Home >> Signaling Pathways >> Apoptosis

Apoptosis

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.

References:
1.Yağmur Kiraz, Aysun Adan, Melis Kartal Yandim, et al. Major apoptotic mechanisms and genes involved in apoptosis[J]. Tumor Biology, 2016, 37(7):8471.
2.Aggarwal B B, Gupta S C, Kim J H. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey.[J]. Blood, 2012, 119(3):651.
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

Targets for  Apoptosis

Products for  Apoptosis

  1. Cat.No. Product Name Information
  2. GC17448 AT-406 (SM-406) AT-406 (SM-406) (AT-406) is a potent and orally bioavailable Smac mimetic and an antagonist of IAPs, and it binds to XIAP, cIAP1, and cIAP2 proteins with Ki of 66.4, 1.9, and 5.1 nM, respectively. AT-406 (SM-406)  Chemical Structure
  3. GC15870 AT7519 Multi-CDK inhibitor AT7519  Chemical Structure
  4. GC13998 AT7519 Hydrochloride A Cdk inhibitor AT7519 Hydrochloride  Chemical Structure
  5. GC10638 AT9283 A broad spectrum kinase inhibitor AT9283  Chemical Structure
  6. GC18133 ATB-346 ATB-346 (ATB-346), an orally active non-steroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase-1 and 2 (COX-1 and 2). ATB-346  Chemical Structure
  7. GC32704 Atezolizumab (MPDL3280A) Atezolizumab (MPDL3280A) (MPDL3280A) is a selective humanized monoclonal IgG1 antibody against programmed death ligand 1 (PD-L1), used for cancer research. Atezolizumab (MPDL3280A)  Chemical Structure
  8. GC62499 ATH686 ATH686 is a potent, selective and ATP-competitive FLT3 inhibitor. ATH686 target mutant FLT3 protein kinase activity and inhibit the proliferation of cells harboring FLT3 mutants via induction of apoptosis and cell cycle inhibition. ATH686 has antileukemic effects. ATH686  Chemical Structure
  9. GC46892 ATRA-BA Hybrid A prodrug form of all-trans retinoic acid and butyric acid ATRA-BA Hybrid  Chemical Structure
  10. GN10394 Atractylenolide III Atractylenolide III  Chemical Structure
  11. GC15878 Atractyloside Dipotassium Salt Inhibitor of ADP/ATP translocases Atractyloside Dipotassium Salt  Chemical Structure
  12. GC39699 Aurintricarboxylic acid Aurintricarboxylic acid is a nanomolar-potency, allosteric antagonist with selectivity towards αβ-methylene-ATP-sensitive P2X1Rs and P2X3Rs, with IC50s of 8.6 nM and 72.9 nM for rP2X1R and rP2X3R, respectively. Aurintricarboxylic acid  Chemical Structure
  13. GC46895 Aurintricarboxylic Acid (ammonium salt) A protein synthesis inhibitor with diverse biological activities Aurintricarboxylic Acid (ammonium salt)  Chemical Structure
  14. GC13332 Aurora A Inhibitor I A potent and selective inhibitor of Aurora A kinase Aurora A Inhibitor I  Chemical Structure
  15. GC15295 AUY922 (NVP-AUY922) An Hsp90 inhibitor AUY922 (NVP-AUY922)  Chemical Structure
  16. GC31719 Avelumab (Anti-Human PD-L1, Human Antibody) Avelumab (Anti-Human PD-L1, Human Antibody) is a fully human IgG1 anti-PD-L1 monoclonal antibody with potential antibody-dependent cell-mediated cytotoxicity. Avelumab (Anti-Human PD-L1, Human Antibody)  Chemical Structure
  17. GC42880 Avenanthramide-C methyl ester Avenanthramide-C methyl ester is an inhibitor of NF-κB activation that acts by blocking the phosphorylation of IKK and IκB (IC50 ~ 40 μM). Avenanthramide-C methyl ester  Chemical Structure
  18. GC35440 AX-024 AX-024 is an orally available, first-in-class inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 ~1 nM. AX-024  Chemical Structure
  19. GC19046 AX-024 hydrochloride AX-024 hydrochloride is an cytokine release inhibitor which can strongly inhibit the production of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), interferon-γ (IFN-γ), IL-10 and IL-17A. AX-024 hydrochloride  Chemical Structure
  20. GC17045 AXL1717 A potent and selective inhibitor of IGF-1R AXL1717  Chemical Structure
  21. GC15055 AZ 628

    Raf kinases,potent and ATP-competitive

    AZ 628  Chemical Structure
  22. GC13433 AZ 960 A JAK2 inhibitor AZ 960  Chemical Structure
  23. GC46901 Azadirachtin A naturally-occurring insecticide Azadirachtin  Chemical Structure
  24. GC15033 Azathioprine purine synthesis and GTP-binding protein Rac1 activation inhibitor Azathioprine  Chemical Structure
  25. GC48971 AZD 1152 (hydrochloride) A prodrug for a potent Aurora B inhibitor AZD 1152 (hydrochloride)  Chemical Structure
  26. GC18566 AZD 3147 A dual mTORC1/mTORC2 inhibitor AZD 3147  Chemical Structure
  27. GC50109 AZD 5582 dihydrochloride Dimeric Smac mimetic; potent IAP inhibitor AZD 5582 dihydrochloride  Chemical Structure
  28. GC33247 AZD-5991 An Mcl-1 inhibitor AZD-5991  Chemical Structure
  29. GC33283 AZD-5991 Racemate AZD-5991 Racemate is the racemate of AZD-5991. AZD-5991 Racemate is a Mcl-1 inhibitor with an IC50 of <3 nM in FRET assay. AZD-5991 Racemate  Chemical Structure
  30. GC33239 AZD-5991 S-enantiomer AZD-5991 S-enantiomer is the less active enantiomer of AZD-5991. AZD-5991 S-enantiomer is a Mcl-1 inhibitor with an IC50 of 6.3 μM in FRET assay and a Kd of 0.98 μM in surface plasmon resonance (SPR) assay. AZD-5991 S-enantiomer  Chemical Structure
  31. GC64938 AZD-7648 AZD-7648 is a potent, orally active, selective DNA-PK inhibitor with an IC50 of 0.6 nM. AZD-7648 induces apoptosis and shows antitumor activity. AZD-7648  Chemical Structure
  32. GC12660 AZD1208 A pan-Pim kinase inhibitor AZD1208  Chemical Structure
  33. GC13029 AZD2014 AZD2014 (AZD2014) is an ATP competitive mTOR inhibitor with an IC50 of 2.81 nM. AZD2014 inhibits both mTORC1 and mTORC2 complexes. AZD2014  Chemical Structure
  34. GC33255 AZD4320 AZD4320 is a novel BH3-mimicking dual BCL2/BCLxL inhibitor with IC50s of 26 nM, 17 nM, and 170 nM for KPUM-MS3, KPUM-UH1, and STR-428 cells, respectively. AZD4320  Chemical Structure
  35. GC19050 AZD5582 AZD5582 is a novel class of dimeric Smac mimetics as potent IAP antagonist; binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP (IC50 = 15, 21, and 15 nM, respectively). AZD5582  Chemical Structure
  36. GC16380 AZD8055 MTOR inhibitor AZD8055  Chemical Structure
  37. GC19054 Azoramide Azoramide is a small-molecule modulator of the unfolded protein response with antidiabetic activity. Azoramide  Chemical Structure
  38. GC46904 Azoxystrobin A broad-spectrum fungicide Azoxystrobin  Chemical Structure
  39. GC60616 AZT triphosphate AZT triphosphate (3'-Azido-3'-deoxythymidine-5'-triphosphate) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate  Chemical Structure
  40. GC60617 AZT triphosphate TEA AZT triphosphate TEA (3'-Azido-3'-deoxythymidine-5'-triphosphate TEA) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate TEA  Chemical Structure
  41. GC35458 Bacopaside II A triterpene glycoside Bacopaside II  Chemical Structure
  42. GC34263 Bak BH3 Bak BH3 is derived from the BH3 domain of Bak, can antagonize the function of Bcl-xL in cells. Bak BH3  Chemical Structure
  43. GC52344 Bak BH3 (72-87) (human) (trifluoroacetate salt) A Bak-derived peptide Bak BH3 (72-87) (human) (trifluoroacetate salt)  Chemical Structure
  44. GC12053 BAM7 A direct activator of Bax BAM7  Chemical Structure
  45. GN10507 Baohuoside I Baohuoside I  Chemical Structure
  46. GC15371 Bardoxolone An anti-inflammatory compound that activates Nrf2/ARE signaling Bardoxolone  Chemical Structure
  47. GC11572 Bardoxolone methyl A synthetic triterpenoid with potent anticancer and antidiabetic activity Bardoxolone methyl  Chemical Structure
  48. GC60620 Batabulin Batabulin (T138067) is an antitumor agent, which binds covalently and selectively to a subset of the β-tubulin isotypes, thereby disrupting microtubule polymerization. Batabulin affects cell morphology and leads to cell-cycle arrest ultimately induces apoptotic cell death. Batabulin  Chemical Structure
  49. GC60621 Batabulin sodium An inhibitor of tubulin polymerization Batabulin sodium  Chemical Structure
  50. GC12763 Bax channel blocker Bax channel blocker  Chemical Structure
  51. GC16023 Bax inhibitor peptide P5 Bax inhibitor Bax inhibitor peptide P5  Chemical Structure
  52. GC17195 Bax inhibitor peptide V5 A Bax inhibitor Bax inhibitor peptide V5  Chemical Structure
  53. GC52476 Bax Inhibitor Peptide V5 (trifluoroacetate salt) A Bax inhibitor Bax Inhibitor Peptide V5 (trifluoroacetate salt)  Chemical Structure
  54. GC16695 Bax inhibitor peptide, negative control Peptide inhibit Bax translocation to mitochondria Bax inhibitor peptide, negative control  Chemical Structure
  55. GC10345 Bay 11-7085

    NK-κB activation inhibitor

    Bay 11-7085  Chemical Structure
  56. GC13035 Bay 11-7821

    A selective and irreversible NF-κB inhibitor

    Bay 11-7821  Chemical Structure
  57. GC16389 BAY 61-3606 A Syk inhibitor BAY 61-3606  Chemical Structure
  58. GC42897 BAY 61-3606 (hydrochloride) BAY 61-3606 is a cell-permeable, reversible inhibitor of spleen tyrosine kinase (Syk; Ki = 7.5 nM; IC50 = 10 nM). BAY 61-3606 (hydrochloride)  Chemical Structure
  59. GC12136 BAY 61-3606 dihydrochloride BAY 61-3606 dihydrochloride  Chemical Structure
  60. GC62164 BAY1082439 BAY1082439 is an orally bioavailable, selective PI3Kα/β/δ inhibitor. BAY1082439 also inhibits mutated forms of PIK3CA. BAY1082439 is highly effective in inhibiting Pten-null prostate cancer growth. BAY1082439  Chemical Structure
  61. GC16516 BCH BCH (BCH) is a selective and competitive inhibitor of large neutral amino acid transporter 1 (LAT1) significantly inhibit cellular uptake of amino acids and mTOR phosphorylation, which induces the suppression of cancer growth and apoptosis. BCH  Chemical Structure
  62. GC63325 Bcl-xL antagonist 2 Bcl-xL antagonist 2 is a potent, selective, and orally active antagonist of BCL-XL with an IC50 and Ki of 0.091 μM and 65 nM, respectively. Bcl-xL antagonist 2 promotes the apoptosis of cancer cells. Bcl-xL antagonist 2 has the potential for the research of the chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Bcl-xL antagonist 2  Chemical Structure
  63. GC62599 BCL6-IN-4 BCL6-IN-4 is a potent B-cell lymphoma 6 (BCL6) inhibitor with an IC50 of 97 nM. BCL6-IN-4 has anti-tumor activities. BCL6-IN-4  Chemical Structure
  64. GC68012 BCL6-IN-7 BCL6-IN-7  Chemical Structure
  65. GC10721 BDA-366 BDA-366 is a potent Bcl2 antagonist (Ki = 3.3 nM), binding Bcl2-BH4 domain with high affinity and selectivity. BDA-366 induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer cells. BDA-366  Chemical Structure
  66. GC42912 Becatecarin Becatecarin is a water-soluble, diethylaminoethyl analog of the antineoplastic antibiotic rebeccamycin. Becatecarin  Chemical Structure
  67. GC68369 Belantamab Belantamab  Chemical Structure
  68. GC65031 Belimumab Belimumab (LymphoStat B) is a human IgG1λ monoclonal antibody that inhibits B-cell activating factor (BAFF). Belimumab  Chemical Structure
  69. GC49042 Benastatin A A bacterial metabolite with diverse biological activities Benastatin A  Chemical Structure
  70. GC64354 Bendamustine Bendamustine (SDX-105 free base), a purine analogue, is a DNA cross-linking agent. Bendamustine activates DNA-damage stress response and apoptosis. Bendamustine has potent alkylating, anticancer and antimetabolite properties. Bendamustine  Chemical Structure
  71. GC10744 Bendamustine HCl Bendamustine HCl (SDX-105), a purine analogue, is a DNA cross-linking agent. Bendamustine HCl activats DNA-damage stress response and apoptosis. Bendamustine HCl has potent alkylating, anticancer and antimetabolite properties. Bendamustine HCl  Chemical Structure
  72. GC49781 Benomyl A carbamate pesticide Benomyl  Chemical Structure
  73. GC62451 Benpyrine Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine  Chemical Structure
  74. GC49403 Benzarone An active metabolite of benzbromarone Benzarone  Chemical Structure
  75. GC14930 Benzbromarone TMEM16A/B calcium-activated chloride channel (CaCC) blocker Benzbromarone  Chemical Structure
  76. GN10520 Benzoylpaeoniflorin Benzoylpaeoniflorin  Chemical Structure
  77. GC38683 Benzyl isothiocyanate Benzyl isothiocyanate is a member of natural isothiocyanates with antimicrobial activity. Benzyl isothiocyanate  Chemical Structure
  78. GN10358 Berbamine hydrochloride Berbamine hydrochloride  Chemical Structure
  79. GN10539 Bergenin Bergenin  Chemical Structure
  80. GC42925 Berteroin Berteroin is a sulforaphane analog found in cruciferous vegetables including Chinese cabbage, rucola salad leaves, and mustard oil. Berteroin  Chemical Structure
  81. GC10734 Beta-Lapachone Beta-Lapachone (ARQ-501;NSC-26326) is a naturally occurring O-naphthoquinone, acts as a topoisomerase I inhibitor, and induces apoptosis by inhibiting cell cycle progression. Beta-Lapachone  Chemical Structure
  82. GC35504 Beta-Zearalanol Beta-Zearalenol is an mycotoxin produced by Fusarium spp, which causes apoptosis and oxidative stress in mammalian reproductive cells. Beta-Zearalanol  Chemical Structure
  83. GN10632 Betulin Betulin  Chemical Structure
  84. GC10480 Betulinic acid A plant triterpenoid similar to bile acids Betulinic acid  Chemical Structure
  85. GC48477 Betulinic Acid propargyl ester An alkyne derivative of betulinic acid Betulinic Acid propargyl ester  Chemical Structure
  86. GC48504 Betulinic Aldehyde oxime A derivative of betulin Betulinic Aldehyde oxime  Chemical Structure
  87. GC48520 Betulonaldehyde A pentacyclic triterpenoid Betulonaldehyde  Chemical Structure
  88. GC12074 BG45 Novel HDAC3-selective inhibitor BG45  Chemical Structure
  89. GC18136 BH3I-1 Bcl-2 or Bcl-XL inhibitor BH3I-1  Chemical Structure
  90. GC35511 BI-0252 BI-0252 is an orally active, selective MDM2-p53 inhibitor with an IC50 of 4 nM. BI-0252 can induce tumor regressions in all animals of a mouse SJSA-1 xenograft, with concomitant induction of the tumor protein p53 (TP53) target genes and markers of apoptosis. BI-0252  Chemical Structure
  91. GC17828 BI-847325 dual inhibitor of MEK and Aurora kinases BI-847325  Chemical Structure
  92. GC11224 BI6727(Volasertib) BI6727(Volasertib) (BI 6727) is an orally active, highly potent and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with an IC50 of 0.87 nM. BI6727(Volasertib) inhibits PLK2 and PLK3 with IC50s of 5 and 56 nM, respectively. BI6727(Volasertib) induces mitotic arrest and apoptosis. BI6727(Volasertib), a dihydropteridinone derivative, shows marked antitumor activity in multiple cancer models. BI6727(Volasertib)  Chemical Structure
  93. GC13636 BIBR 1532 Telomerase inhibitor,novel and selective BIBR 1532  Chemical Structure
  94. GC60076 Bigelovin Bigelovin, a sesquiterpene lactone isolated from Inula helianthus-aquatica, is a selective retinoid X receptor α agonist. Bigelovin suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation. Bigelovin  Chemical Structure
  95. GC15987 BIM, Biotinylated

    Bim peptide fragment with a biotin moiety attached

    BIM, Biotinylated  Chemical Structure
  96. GC49513 Bim/BOD (IN) Polyclonal Antibody For immunodetection of Bim-related proteins Bim/BOD (IN) Polyclonal Antibody  Chemical Structure
  97. GC52355 BimS BH3 (51-76) (human) (trifluoroacetate salt) A Bim-derived peptide BimS BH3 (51-76) (human) (trifluoroacetate salt)  Chemical Structure
  98. GC14233 BIO-acetoxime

    GSK-3α/β inhibitor

    BIO-acetoxime  Chemical Structure
  99. GC67680 BIO8898 BIO8898  Chemical Structure
  100. GC18476 Biotin-VAD-FMK Biotin-VAD-FMK is a biotin-conjugated form of the pan-caspase inhibitor Z-VAD(OH)-FMK . Biotin-VAD-FMK  Chemical Structure
  101. GC35523 Bioymifi A DR5 agonist Bioymifi  Chemical Structure

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