Apoptosis Inducers

Andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.

LY573636 is a potent anti-tumor agent, which causes growth arrest and apoptosis of a variety of human solid tumors in vitro and in vivo. LY573636-induced apoptosis occurs by a mitochondrial-targeted mechanism.

Homoharringtonine is a cephalotaxine alkaloid which inhibits the formation of diphenylalanine and acetylphenylalanyl-puromycin in liver ribosomes.

Difopein, dimeric version of R18 peptide that binds to 14.3.3 proteins with high affinity.

Episilvestrol is a derivative of Silvestrol, which can induce apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7; 5'myc-UTR-LUC inhibtior (IC50= 0.8 nM).

SMIP004 is a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells.

2,3 DCPE displays anticancer agent properties and induces ERK activation.

CHM 1 is a potent, selective antitumor agent in human hepatocellular carcinoma in vitro.

CFM 4, CARP-1 mimetic; interferes with CARP-1 binding to APC-2. Enhances CARP-1 expression and induces G2/M cell cycle arrest. Induces apoptosis and suppresses cell growth in cancer cells.

ONC212 is a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. ONC212 is active in pancreatic cancer as single agent or in combination with 5-fluorouracil, irinotecan, oxaliplatin or RTK inhibitor crizotinib.

NUN82647, also known as QBS or 2-Amino-N-quinolin-8-yl-benzenesulfonamide, is an Inhibitor of cell cycle at G2 phase; apoptosis inducer.

Cinchonine prevents High-Fat-Diet-Induced Obesity through downregulation of Adipogenesis and Adipose inflammation.

Calcium dobesilate, a vasoprotective, is widely used in chronic venous disease, diabetic retinopathy and the symptoms of haemorrhoidal attack in many countries.

Taurolidine is a broad-spectrum antimicrobial for the prevention of central venous catheter-related infections. Taurolidine has a direct and selective antineoplastic effect on brain tumor cells by the induction of apoptosis.

Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia.

Dihydrokaempferol is isolated from Bauhinia championii (Benth). Dihydrokaempferol induces apoptosis and inhibits Bcl-2 and Bcl-xL expression. Dihydrokaempferol is a good candidate for new antiarthritic drugs.

Destruxin B, isolated from entomopathogenic fungus Metarhizium anisopliae, is one of the cyclodepsipeptides with insecticidal and anticancer activities. Destruxin B induces apoptosis via a Bcl-2 Family-dependent mitochondrial pathway in human nonsmall cell lung cancer cells.

IV-23 (Compound 20) is a potent Noxa mediated apoptosis inducer, and it is a promising anticancer agent with potential. IV-23 inhibits cell growths in vitro and in vivo, reduces colony formation, arrests cell cycle at M phase, and induces esophageal squamous cell carcinoma (ESCC).

Flavokawain B (Flavokavain B) is a chalcone isolated from the root extracts of kava-kava plant and a potent apoptosis inducer for inhibiting the growth of various cancer cell lines.

Glycochenodeoxycholic acid (Chenodeoxycholylglycine) is a bile acid formed in the liver from chenodeoxycholate and glycine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. Glycochenodeoxycholic acid (Chenodeoxycholylglycine) induces hepatocyte apoptosis.

Darinaparsin, also know as ZIO-101 and SP-02, is a small-molecule organic arsenical with potential antineoplastic activity.

4-Oxo-4-HPR is an inhibitor of tubulin polymerization, inducing marked G2-M cell cycle arrest and apoptosis in fenretinide-sensitive and fenretinide-resistant cell lines. It is also a fenretinide metabolite.

epi-Eriocalyxin A is a diterpenoid compound that serves as an apoptosis inducer in colon cancer cells. It effectively inhibits the activation of ERK1/2 and JNK pathways, leading to the suppression of Bcl-2 expression. This compound is valuable for research focused on cancer treatment and the mechanisms of apoptosis.

Sanguinarine chloride is a benzophenanthridine alkaloid that functions as an apoptosis inducer primarily through the generation of reactive oxygen species (ROS). This compound is known to activate key signaling pathways, specifically JNK and NF-κB, facilitating programmed cell death. Sanguinarine chloride is widely utilized in cancer research and studies investigating apoptotic mechanisms.

Dimethyl tetrasulfide (1,4-Dimethyltetrasulfane) is an apoptosis inducer that specifically targets leukemia cells. It demonstrates cytotoxic effects by promoting the production of intracellular reactive oxygen species (ROS) and activating the caspase-3 enzyme. This compound is valuable for research into cancer therapies, particularly in the context of leukemia.

9-cis-Canthaxanthin is a carotenoid recognized for its pro-apoptotic properties, particularly in THP-1 macrophage cells. This compound induces apoptosis by enhancing the activity of caspase-3 and caspase-8, making it a valuable tool for studying apoptosis pathways and cellular responses in various research applications.

Euptox A (9-Oxo-10, 11-dehydroageraphorone) is a potent apoptosis inducer derived from the cadenine sesquiterpene found in Eupatorium adenophorum. It enhances the expression of apoptotic proteases, particularly caspase-10, in HeLa cells, leading to increased apoptotic activity. This compound is valuable for research into apoptosis mechanisms and potential therapeutic applications in cancer treatment.

MT-21 is an apoptosis inducer that functions as an inhibitor of adenine nucleotide translocase. It triggers apoptosis by activating c-Jun N-terminal kinase (JNK) through the Krs/MST signaling pathway and facilitates the activation of caspase-3 via caspase-9. Additionally, MT-21 promotes the release of cytochrome c from mitochondria, making it a valuable reagent for investigating tumor biology and apoptotic mechanisms in cancer research.

SM1044 is a dihydroartemisinin (DHA) dimer that serves as an apoptosis inducer. It activates caspase pathways to effectively trigger apoptosis in RL95-2 and KLE cancer cell lines. Additionally, SM1044 demonstrates potent antiproliferative activity, with IC50 values below 3.6 μM across multiple cancer cell lines, including HEC-50, HEC-1-A, HEC-1-B, and AN3CA. Furthermore, SM1044 has been shown to inhibit tumor growth in RL95-2 xenograft mouse models, highlighting its potential utility in cancer research.

Ly101-4B is an apoptosis inducer that primarily targets the regulation of key proteins involved in cell survival and proliferation. It exhibits significant antiproliferative and cytotoxic effects by reducing HSF1 expression and inhibiting microRNA-214 synthesis, leading to the downregulation of HSP27, HSP70, and HSP90. Additionally, Ly101-4B activates caspase 3/7-mediated apoptosis by impairing DNA synthesis and disrupting the cell cycle at the G1/S phase transition, while sparing RNA synthesis and avoiding necrosis. This compound is particularly effective against pancreatic ductal adenocarcinoma cells with distinct genotypes and levels of E2F dependence, making it valuable for research in epithelial ovarian cancer and pancreatic ductal adenocarcinoma.

Antitumor agent-72 is a potent apoptosis inducer targeting key apoptotic pathways. This compound effectively activates caspase-3 and induces PARP cleavage, leading to significant anticancer activity. Antitumor agent-72 is suitable for studies related to cancer research and the exploration of apoptosis mechanisms.

3-Methoxy-9H-Carbazole is a potent apoptosis inducer that primarily targets caspase-3 activity. This compound enhances the generation of reactive oxygen species, leading to the inhibition of cancer cell proliferation and the initiation of apoptotic pathways. Its biological activity makes it a valuable tool for research into cancer mechanisms and apoptosis-related studies.

cRIPGBM is a proapoptotic derivative of RIPGBM that selectively induces apoptosis in glioblastoma (GBM) cancer stem cells by targeting receptor-interacting protein kinase 2 (RIPK2). It demonstrates an EC50 of 68 nM in GBM-1 cells, making it a valuable tool for studying apoptosis mechanisms in cancer research. This compound has potential applications in investigating therapeutic strategies for GBM by promoting cell death in cancer stem cell populations.

Xanthoangelol is an apoptosis inducer derived from Angelica keiskei, known for its ability to trigger programmed cell death in neuroblastoma and leukemia cells. It also exhibits anti-inflammatory properties by suppressing obesity-related inflammatory responses and demonstrates antibacterial activity. Additionally, Xanthoangelol inhibits monoamine oxidases, contributing to its diverse biological effects, making it suitable for research in cancer therapeutics and inflammatory disease models.

28-Deoxonimbolide is a limonoid derived from Azadirachta indica, functioning as an apoptosis inducer. This compound exhibits significant anticancer activity by inducing apoptotic cell death in HL60 cells through both mitochondrial and death receptor-mediated pathways. Its ability to trigger these mechanisms makes it a valuable tool for research in cancer biology and apoptosis.

Gomisin N, a lignan compound derived from Schisandra chinensis, functions primarily as an apoptosis inducer. It has demonstrated the ability to activate key signaling pathways such as AMPK, Akt, MAPK/ERK, and Nrf2, while also promoting the activation of caspase-3 and PARP-1. Gomisin N exhibits a range of biological activities including anti-inflammatory, antioxidant, anti-obesity, anti-diabetic, and anti-melanogenesis effects, and has shown potential in inhibiting proinflammatory cytokines. Additionally, it possesses anti-tumor properties, particularly against cervical and liver cancers, and may offer benefits in the context of Alzheimer’s disease research.

Hellebrigenin is an apoptosis inducer that selectively inhibits the MAPK signaling pathway, including ERK, p38, and JNK, as well as XIAP. It plays a critical role in activating intrinsic apoptosis mechanisms, including mitochondrial membrane potential disruption, activation of the Caspase family, PARP cleavage, and modulation of pro- and anti-apoptotic protein levels. Hellebrigenin also induces DNA double-strand breaks, thereby activating the ATM pathway. This compound is primarily utilized in cancer research, particularly in the study of oral squamous cell carcinoma, liver cancer, and other malignancies, due to its capacity to inhibit tumor cell proliferation and clonogenicity.

α-Santalol, a naturally occurring sesquiterpene, functions as an apoptosis inducer through the activation of caspase-3, leading to enhanced apoptotic processes. This compound has demonstrated the ability to reduce cell viability, induce PARP cleavage, and trigger apoptosis in human prostate cancer cells. Additionally, α-Santalol inhibits the Akt/Survivin signaling pathway to promote cellular death. This reagent is valuable for research focused on prostate cancer and diabetes mellitus.

Polyporenic acid C is a lanostane-type triterpenoid that functions as an apoptosis inducer. Isolated from Poria cocos, this compound activates key apoptotic pathways by cleaving caspase-8, caspase-3, and PARP, while modulating the phosphorylation status of Akt, PTEN, and p53. Additionally, Polyporenic acid C enhances JNK activation and exhibits significant anticancer activity against non-small cell lung cancer. This makes it a valuable reagent for research into cancer therapies and apoptotic mechanisms.

3-O-Methylgallic acid, a potent apoptosis inducer, is an anthocyanin metabolite known for its significant antioxidant properties. It effectively inhibits the proliferation of Caco-2 cells with an IC50 value of 24.1 μM, demonstrating its potential in cancer research. This compound is valuable for studying apoptotic pathways and therapeutic strategies in oncology.

Glaucocalyxin A is an ent-kauranoid diterpene derived from Rabdosia japonica var. This compound acts as an apoptosis inducer by inhibiting the nuclear translocation of Five-zinc finger Glis 1 (GLI1), effectively modulating the PI3K/Akt signaling pathway. Its notable antitumor properties make Glaucocalyxin A a valuable reagent for research in cancer biology, particularly in studies focused on osteosarcoma.

Polygalacin D3 is a triterpenoid saponin extracted from the roots of the balloon flower and acts as an apoptosis inducer. It demonstrates significant biological activity by inhibiting the proliferation of non-small cell lung cancer (NSCLC) cell lines through the blockade of the PI3K/Akt signaling pathway. Additionally, Polygalacin D3 induces cell cycle arrest and apoptosis, making it a valuable reagent for cancer research applications.

Dehydroxy-oridonin-vinyl ester is a potent apoptosis inducer that targets the PI3K/Akt signaling pathway. This compound demonstrates strong anti-proliferative activity against SU-DHL-6 lymphoma cells, with an IC₅₀ value of 0.12 μM. Dehydroxy-oridonin-vinyl ester selectively induces cell apoptosis while not interfering with cell cycle progression, making it a valuable tool for research in cancer therapy, particularly in the study of lymphoma.

BIBU1361 dihydrochloride is an apoptosis inducer that primarily targets pro-survival pathways, including Akt/mTOR and gp130/JAK/STAT3. This compound effectively promotes apoptosis while inhibiting autophagy, leading to a reduction in pro-inflammatory cytokine levels, particularly IL-6. BIBU1361 dihydrochloride is valuable for research applications focused on cancer therapy and the modulation of inflammatory responses.

DCZ3301 is a potent apoptosis inducer that functions as an aryl-guanidino inhibitor. It effectively inhibits cell proliferation, induces G2/M cell cycle arrest, and facilitates apoptosis. By downregulating PI3K protein expression and inhibiting AKT phosphorylation, DCZ3301 targets the PI3K/AKT signaling pathway, making it a valuable reagent for cancer research.

Licoricidin (LCD) is a potent apoptosis inducer derived from Glycyrrhiza uralensis Fisch, demonstrating significant anti-cancer properties. It effectively inhibits SW480 colorectal cancer cells with an IC50 of 7.2 μM by promoting cell cycle arrest, apoptosis, and autophagy, making it a promising candidate for chemoprevention and chemotherapy. Additionally, Licoricidin suppresses lung metastasis through the inhibition of tumor angiogenesis and lymphangiogenesis, while improving the tumor microenvironment. In osteosarcoma models, Licoricidin enhances the cytotoxic effects of gemcitabine by inactivating the Akt and NF-κB signaling pathways. Furthermore, Licoricidin alleviates UVA-induced photoaging by scavenging reactive oxygen species and inhibiting MMP-1 activity, indicating its potential in topical anti-aging formulations.

Autophagy Inducer 7 is an effective modulator of autophagy and apoptosis, primarily targeting the Akt/mTOR signaling pathway. This compound promotes autophagy by inhibiting pathway activity and downregulating associated proteins, leading to a reduction in DNA synthesis and inducing G0-G1 cell cycle arrest. Additionally, Autophagy Inducer 7 has demonstrated the ability to inhibit tumor cell proliferation, making it a valuable tool for research in cancer biology and therapeutic strategies involving autophagy.

Crebanine is an isoquinoline-like alkaloid that acts as an apoptosis inducer through antagonism of the α7-nAChR, exhibiting an IC50 value of 19.1 μM. This compound suppresses cancer cell proliferation, migration, and invasion while triggering a reactive oxygen species (ROS) burst that promotes apoptosis. Additionally, Crebanine modulates critical signaling pathways including AKT/FoxO3a, NF-κB, and MAPK, and demonstrates antioxidant properties in microglia by reducing ROS and lipid peroxidation. With applications in studying hepatocellular carcinoma, cerebral ischemia, and Alzheimer's disease, Crebanine may also ameliorate cognitive deficits and ischemia-reperfusion brain damage in rodent models.

Alphitolic acid, an apoptosis inducer, is a triterpene isolated from Quercus aliena. It functions by inhibiting Akt–NF-κB signaling pathways, promoting apoptosis and autophagy. Additionally, Alphitolic acid exhibits anti-inflammatory properties by down-regulating nitric oxide and TNF-α production. This compound is applicable in cancer and inflammation research.

Tributyrin, a triglyceride variant of butyric acid, functions as a stable proagent that induces apoptosis. Upon diffusion through biological membranes, it is metabolized by intracellular lipases to release butyrate, which exerts significant antiproliferative and pro-apoptotic effects within cells. This compound serves as a valuable reagent for research into cell differentiation and apoptosis pathways.