like Phensuximide, belongs to the hydantoin class (the same class as Nec-1) and has been shown to inhibit RIPK1 and protect against ischemia-reperfusion-induced kidney injury.
Any biochem wiz want to comment?
Anyway it looks so promising there was scuttle-butt that Britain plans to add it as soon as possible to the NHS