2. Signaling Pathways
  3. Apoptosis
  4. Bcl-2 Family

Bcl-2 Family

Bcl-2 Family

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Bcl-2 is a family of evolutionarily related proteins. These proteins govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro-apoptotic (Bax, Bad, Bak and Bok among others) or anti-apoptotic (including Bcl-2 proper, Bcl-xL, and Bcl-w, among an assortment of others). There are a total of 25 genes in the Bcl-2 family known to date. Human genes encoding proteins that belong to this family include: Bak1, Bax, Bal-2, Bok, Mcl-1.

Bcl-2 Family Isoform Specific Products:

Bcl-2 Family Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-109184
    Murizatoclax
    		Inhibitor 98.85%
    Murizatoclax (AMG 397) is a potent, selective and orally active inhibitor of myeloid leukemia 1 (MCL-1) inhibitor, with a Ki of 15 pM. Murizatoclax competitive binds to the BH3-binding groove of MCL1 with pro-apoptotic BCL-2 family members. Murizatoclax can be used for the research of cancer.
    Murizatoclax
  • HY-100383
    BH3I-1
    		Inhibitor ≥98.0%
    BH3I-1 is a Bcl-2 family antagonist, which inhibits the binding of the Bak BH3 peptide to Bcl-xL with a Ki of 2.4±0.2 μM in FP assay. BH3I-1 has a Kd of 5.3 μM against the p53/MDM2 pair.
    BH3I-1
  • HY-119931
    2-Hydroxychalcone
    		Inhibitor 98.80%
    2-hydroxychalcone, a natural flavonoid, is a potent antioxidant, inhibiting lipid peroxidation. 2-Hydroxychalcone induces apoptosis by Bcl-2 downregulation. 2-Hydroxychalcone inhibits the activation of NF-kB.
    2-Hydroxychalcone
  • HY-121337
    Flurochloridone
    		Activator 99.61%
    Flurochloridone (R-40244) is a selective preemergence and persistent herbicide. Flurochloridone induces endoplasmic reticulum (ER) stress and activated unfolded protein response (UPR) signaling pathways. Flurochloridone impairs cell viability and induces cytotoxicity and apoptosis mediated by ER stress via activating eIF2α-ATF4/ATF6-CHOP-Bim/Bax signaling pathways in TM4 cells.
    Flurochloridone
  • HY-B0862
    Pendimethalin
    		Inhibitor 99.75%
    Pendimethalin is an orally active herbicide that controls annual grasses and certain broadleaf weeds. Pendimethalin induces Apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells.
    Pendimethalin
  • HY-P1562
    PUMA BH3
    		Activator 98.24%
    PUMA BH3 is a p53 upregulated modulator of apoptosis (PUMA) BH3 domain peptide, acts as a direct activator of Bak, with a Kd of 26 nM.
    PUMA BH3
  • HY-N2067
    Vanillyl alcohol
    		99.68%
    Vanillyl alcohol (p-(Hydroxymethyl)guaiacol) is an orally active phenolic alcohol. Vanillyl alcohol reduces ROS generation. suppresses Bax, increases Bcl-2. Vanillyl alcohol has anti-angiogenic, anti-inflammatory, anti-nociceptive and neuroprotective effects. Vanillyl alcohol is used as a flavoring agent in foods and beverages.
    Vanillyl alcohol
  • HY-12527
    Pyridoclax
    		Inhibitor 99.95%
    Pyridoclax is a potential Mcl-1 inhibitor.
    Pyridoclax
  • HY-142209
    ABBV-167
    		Inhibitor 98.10%
    ABBV-167 is a phosphate proagent of the BCL-2 inhibitor venetoclax.
    ABBV-167
  • HY-119402
    TP-021
    		Inhibitor 99.14%
    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.
    TP-021
  • HY-B2046
    Simazine
    		Inhibitor 99.72%
    Simazine is a triazine herbicide. Simazine is widely used in agriculture, potted plant and tree production. In addition, Simazine can induce the apoptosis of immune cells in the spleen of mice and inhibit the proliferation of B cells and T cells in mice.
    Simazine
  • HY-14521A
    Lometrexol disodium
    		Inducer ≥98.0%
    Lometrexol (DDATHF) disodium, an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol disodium can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol disodium has anticancer activity. Lometrexol disodium also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor.
    Lometrexol disodium
  • HY-160438B
    PBX-7011 TFA
    		Inhibitor 98.60%
    PBX-7011 TFA is a derivative of camptothecin (HY-16560), which inhibits expressions of the cancer related survival genes DDX5, Survivin, Mcl-1 and XIAP in cells FaDu, degrades DDX5 proteins and exhibits anticancer activity.
    PBX-7011 TFA
  • HY-16014
    A-385358
    		Inhibitor 98.19%
    A-385358 is a selective inhibitor of Bcl-XL with Kis of 0.80 and 67 nM for Bcl-XL and Bcl-2, respectively.
    A-385358
  • HY-15464D
    (S)-Gossypol (acetic acid)
    		Inhibitor 98.39%
    (S)-Gossypol is the isomer of a natural product Gossypol. (S)-Gossypol binds to the BH3-binding groove of Bcl-xL and Bcl-2 proteins with high affinity.
    (S)-Gossypol (acetic acid)
  • HY-157176
    BAX-IN-1
    		Inhibitor 98.05%
    BAX-IN-1 is a potential, selective inhibitor of Bcl-2-associated X protein (BAX).
    BAX-IN-1
  • HY-115718
    PZ703b
    		Degrader 98.00%
    PZ703b is a Bcl-xl PROTAC degrader that induces apoptosis and inhibits cancer cell proliferation. PZ703b can be used for the research of bladder cancer research.
    PZ703b
  • HY-N0905
    Ginsenoside Rh4
    		Activator 99.28%
    Ginsenoside Rh4 is a rare saponin obtained from Panax notoginseng. Ginsenoside Rh4 activates Bax, caspase 3, caspase 8, and caspase 9. Ginsenoside Rh4 also induces autophagy.
    Ginsenoside Rh4
  • HY-115532
    BCL6-IN-7
    		Inhibitor 99.79%
    BCL6-IN-7 is a potent BCL6−corepressor interaction inhibitor.
    BCL6-IN-7
  • HY-138697
    S65487
    		Inhibitor 99.91%
    S65487 (VOB560), a potent and selective BCL-2 inhibitor, is a proagent of S55746. S65487 is also active on BCL-2 mutations, such as G101V and D103Y. S65487 has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 induces apoptosis and has anticaner activities.
    S65487
Cat. No. Product Name / Synonyms Application Reactivity
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Download Bcl-2 Family Signaling Pathway Map.

Bcl-2 family members have been grouped into three classes. The anti-apoptotic subfamily contains the Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B proteins, which suppress apoptosis and contain all four Bcl-2 homology domains, designated BH1-4. The pro-apoptotic subfamily contain BH1-3 domains, such as Bax, Bak, and Bok. A third class of BH3 only proteins Bad, Bid, Bim, Noxa and Puma have a conserved BH3 domain that can bind and regulate the anti-apoptotic BCL-2 proteins to promote apoptosis [1].


The intrinsic pathway is initiated by various signals, principally extracellular stimuli. BH3-only proteins (Bim, Bid, Bad, Noxa, Puma) engage with anti-apoptotic Bcl-2 family proteins to relieve their inhibition of Bax and Bak to activate them. Next, Bax and Bak are oligomerized and activated, leading to mitochondrial outer membrane permeabilization. Once mitochondrial membranes are permeabilized, cytochrome c and/or Smac/DIABLO is released into the cytoplasm, wherein they combine with an adaptor molecule, Apaf-1, and an inactive initiator Caspase, Pro-caspase 9, within a multiprotein complex called the apoptosome. Smac/DIABLO inhibits IAPs to activate Caspase 9. Caspase 9 activates Caspase 3, which is the initiation step for the cascade of Caspase activation. The extrinsic pathway can be activated by cell surface receptors, such as Fas and TNF Receptor, subsequently activating Caspase 8, and leads to Caspase 3 activation and cell demolition. Caspases in turn cleave a series of substrates, activate DNases and orchestrate the demolition of the cell. Bcl-2 family proteins are also found on the endoplasmic reticulum and the perinuclear membrane in hematopoietic cells, but they are predominantly localized to mitochondria [2]. 

 

Reference:
[1]. Cotter TG, et al. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer. 2009 Jul;9(7):501-7.

[2]. Kang MH, et al. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res. 2009 Feb 15;15(4):1126-32.

Bcl-2 Family Isoform Comparison

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