Apoptosis

Avitinib (Abivertinib) maleate is a third-generation, irreversible, and orally active selective EGFR inhibitor with IC50 values of 0.18 nM for both EGFR^L858R and EGFR^T790M, and 7.68 nM for wild-type EGFR. In addition to its EGFR-targeting activity, Avitinib maleate also inhibits BTK phosphorylation and induces apoptosis in mantle cell lymphoma models, demonstrating broad-spectrum anticancer efficacy.

Cearoin is a bioactive compound that promotes both autophagy and apoptosis by inducing reactive oxygen species (ROS) production and activating the ERK signaling pathway. Through this dual mechanism, cearoin contributes to the regulation of cellular stress responses and programmed cell death. Its ability to modulate these processes makes it a valuable candidate for research in cancer biology and other diseases involving dysregulated autophagy or apoptosis.

Penehyclidine hydrochloride (also known as Penequinine hydrochloride) is a selective anticholinergic agent that acts as an antagonist of muscarinic M1 and M3 receptors. It exerts anti-inflammatory effects by modulating immune signaling in lung tissue, notably through activation of the NF-κB pathway and inhibition of pro-inflammatory cytokine release. In preclinical studies, Penehyclidine hydrochloride has been shown to alleviate pulmonary inflammation in rat models of chronic obstructive pulmonary disease (COPD), particularly under conditions of mechanical ventilation. These properties suggest its potential utility in managing respiratory inflammatory conditions and improving outcomes in mechanically ventilated patients with COPD.

MY-673 is a colchicine binding site inhibitor (CBSI) that disrupts microtubule dynamics by inhibiting tubulin polymerization. In addition to its antimitotic effects, MY-673 suppresses the ERK signaling pathway, which leads to modulation of SMAD4 protein expression within the TGF-β/SMAD signaling axis. These combined actions result in potent inhibition of cancer cell proliferation and migration, and the induction of apoptosis, both in vitro and in vivo. MY-673 holds promise as a therapeutic candidate for targeting cancers driven by aberrant microtubule dynamics and dysregulated TGF-β/ERK signaling.

Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue that exhibits potent anti-inflammatory activity. It exerts its effects by blocking mitogen-activated protein kinase (MAPK) signaling and inhibiting the nuclear translocation of the NF-κB subunit p65, thereby suppressing key inflammatory pathways. Additionally, compound 5a27 reduces neutrophil infiltration and the production of pro-inflammatory cytokines. In vivo, it significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI), highlighting its potential as a therapeutic candidate for inflammatory and respiratory disorders.

Gamma-linolenic acid (γ-linolenic acid, GLA) is an orally active omega-6 unsaturated fatty acid with broad pharmacological activities. It exhibits anti-inflammatory effects by inhibiting the NF-κB signaling pathway and suppressing the phosphorylation of ERK1/2 and JNK, key mediators of inflammatory responses. GLA also induces apoptosis in cancer cells, contributing to its anticancer potential. Additionally, it possesses antioxidant properties and has been shown to improve memory function, suggesting neuroprotective benefits. These multifunctional effects position gamma-linolenic acid as a promising compound for research in inflammation, oncology, and neurological disorders.

Lysophosphatidylcholines (LPCs) are orally active lysolipids and key components of oxidized low-density lipoprotein (oxLDL). They are bioactive molecules known to induce cellular injury, promote the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), and trigger apoptosis. LPCs play a significant role in the pathophysiology of various inflammatory conditions and have been implicated in the progression of sepsis by amplifying inflammatory responses. Due to these properties, LPCs are actively studied in the context of inflammation, cardiovascular disease, and sepsis-related research.

AS1411 (AGRO-100) is a G-rich oligonucleotide aptamer that selectively targets nucleolin, a nucleoprotein overexpressed on the surface and within the nucleus of many cancer cells. It inhibits tumor cell proliferation by disrupting nucleolin-containing complexes, thereby affecting key oncogenic processes. AS1411 has been shown to reduce PRMT5 expression and inhibit tumor growth in DU145 prostate cancer cells, and to block the interaction between nucleolin and *bcl-2* mRNA in MCF-7 breast cancer cells, leading to decreased Bcl-2 protein levels and enhanced apoptosis. Beyond its intrinsic anticancer activity, AS1411 serves as a precision-targeting carrier for the delivery of nanoparticles, oligonucleotides, and small molecules to cancer cells. AS1411-conjugated gold nanospheres have demonstrated effective inhibition of breast cancer cell proliferation in vitro and in vivo, with the added advantage of crossing the blood-brain barrier and exhibiting low tissue toxicity, making AS1411 a versatile platform for targeted cancer therapy and drug delivery.

Rhamnetin is a naturally occurring flavonoid and quercetin derivative found in *Coriandrum sativum*. It functions as an inhibitor of secretory phospholipase A₂ and histone deacetylase 2 (HDAC2), contributing to its broad pharmacological profile. Rhamnetin exhibits notable antitumor, antioxidant, and anti-inflammatory activities, making it a promising compound for research in cancer, oxidative stress-related conditions, and inflammatory diseases.

Triacetin (Glyceryl triacetate) is an orally active synthetic triester of glycerol and acetic acid that serves as a bioavailable source of acetate. It freely crosses the blood–brain barrier and cellular membranes, making it particularly effective in targeting central nervous system malignancies. In glioma cells, Triacetin increases intracellular acetate levels, promotes histone acetylation, and induces cell cycle arrest and apoptosis. Additionally, Triacetin enhances the chemotherapeutic efficacy of Temozolomide (TMZ), supporting its potential as an adjuvant in glioma treatment strategies.

Alteminostat (CKD-581) is a potent, broad-spectrum histone deacetylase (HDAC) inhibitor that targets both class I and class II HDAC isoforms. It promotes histone H3 and α-tubulin acetylation, indicating effective inhibition of nuclear and cytoplasmic HDAC activity. Alteminostat is being investigated for its therapeutic potential in hematologic malignancies, including lymphoma and multiple myeloma, and serves as a valuable tool in epigenetic cancer research.

MC1742 is a potent pan-HDAC inhibitor with broad activity across multiple HDAC isoforms, exhibiting IC₅₀ values of 0.1 μM (HDAC1), 0.11 μM (HDAC2), 0.02 μM (HDAC3), 0.007 μM (HDAC6), 0.61 μM (HDAC8), 0.04 μM (HDAC10), and 0.1 μM (HDAC11). It effectively increases acetylation of histone H3 and α-tubulin, markers of HDAC inhibition. MC1742 inhibits the growth of cancer stem cells (CSCs), and induces growth arrest, apoptosis, and differentiation, particularly in sarcoma CSC models, making it a promising candidate for targeting therapy-resistant cancer cell populations.

SelSA is a selective and orally active histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 56.9 nM. It also inhibits ERK1/2 phosphorylation, contributing to its anticancer effects. SelSA suppresses the proliferation of breast cancer and hepatocellular carcinoma cells with IC₅₀ values ranging from 0.58 to 2.6 μM, inhibits migration and invasion of Huh7 cells, and induces apoptosis. In vivo, SelSA demonstrates significant antitumor activity, supporting its potential as a therapeutic agent for solid tumors.

KH16 is a potent histone deacetylase (HDAC) inhibitor with low nanomolar activity, selectively targeting class I HDACs—HDAC1, HDAC2, and HDAC3—with IC₅₀ values ranging from 6 to 34 nM. It effectively induces apoptosis and exhibits broad-spectrum antitumor activity across cancer cells with diverse gene expression profiles, making it a promising candidate for epigenetic cancer therapy research.

1,6,7-Trihydroxyxanthone is a potent anticancer compound that inhibits tumor cell proliferation and induces apoptosis. It downregulates the expression of Bmi-1, a known oncogenic regulator, while upregulating the protein levels of tumor suppressors p14 and p16. These effects highlight its potential as a therapeutic agent for targeting oncogenic pathways in cancer research.

AG-825 is a selective, ATP-competitive inhibitor of ErbB2 (HER2) tyrosine kinase, with an IC₅₀ of 0.35 μM. It exhibits both anticancer and anti-inflammatory activities and has been shown to significantly accelerate apoptosis in human neutrophils. AG-825 also increases β₁-adrenergic receptor (β₁AR) density, suggesting potential cardiomodulatory effects. Due to its multifaceted biological activity, AG-825 is a valuable compound for research in oncology, inflammation, and cardiovascular disease.

Licochalcone D is a naturally occurring flavonoid primarily found in the root of *Glycyrrhiza uralensis* (Chinese licorice). It functions as a potent and orally active inhibitor of the NF-κB p65 subunit, a key regulator of inflammation and cancer-related signaling pathways. Licochalcone D exhibits broad pharmacological properties, including antioxidant, anti-inflammatory, and anticancer activities, making it a promising candidate for research in inflammation-related diseases and oncology.

AES-350 is a potent and orally bioavailable histone deacetylase 6 (HDAC6) inhibitor, with an IC₅₀ of 0.0244 μM and a Kᵢ of 0.035 μM. It also exhibits inhibitory activity against HDAC3 and HDAC8, with IC₅₀ values of 0.187 μM and 0.245 μM, respectively. AES-350 induces apoptosis in acute myeloid leukemia (AML) cells through HDAC inhibition, making it a promising compound for AML research and the development of epigenetic-based cancer therapies.

GEM144 is a potent and orally bioavailable dual inhibitor of DNA polymerase α (POLA1) and histone deacetylase 11 (HDAC11). It promotes p53 acetylation, induces p21 activation, and triggers G1/S cell cycle arrest followed by apoptosis. GEM144 exhibits significant antitumor efficacy in human orthotopic malignant pleural mesothelioma xenograft models, highlighting its potential as a targeted therapeutic agent for aggressive thoracic malignancies.

MIR002 is a potent, orally bioavailable dual inhibitor targeting DNA polymerase α (POLA1) and histone deacetylase 11 (HDAC11). It induces p53 acetylation, upregulates p21 expression, and triggers G1/S cell cycle arrest followed by apoptosis. MIR002 demonstrates significant antitumor efficacy in vivo, highlighting its potential as a therapeutic agent for cancers driven by POLA1 and HDAC11 dysregulation.

HS-276 is an orally bioavailable, potent, and highly selective inhibitor of transforming growth factor-β–activated kinase 1 (TAK1), with a Kᵢ of 2.5 nM. It exhibits strong inhibition of TAK1 and moderate activity against a panel of other kinases, including CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with respective IC₅₀ values ranging from 8.25 to 5585 nM. HS-276 is a valuable tool for investigating TAK1-mediated signaling pathways and holds therapeutic potential for inflammatory conditions such as rheumatoid arthritis (RA).

BTX-A51 (Casein Kinase Inhibitor A51) is a potent, orally bioavailable inhibitor of casein kinase 1α (CK1α). It effectively induces apoptosis in leukemia cells and demonstrates strong anti-leukemic activity in preclinical models, making it a promising therapeutic candidate for hematologic malignancies.

F5446 (Compound 1) is a selective small-molecule inhibitor of the histone methyltransferase SUV39H1. By reducing H3K9 trimethylation (H3K9me3) at the Fas promoter, F5446 upregulates Fas expression and enhances the sensitivity of colorectal carcinoma cells to Fas ligand (FasL)-induced apoptosis in vitro. In vivo, F5446 effectively suppresses the growth of human colorectal tumor xenografts, highlighting its potential as an epigenetic therapeutic agent in cancer treatment.

AR420626 is a selective agonist of free fatty acid receptor 3 (FFAR3, also known as GPR41), with an IC₅₀ of 117 nM. It demonstrates anti-inflammatory, antitumor, and antidiabetic activities. AR420626 improves neurogenic diarrhea by modulating neural pathways mediated by nicotinic acetylcholine receptors (nAChRs). In cancer models, it suppresses the growth of HepG2 xenografts and inhibits hepatoma cell proliferation through apoptosis induction. Additionally, AR420626 mitigates allergic asthma and eczema and enhances glucose uptake by activating FFAR3-mediated Ca²⁺ signaling, offering potential therapeutic benefits in metabolic disorders such as diabetes.

ReACp53 is a cell-penetrating peptide that inhibits p53 amyloid aggregation, restoring p53 function in cancer cell lines and organoids derived from high-grade serous ovarian carcinoma (HGSOC).

PROTAC RIPK Degrader-2 is a non-peptidic, VHL-based PROTAC that selectively targets the serine/threonine kinase RIPK2 for degradation. It promotes cancer cell death and ion channel activation, while also inhibiting key protein interactions involved in disease pathways, including those related to cancer and diabetes.

HXR9 is a cell-permeable peptide that functions as a competitive antagonist of the HOX/PBX interaction, disrupting the binding of HOX proteins (paralogues 1–8) to the transcription factor PBX. It selectively inhibits proliferation and induces apoptosis in cells with elevated HOXA/PBX3 expression, such as MLL-rearranged leukemic cells, making it a valuable tool for studying HOX/PBX-driven oncogenesis.

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.

ASK1-IN-11 is a potent inhibitor of apoptosis signal-regulating kinase 1 (ASK1), exhibiting an IC50 of less than 200 nM. This compound also demonstrates inhibitory effects on TNF-α, MYLK/MLCK kinases, and hERG potassium channels. The primary research applications of ASK1-IN-11 include investigations into inflammation-related pathways.

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.

R1-ICR-5 is a selective RIPK1 PROTAC degrader designed to mediate protein degradation via the VHL pathway. This compound promotes the degradation of RIPK1, subsequently dysregulating TNFR1 and TLR3/4 signaling pathways, enhancing the activity of NF-κB, MAPK, and IFN signaling. Additionally, R1-ICR-5 facilitates RIPK3 activation, leading to necroptosis. This reagent is applicable in research focused on triple-negative breast cancer and skin inflammation.

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.

6-Dehydrogingerdione serves as an apoptosis inducer by enhancing the sensitivity of human hepatoblastoma Hep G2 cells to TRAIL-induced cell death. This compound mediates its effects through the production of reactive oxygen species, which lead to an upregulation of death receptor 5 (DR5). Its ability to modulate apoptotic pathways makes it a valuable tool for research in cancer therapies and cell death mechanisms.

3-O-Acetyloleanolic acid (3AOA) is an oleanolic acid derivative that functions as an apoptosis inducer. It has demonstrated significant anti-cancer properties, promoting cell death in various cancer types, and displays anti-angiogenic activity, inhibiting the formation of new blood vessels. Research applications include studies on cancer therapy and the mechanisms of apoptosis and angiogenesis.

Desacetylcinobufotalin is a natural compound known for its role as an apoptosis inducer. It exhibits significant inhibitory effects on HepG2 cancer cells, with an IC50 value demonstrating potent cytotoxicity. This compound is primarily used in cancer research to explore mechanisms of programmed cell death and therapeutic strategies for hepatic carcinoma.

DPBQ is a potent p53 activator that promotes apoptosis specifically in polyploid cells. It induces the expression and phosphorylation of p53 without inhibiting topoisomerase or directly binding to DNA. This selective action makes DPBQ a valuable tool for research involving polyploidy and the modulation of p53 signaling pathways.

BMS 310705 (21-Aminoepothilone B) is an apoptosis inducer that targets malignancies, including ovarian, renal, bladder, and lung carcinoma. This compound promotes significant apoptotic activity through a mitochondrial-mediated pathway, making it a valuable tool for cancer research. Its effectiveness in inducing programmed cell death highlights its potential applications in studying tumor biology and developing novel therapeutic strategies.

(S)-(-)-Perillic acid is a terpenoid compound known for its role as an apoptosis inducer. It promotes cell apoptosis and cell cycle arrest while enhancing the levels of key proteins such as Bax, Bcl-2, p21, and caspase-3. This reagent is suitable for research applications related to cancer and infectious diseases, providing valuable insights into therapeutic mechanisms and cellular pathways.

Toddaculin is a natural coumarin known for its role as an apoptosis inducer. It effectively induces differentiation and apoptotic processes in leukemic cells while simultaneously suppressing excessive osteoclast activity. Additionally, Toddaculin promotes osteoblast differentiation and mineralization and demonstrates anti-inflammatory properties, making it a valuable reagent for research in cancer biology and bone metabolism.

STIMA-1 is a p53 activator that stimulates mutant p53 DNA binding in vitro. This compound induces the expression of p53 target proteins and promotes apoptosis in human tumor cells expressing mutant p53. It serves as a valuable tool for researching p53-driven pathways and potential therapeutic strategies for cancers associated with p53 mutations.

2,3-DCPE hydrochloride is an apoptosis inducer that promotes programmed cell death through the downregulation of Bcl-XL expression. This reagent exhibits anti-tumor activity, making it a valuable tool in cancer research, particularly in studies focused on cell survival mechanisms and therapeutic targets for malignancies.

(-)-Epipodophyllotoxin is an apoptosis inducer derived from the American mayapple, Podophyllum peltatum. Exhibiting potent antiproliferative activity, it demonstrates GI50 values of 0.36 and 0.24 μM against HeLa and MCF-7 cancer cell lines, respectively. Additionally, (-)-Epipodophyllotoxin has been shown to inhibit mitotic spindle assembly in vitro, making it a valuable reagent for cancer research and studies involving cell cycle dynamics.

3-Dehydrotrametenolic acid is an apoptosis inducer that functions as a lactate dehydrogenase (LDH) inhibitor. Isolated from the sclerotium of Poria cocos, it has been shown to promote adipocyte differentiation in vitro and to enhance insulin sensitivity in vivo. Additionally, 3-dehydrotrametenolic acid exhibits anticancer properties by inducing apoptosis in cancer cells, making it a valuable compound for research in cancer biology and metabolic disorders.