Sodium thiosulfate (sodium thiosulphate/STS) is a chemical and medication. As a medication, it is used in combination with sodium nitrite under the trade name to NITHIODOTE treat cyanide poisoning. The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN- ), which is relatively nontoxic and readily excreted in the urine. Sodium thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide. In addition, Sodium thiosulfate is used in calciphylaxis in hemodialysis patients with end-stage kidney disease. Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles. Sodium thiosulfate is used as treatment due to its antioxidant activity and as a chelating. Sodium thiosulfate renders renal protection by modulating the mitochondrial KATP channel for preventing urolithiasis. Moreover, STS was assumed to play a vital role in on ischemia reperfusion injury (IR). The effectiveness of STS as a cardioprotective agent was attributed to the reduction of apoptosis by binding to the active site of caspase-3 in silico, which was substantiated by the reduced expression of caspase-3 and poly ADP ribose polymerase levels.

Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. In 2015, a phase I clinical trial of PAC-1 opened for enrollment of cancer patients, and in 2016, it was announced that PAC-1 had been granted Orphan Drug Designation for treatment of glioblastoma by the FDA.

Aloxistatin (E64d) is an irreversible and membrane-permeable cysteine protease inhibitor. Aloxistatin was developed for treating muscular dystrophy. Open trials on 73 Duchene’s muscular dystrophy patients were conducted for 3 years at four Japanese national sanatoriums and resulted in some muscle strength improvement but the results were inconclusive and final double-blind studies did not confirm the results. Taisho has discontinued development of aloxistatin for the potential treatment of muscular dystrophy. The  trials completed through Phase 3. In animal models Aloxistatin (100 mg/kg, p.o.) strongly inhibits the cathepsin B&L activities in the skeletal muscle, heart and liver of hamsters. In spinal cord injury (SCI) rats, Aloxistatin provides neuroprotection in SCI lesion and penumbra.Aloxistatin reduces brain amyloid-β and improves memory deficits in Alzheimer's disease animal models by inhibiting cathepsin B activity.

Levistolide A is a naturally occurring compound isolated from Ligusticum chuanxiong Hort, which is used in traditional Chinese medicine to treat cancer. Levistolide has been studied in vitro against cell models for colon cancer and breast cancer. It was effective at inducing ER programmed apoptosis in colon cancer cells. In a cell model for breast cancer, levistolide was shown to enhance the apoptotic effects of adriamycin and vincristine. The effect of levistomide is correlated with cleavage of poly(ADP-ribose) polymerase PARP and up-regulation of caspase-3.

MDL-201053, (DL-ALANINE)- (Z-FA-FMK) is an irreversible inhibitor of cysteine proteases, such as cathepsin B, L, and S. The compound has also inhibitited papain and cruzain. Z-FA-FMK has been shown to selectively inhibit effector caspase-2, caspase-3, caspase-6, and caspase-7 without affecting initiator caspase-8 and caspase-10 while showing minimal toxicity to normal mammalian cells in vitro. Due to Z-FA-FMK's effector caspase specificity, the compound has been recorded to inhibit some forms of caspase mediated apoptosis. The compound has been observed to be an effective in time dependent inactivation of cathepsin B isozymes from a number of tissues. Studies show Cathepsin B-like activity plays a role in the cascade of proteolytic cartilage destruction. Z-FA-FMK is an inhibitor of cathepsin H. This compound has been shown to block the production of IL1-α, IL1-β, and TNF-α induced by LPS in macrophages by inhibiting NF-κB pathways. Z-FA-FMK blocks not only NF-kappaB activation but inhibits, also, T cell blast formation, and prevents cells from entering and leaving the cell cycle revealing demonstrating immunosuppressive abilities. Z-FA-FMK is a very effective viral inhibitor that can prevent reovirus replication in vitro and reovirus-mediated myocarditis, as well as reovirus-mediated oncolysis, in vivo.

Aflatoxin G1 ((7aR,10aS)-3,4,7a,10a-tetrahydro-5-methoxy-1H,12H-furo[3',2':4,5]furo[2,3-h]pyrano[3,4-c][1]benzopyran-1,12-dione) is a food contaminant produced by various species of the common soil fungus, Aspergillus and is associated with toxicity and hepatocarcinogenicity in human and animal populations. Epidemiological studies have shown that Aflatoxin G1 is one of the most frequently detected contaminating mycotoxins in grains and foodstuffs in areas with high-incidence of lung and esophageal cancer

Esculetin (aka Aesculetin) is a derivative of coumarin. It is a naturally occurring lactone which is present in chicory and in many toxic medicinal plants; often found in a glycosidic form or conjugated to caffeic acids. It is used as an ingredient in some sunscreens, but there is evidence that it acts as a photosensitizer for DNA damage. Esculetin has been investigated in a number of cellular and animal cancer models, and for other conditions such as dry eyes.

Beta-sitosterol is one of the main dietary phytosterols found in plants which have a similar skeleton as cholesterol. In human clinical trials, beta-sitosterol has been shown to have cholesterol-lowering effects and to relieve symptoms of benign prostatic hyperplasia. There has been a large amount of basic research conducted for potential applications of beta-sitosterol in a diverse range of conditions including cervical cancer, breast cancer, cystic fibrosis, and others. Beta-sitosterol is available over the counter as a natural health supplement and is marketed for a wide range of applications including headaches, tuberculosis, allergies, cancers, fibromyalgia, lupus, asthma, hair loss and many others.

Naringin is a flavanone plant metabolite which found in citrus fruits and in quantitatively significant amounts from grapefruit in particular. Naringin has attracted attention as a dietary supplement purported to aid in fat and weight loss. Ingestion of naringin and related flavonoids can interfere with the absorption and metabolism of certain drugs, and therefore consumption of grapefruit juice with medication is advised against. Naringin possesses numerous biological properties such as antioxidant, anti-inflammatory, and anti-apoptotic activity. It has been extensively studied in pre-clinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders, and several different cancer models.

Tangeretin is an O-polymethoxylated flavone that is found in tangerine and other citrus peels. Its natural role is to strengthen the cell wall and act as a plant's defensive mechanism against disease-causing pathogens. Animal studies have shown the potential fo tangeretin as a therapeutic in a number of conditions including cancers, asthma, CKD, hypercholesterolemia, and Parkinson's disease.