As one of the cellular death mechanisms, apoptosis, also known as programmed cell death, can be defined as the process of a proper death of any cell under certain or necessary conditions. Apoptosis is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body.
Many biochemical events and a series of morphological changes occur at the early stage and increasingly continue till the end of apoptosis process. Morphological event cascade including cytoplasmic filament aggregation, nuclear condensation, cellular fragmentation, and plasma membrane blebbing finally results in the formation of apoptotic bodies. Several biochemical changes such as protein modifications/degradations, DNA and chromatin deteriorations, and synthesis of cell surface markers form morphological process during apoptosis.
Apoptosis can be stimulated by two different pathways: (1) intrinsic pathway (or mitochondria pathway) that mainly occurs via release of cytochrome c from the mitochondria and (2) extrinsic pathway when Fas death receptor is activated by a signal coming from the outside of the cell.
Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis.
Caspase family comprises conserved cysteine aspartic-specific proteases, and members of caspase family are considerably crucial in the regulation of apoptosis. There are 14 different caspases in mammals, and they are basically classified as the initiators including caspase-2, -8, -9, and -10; and the effectors including caspase-3, -6, -7, and -14; and also the cytokine activators including caspase-1, -4, -5, -11, -12, and -13. In vertebrates, caspase-dependent apoptosis occurs through two main interconnected pathways which are intrinsic and extrinsic pathways. The intrinsic or mitochondrial apoptosis pathway can be activated through various cellular stresses that lead to cytochrome c release from the mitochondria and the formation of the apoptosome, comprised of APAF1, cytochrome c, ATP, and caspase-9, resulting in the activation of caspase-9. Active caspase-9 then initiates apoptosis by cleaving and thereby activating executioner caspases. The extrinsic apoptosis pathway is activated through the binding of a ligand to a death receptor, which in turn leads, with the help of the adapter proteins (FADD/TRADD), to recruitment, dimerization, and activation of caspase-8 (or 10). Active caspase-8 (or 10) then either initiates apoptosis directly by cleaving and thereby activating executioner caspase (-3, -6, -7), or activates the intrinsic apoptotic pathway through cleavage of BID to induce efficient cell death. In a heat shock-induced death, caspase-2 induces apoptosis via cleavage of Bid.
Bcl-2 family members are divided into three subfamilies including (i) pro-survival subfamily members (Bcl-2, Bcl-xl, Bcl-W, MCL1, and BFL1/A1), (ii) BH3-only subfamily members (Bad, Bim, Noxa, and Puma9), and (iii) pro-apoptotic mediator subfamily members (Bax and Bak). Following activation of the intrinsic pathway by cellular stress, pro‑apoptotic BCL‑2 homology 3 (BH3)‑only proteins inhibit the anti‑apoptotic proteins Bcl‑2, Bcl-xl, Bcl‑W and MCL1. The subsequent activation and oligomerization of the Bak and Bax result in mitochondrial outer membrane permeabilization (MOMP). This results in the release of cytochrome c and SMAC from the mitochondria. Cytochrome c forms a complex with caspase-9 and APAF1, which leads to the activation of caspase-9. Caspase-9 then activates caspase-3 and caspase-7, resulting in cell death. Inhibition of this process by anti‑apoptotic Bcl‑2 proteins occurs via sequestration of pro‑apoptotic proteins through binding to their BH3 motifs.
One of the most important ways of triggering apoptosis is mediated through death receptors (DRs), which are classified in TNF superfamily. There exist six DRs: DR1 (also called TNFR1); DR2 (also called Fas); DR3, to which VEGI binds; DR4 and DR5, to which TRAIL binds; and DR6, no ligand has yet been identified that binds to DR6. The induction of apoptosis by TNF ligands is initiated by binding to their specific DRs, such as TNFα/TNFR1, FasL /Fas (CD95, DR2), TRAIL (Apo2L)/DR4 (TRAIL-R1) or DR5 (TRAIL-R2). When TNF-α binds to TNFR1, it recruits a protein called TNFR-associated death domain (TRADD) through its death domain (DD). TRADD then recruits a protein called Fas-associated protein with death domain (FADD), which then sequentially activates caspase-8 and caspase-3, and thus apoptosis. Alternatively, TNF-α can activate mitochondria to sequentially release ROS, cytochrome c, and Bax, leading to activation of caspase-9 and caspase-3 and thus apoptosis. Some of the miRNAs can inhibit apoptosis by targeting the death-receptor pathway including miR-21, miR-24, and miR-200c.
p53 has the ability to activate intrinsic and extrinsic pathways of apoptosis by inducing transcription of several proteins like Puma, Bid, Bax, TRAIL-R2, and CD95.
Some inhibitors of apoptosis proteins (IAPs) can inhibit apoptosis indirectly (such as cIAP1/BIRC2, cIAP2/BIRC3) or inhibit caspase directly, such as XIAP/BIRC4 (inhibits caspase-3, -7, -9), and Bruce/BIRC6 (inhibits caspase-3, -6, -7, -8, -9).
Any alterations or abnormalities occurring in apoptotic processes contribute to development of human diseases and malignancies especially cancer.
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3.Ashkenazi A, Fairbrother W J, Leverson J D, et al. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors[J]. Nature Reviews Drug Discovery, 2017.
4.McIlwain D R, Berger T, Mak T W. Caspase functions in cell death and disease[J]. Cold Spring Harbor perspectives in biology, 2013, 5(4): a008656.
5.Ola M S, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis[J]. Molecular and cellular biochemistry, 2011, 351(1-2): 41-58.
What is Apoptosis? The Apoptotic Pathways and the Caspase Cascade
Products for Apoptosis
- Apoptosis Inducers(18)
- Bcl-2 Family(71)
- Thymidylate Synthase(8)
- Other Apoptosis(654)
- PD-1/PD-L1 interaction(47)
- RIP kinase(42)
- Cat.No. Product Name Information
- GC26092 Z-LEHD-FMK TFA Z-LEHD-FMK TFA (Caspase-9 Inhibitor) is a cell-permeable, competitive and irreversible inhibitor of enzyme caspase-9, which helps in cell survival.
- GC25743 PIM447 (LGH447) PIM447 (LGH447) is a novel pan-PIM kinase inhibitor with Ki values of 6 pM, 18 pM, 9 pM for PIM1, PIM2, PIM3 respectively. It also inhibits GSK3β, PKN1, and PKCτ, but at a significantly lower potency with IC50 between 1 and 5 μM (>105-fold differential relative to the Ki on PIMs). PIM447 induces apoptosis.
- GC25691 OTS514 hydrochloride OTS514 is a highly potent TOPK(T-LAK cell-originated protein kinase) inhibitor with an IC50 value of 2.6 nM. OTS514 induces cell cycle arrest and apoptosis.
- GC25673 Obatoclax (GX15-070)
- GC25428 Foscenvivint (ICG-001) Foscenvivint (ICG-001) antagonizes Wnt/β-catenin/TCF-mediated transcription and specifically binds to CREB-binding protein (CBP) with IC50 of 3 μM, but is not the related transcriptional coactivator p300. ICG-001 induces apoptosis.
- GC25351 Dimethyl itaconate Dimethyl itaconate can reprogram neurotoxic to neuroprotective primary astrocytes through the regulation of LPS-induced Nod-like receptor protein 3 (NLRP3) inflammasome and nuclear factor 2/heme oxygenase-1 (NRF2/HO-1) pathways.
- GC25160 BMS-1001 BMS-1001 is a potent inhibitor of PD-1/PD-L1 interaction with EC50 of 253 nM. BMS-1001 alleviates the inhibitory effect of the soluble PD-L1 on the T-cell receptor-mediated activation of T-lymphocytes.
- GC68470 SPD304 dihydrochloride
- GC68452 2,4,6-Triiodophenol
- GC68404 Human PD-L1 inhibitor IV
- GC68388 XIAP degrader-1
- GC68385 TNF-α-IN-6
- GC68371 Mutant p53 modulator-1
- GC68369 Belantamab
- GC68308 Bisdemethoxycurcumin-d8
- GC68306 Deoxynyboquinone
- GC68305 Dacetuzumab
- GC68288 Brentuximab
- GC68231 4-Methylsalicylic acid
- GC68213 MitoBloCK-6
- GC68051 Citric acid-d4
- GC68043 2-tert-Butyl-1,4-benzoquinone
- GC68019 NPB
- GC68012 BCL6-IN-7
- GC67969 RIP1/RIP3/MLKL activator 1
- GC67966 Methylstat
- GC67936 Lupiwighteone
- GC67792 NSC49652
- GC67765 p53 Activator 5
- GC67694 PD-1/PD-L1-IN-9 hydrochloride
- GC67680 BIO8898
- GC52516 Erbstatin A tyrosine kinase inhibitor
- GC52489 Ceramide (hydroxy) (bovine spinal cord) A sphingolipid
- GC52486 Ceramide Phosphoethanolamine (bovine) A sphingolipid
- GC52485 Ceramide (non-hydroxy) (bovine spinal cord) A sphingolipid
- GC52476 Bax Inhibitor Peptide V5 (trifluoroacetate salt) A Bax inhibitor
- GC52472 Inostamycin A (sodium salt) A bacterial metabolite with anticancer activity
- GC52469 CL2A-SN-38 (dichloroacetic acid salt) An antibody-drug conjugate containing SN-38
- GC52467 Cell Death Screening Library For screening a variety of cell death pathways
- GC52455 Pixantrone-d8 (maleate) An internal standard for the quantification of pixantrone
- GC52372 Ac-VDVAD-AFC (trifluoroacetate salt) A fluorogenic substrate for caspase-2
- GC52371 Vimentin (G146R) (139-159)-biotin Peptide A biotinylated mutant vimentin peptide
- GC52370 Citrullinated Vimentin (R144) (139-159)-biotin Peptide A biotinylated and citrullinated vimentin peptide
- GC52367 Citrullinated Vimentin (G146R) (R144 + R146) (139-159)-biotin Peptide A biotinylated and citrullinated mutant vimentin peptide
- GC52364 Vimentin (139-159)-biotin Peptide A biotinylated vimentin peptide
- GC52358 Malachite Green (chloride) A triphenylmethane dye
- GC52355 BimS BH3 (51-76) (human) (trifluoroacetate salt) A Bim-derived peptide
- GC52344 Bak BH3 (72-87) (human) (trifluoroacetate salt) A Bak-derived peptide
- GC52325 MeTC7 A vitamin D receptor antagonist
- GC52318 Oleic Acid-13C5 An internal standard for the quantification of oleic acid
- GC52293 STAT3 Inhibitor 4m A STAT3 inhibitor
- GC52291 KAS 08 A STING activator
- GC52288 Fumonisin B1-13C34 An internal standard for the quantification of fumonisin B1
- GC52269 Cinnabarinic Acid-d4 An internal standard for the quantification of cinnabarinic acid
- GC52250 Mevalonate (lithium salt) An intermediate in the mevalonate pathway
- GC52245 CAY10792 An anticancer agent
- GC52227 5-(3',4'-Dihydroxyphenyl)-γ-Valerolactone An active metabolite of various polyphenols
- GC67618 α-Tocopherol phosphate disodium α-Tocopherol phosphate (alpha-Tocopherol phosphate) disodium, a promising antioxidant, can protect against long-wave UVA1 induced cell death and scavenge UVA1 induced ROS in a skin cell model. α-Tocopherol phosphate disodium possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of endothelial progenitor cells under high-glucose/hypoxic conditions and promotes angiogenesis.
- GC67272 N6-Benzyladenosine N6-Benzyladenosine is an adenosine receptor agonist, has a cytoactive activity. N6-Benzyladenosine arrests cell cycle at G0/G1 phase and induces cell apoptosis. N6-Benzyladenosine also exerts inhibitory effect on T. gondii adenosine kinase and glioma-.
- GC66824 D-α-Tocopherol Succinate D-α-Tocopherol Succinate (Vitamin E succinate) is an antioxidant tocopherol and a salt form of vitamin E. D-α-Tocopherol Succinate inhibits Cisplatin -induced cytotoxicity. D-α-Tocopherol Succinate can be used for the research of cancer.
- GC66479 GSK2593074A GSK2593074A (GSK'074) is a necroptosis inhibitor with dual targeting ability to both RIP1 and RIP3.
- GC66462 MGH-CP1 MGH-CP1 is a potent and orally active TEAD2 and TEAD4 auto-palmitoylation inhibitor with IC50s of 710 nM and 672 nM, respectively. MGH-CP1 can decrease the palmitoylation levels of endogenous or ectopically expressed TEAD proteins in cells. MGH-CP1 can suppress Myc expression, inhibit epithelial over-proliferation, and induce apoptosis when together with Lats1/2 deletion.
- GC66460 UCB-5307 UCB-5307 is a potent TNF signaling inhibitor with a KD of 9 nM for human TNFα. UCB-5307 can penetrate the preformed hTNF/hTNFR1 complex.
- GC66403 Z-DEVD-AMC Z-DEVD-AMC is a selective caspase-3 substrate that can be measured by fluorescence spectrometry. AMC can be used as a fluorescence reference standard for AMC-based enzyme substrates including AMC-based caspase substrates.
- GC66394 Penpulimab Penpulimab is an IgG1 backbone anti-PD-1 monoclonal antibody with antitumor activities.
- GC66382 Lucatumumab Lucatumumab (HCD122) is a fully human anti-CD40 antagonist monoclonal antibody, which blocks CD40/CD40L-mediated signaling. Lucatumumab efficiently mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and clearance of tumor cells, can be used for refractory lymphomas, CLL and multiple myeloma research.
- GC66378 Serplulimab Serplulimab (HLX 10) is humanized monoclonal anti-PD-1 antibody. Serplulimab can be used in research of small cell lung cancer.
- GC66370 Zapalog Zapalog is a photocleavable small-molecule heterodimerizer that can be used to repeatedly initiate, and instantaneously terminate, a physical interaction between two target proteins. Zapalog dimerizes any two proteins tagged with the FKBP and DHFR domains until exposure to light causes its photolysis.
- GC66356 Cusatuzumab Cusatuzumab is a human αCD70 monoclonal antibody. Cusatuzumab shows cytotoxicity activity with enhanced antibody-dependent cellular. Cusatuzumab reduces leukemia stem cells (LSCs) and triggers gene signatures related to myeloid differentiation and apoptosis. Cusatuzumab has the potential for the research of Acute myeloid leukemia (AML).
- GC66354 Ezetimibe-d4-1 Ezetimibe-d4 is deuterium labeled Ezetimibe. Ezetimibe (SCH 58235) is a potent cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator.
- GC66345 Golimumab Golimumab (CNTO-148) is a potent human IgG1 TNFα antagonist monoclonal antibody. Golimumab has anti-inflammation activitity and inhibits IL-6 and IL-1β production. Golimumab acts via targeting and neutralizing TNF to prevent inflammation and destruction of cartilage and bone. Golimumab has the anticancer activity and induces cell apoptosis. Golimumab can be used for rheumatoid arthritis, Crohn's disease and cancer research.
- GC66344 Envafolimab Envafolimab (ASC 22; KN 035) is a recombinant protein of a humanized single-domain anti- PD-L1 antibody. Envafolimab is created by a fusion of the of anti-PD-L1 domain with Fc fragment of human IgG1 antibody. Envafolimab blocks interaction between PD-L1 and PD-1 with an IC50 value of 5.25nm. Envafolimab shows antitumor activity. Envafolimab has the potential for the research of solid tumors.
- GC66343 n-Butyl-β-D-fructofuranoside n-Butyl-β-D-fructofuranoside could be isolated from kangaisan. n-Butyl-β-D-fructofuranoside induces apoptosis through the mitochondrial pathway. n-Butyl-β-D-fructofuranoside can be used for cancer research.
- GC66337 Anti-Mouse PD-L1 Antibody Anti-Mouse PD-L1 Antibody is an anti-mouse PD-L1 IgG2b antibody inhibitor derived from host Rat.
- GC66054 Nrf2 activator-4 Nrf2 activator-4 (Compound 20a) is a highly potent, orally active Nrf2 activator with an EC50 of 0.63 μM. Nrf2 activator-4 suppresses reactive oxygen species against oxidative stress in microglia. Nrf2 activator-4 effectively recovers the learning and memory impairment in a scopolamine-induced mouse model.
- GC66048 δ-Secretase inhibitor 11 δ-Secretase inhibitor 11 (compound 11) is an orally active, potent, BBB-penetrated, non-toxic, selective and specific δ-secretase inhibitor, with an IC50 of 0.7 μM. δ-Secretase inhibitor 11 interacts with both the active site and allosteric site of δ-secretase. δ-Secretase inhibitor 11 attenuates tau and APP (amyloid precursor protein) cleavage. δ-Secretase inhibitor 11 ameliorates synaptic dysfunction and cognitive impairments in tau P301S and 5XFAD transgenic mouse models. δ-Secretase inhibitor 11 can be used for Alzheimer's disease research.
- GC66021 TP-021 TP-021 (BCL6-IN-8c) is a potent and orally active B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor with an IC50 of 0.10 μM in cell-free enzyme-linked immunosorbent assay.
- GC66017 Mcl-1 inhibitor 6 Mcl-1 inhibitor 6 is an orally active, selective myeloid cell leukemia 1 (Mcl-1) protein inhibitor with a Kd of 0.23 nM and a Ki of 0.02 μM. Mcl-1 inhibitor 6 possesses superior selectivity over other Bcl-2 family members (Bcl-2, Bcl2A1, Bcl-xL, and Bcl-w, Kd>10 μM). Mcl-1 inhibitor 6 is a potent antitumor agent.
- GC66004 K67 K67 specifically inhibits the interaction between Keap1 and S349-phosphorylated p62. K67 prevents p-p62 from blocking the binding of Keap1 and Nrf2. K67 effectively inhibits the proliferation of HCC cultures with high cellular S351-phosphorylated p62 by restoring the ubiquitination and degradation of Nrf2 driven by Keap1.
- GC65967 RIP2 Kinase Inhibitor 3 RIP2 Kinase Inhibitor 3 is a highly potent and selective inhibitor of receptor interacting protein-2 (RIP2) Kinase with an IC50 of 1 nM .
- GC65961 P53R3 P53R3 is a potent p53 reactivator and restores sequence-specific DNA binding of p53 hot spot mutants, including p53R175H, p53R248W and p53R273H. P53R3 induces p53-dependent antiproliferative effects with much higher specificity than PRIMA-1. P53R3 enhances the recruitment of wild-type p53 and p53M237I to several target gene promoters. P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5). P53R3 is used for cancer research.
- GC65920 PD1-PDL1-IN 1 PD1-PDL1-IN 1 is a potent programmed cell death 1 (PD-1) inhibitor. PD1-PDL1-IN 1 is useful as immune modulator.
- GC65880 ADH-6 TFA ADH-6 TFA is a tripyridylamide compound. ADH-6 abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. ADH-6 TFA targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53's transcriptional activity, leading to cell cycle arrest and apoptosis. ADH-6 TFA has the potential for the research of cancer diseases.
- GC52196 RGD Peptide RGD Peptide acts as an inhibitor of integrin-ligand interactions and plays an important role in cell adhesion, migration, growth, and differentiation.
- GC52192 (S)-4'-nitro-Blebbistatin (S)-4'-nitro-Blebbistatin is a non-cytotoxic, photostable, fluorescent and specific Myosin II inhibitor, usd in the study of the specific role of myosin II in physiological, developmental, and cell biological studies.
- GC52191 Deacetylanisomycin Deacetylanisomycin is a potent growth regulator in plants and an inactive derivative of Anisomycin.
- GC52175 IQA
- GC65610 (R)-5-Hydroxy-1,7-diphenyl-3-heptanone (R)-5-Hydroxy-1,7-diphenyl-3-heptanone is a diarylheptanoid that can be found in Alpinia officinarum.
- GC65580 Sugemalimab Sugemalimab is a fully human, full length, anti-programmed death ligand 1 (PD-L1) immunoglobulin G4 (IgG4) monoclonal antibody (mAb). Sugemalimab shows anticancer activities and can be used for non-small cell lung cancer research.
- GC65565 Cyproheptadine Cyproheptadine is a potent and orally active 5-HT2A receptor antagonist, with antidepressant and antiserotonergic effects.
- GC65555 PROTAC FLT-3 degrader 1 PROTAC FLT-3 degrader 1 is a von Hippel-Lindau-based PROTAC FLT-3 internal tandem duplication (ITD) degrader with an IC50 0.6 nM. Anti-proliferative activity; apoptosis induction.
- GC65542 NSC-87877 disodium NSC-87877 disodium is a potent inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (SH-PTP2 and SH-PTP1), with IC50 values of 0.318 μM, 0.355 μM shp2 and shp1, respectively. NSC-87877 also inhibits dual-specificity phosphatase 26 (DUSP26).
Certolizumab pegol (Certolizumab) is a recombinant, polyethylene glycolylated, antigen-binding fragment of a humanized monoclonal antibody that selectively targets and neutralizes tumour necrosis factor-α (TNF-α).
- GC65474 QM31 QM31 (SVT016426), a cytoprotective agent, is a selective inhibitor of Apaf-1. QM31 inhibits the formation of the apoptosome (IC50=7.9μM), the caspase activation complex composed by Apaf-1, cytochrome c, dATP and caspase-9. QM31 exerts mitochondrioprotective functions and interferes with the intra-S-phase DNA damage checkpoint.
- GC65467 RIPK1-IN-10 RIPK1-IN-10 is a potent RIPK1 inhibitor, example 37, extracted from patent WO2021160109.
- GC65460 HDACs/mTOR Inhibitor 1 HDACs/mTOR Inhibitor 1 is a dual Histone Deacetylases (HDACs) and mammalian target of Rapamycin (mTOR) target inhibitor for treating hematologic malignancies, with IC50s of 0.19 nM, 1.8 nM, 1.2 nM and >500 nM for HDAC1, HDAC6, mTOR and PI3Kα, respectively. HDACs/mTOR Inhibitor 1 stimulates cell cycle arrest in G0/G1 phase and induce tumor cell apoptosis with low toxicity in vivo.
- GC65442 Musk ketone Musk ketone (MK) is a widely used artificial fragrance.
- GC65433 Tafasitamab Tafasitamab (XmAb5574) is an Fc-modified, humanized monoclonal antibody that binds to the human B-cell surface antigenCD19.
- GC65428 BLM-IN-1 BLM-IN-1 (compound 29) is an effective Bloom syndrome protein (BLM) inhibitor, with a strong BLM binding KD of 1.81 μM and an IC50 of 0.95 μM for BLM. Induces DNA damage response, as well as apoptosis and proliferation arrest in cancer cells.
- GC65395 T025 T025 is an orally active and highly potent inhibitor of Cdc2-like kinase (CLKs), with Kd values of 4.8, 0.096, 6.5, 0.61, 0.074, 1.5 and 32 nM for CLK1, CLK2, CLK3, CLK4, DYRK1A, DYRK1B and DYRK2, respectively. T025 induces caspase-3/7-mediated cell apoptosis. T025 reduces CLK-dependent phosphorylation. T025 exerts anti-proliferative activities in both hematological and solid cancer cell lines (IC50 values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research.