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-147081
    AS 1411
    		Inhibitor 99.52%
    AS 1411 (AGRO-100) is an oligonucleotide aptamer targeting nucleoproteins. AS 1411 inhibits tumor cell proliferation by affecting the activity of nucleoprotein-containing complexes and can be used as a carrier to precisely deliver nanoparticles, oligonucleotides and small molecules to cancer cells. AS 1411 reduces PRMT5 expression to inhibit tumor growth in DU145 prostate cancer cells. AS 1411 works by blocking the binding of nucleoproteins to bcl-2 mRNA in MCF-7 breast cancer cells. AS 1411-coupled Jin nanospheres can inhibit breast cancer cell proliferation in vitro and in mouse models, has the ability to cross the blood-brain barrier with low tissue toxicity.
    AS 1411
  • HY-N0213
    Peiminine
    		99.94%
    Peiminine is a compound that can be isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family). Peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways. Peiminine has anti-inflammatory, anticancer, anti-osteoporosis, cardioprotective and other activities in many animal models.
    Peiminine
  • HY-B0987
    Ascorbyl palmitate
    		Inhibitor 99.62%
    Ascorbyl palmitate is an orally active ester formed from ascorbic acid and palmitic acid, used as an antioxidant and food additive. Ascorbyl palmitate in preventing fat and oil oxidation is more efficient than Butylated hydroxyanisole (HY-B1066) and Butylated hydroxytoluene (HY-Y0172). Ascorbyl palmitate mitigates inhibition of collagen synthesis by select calcium and sodium channel blockers. Ascorbyl palmitate induces Apoptosis in human umbilical vein endothelial cells (HUVECs). Ascorbyl palmitate ameliorates inflammatory diseases by inhibition of NLRP3 inflammasome.
    Ascorbyl palmitate
  • HY-150069
    UBX1325
    		Inhibitor 99.16%
    UBX1325 is an Bcl-xL inhibitor that promotes apoptosis in senescent cells. UBX1325 is a potent anti-aging agent that can be used in studies of age-related eye diseases such as diabetic macular oedema (DME), age-related macular degeneration (AMD) and diabetic retinopathy (DR).
    UBX1325
  • HY-126741
    Azadirachtin
    		Inhibitor 99.06%
    Azadirachtin is an oral active triterpenoid compound with anticancer, antimalarial, anti-inflammatory, and insecticidal activities. Azadirachtin induces cell apoptosis through the mitochondrial pathway (by inhibiting Bcl-2/Bax ratio or activating Apaf-1 and caspase-3) or through death receptors (by inhibiting TNFR activation). Additionally, Azadirachtin exerts its anti-inflammatory effects by inhibiting NF-кB signaling pathway activation, and it exhibits insecticidal activity by inducing apoptosis in insect cells.
    Azadirachtin
  • HY-N2897
    Dihydrokaempferol
    		Inhibitor 99.88%
    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 agents.
    Dihydrokaempferol
  • HY-N3584
    Paris saponin VII
    		Inhibitor 99.96%
    Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia.
    Paris saponin VII
  • HY-15531S
    Venetoclax-d8
    		Inhibitor 99.76%
    Venetoclax-d8 is deuterium labeled Venetoclax. Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a Ki of less than 0.01 nM. Venetoclax induces autophagy.
    Venetoclax-d<sub>8</sub>
  • HY-125877
    PROTAC Mcl1 degrader-1
    		Inhibitor 98.13%
    PROTAC Mcl1 degrader-1 (compound C3), a proteolysis targeting chimera (PROTAC) based on Cereblon ligand, is a potently and selectively Mcl-1 (Bcl-2 family member) inhibitor with an IC50 of 0.78 μM. PROTAC Mcl1 degrader-1 inhibits Bcl-2 with an IC50 of 0.54 μM.
    PROTAC Mcl1 degrader-1
  • HY-125876
    PROTAC Bcl2 degrader-1
    		Inhibitor 99.80%
    PROTAC Bcl2 degrader-1 (Compound C5) is a PROTAC based on Cereblon ligand, which potently and selectively induces the degradation of Bcl-2 (IC50, 4.94 μM; DC50, 3.0 μM) and Mcl-1 (IC50, 11.81 μM) by introducing the E3 ligase cereblon (CRBN)-binding ligand pomalidomide to Mcl-1/Bcl-2 dual inhibitor Nap-1 (Blue: CRBN ligand, Black: linker；Pink: Mcl-1/Bcl-2 inhibitor, Nap-1).
    PROTAC Bcl2 degrader-1
  • HY-B0621
    Triclabendazole
    		99.36%
    Triclabendazole is an orally active parasite inhibitor. Triclabendazole has anti-Leishmania activity and induces gasdermin E (GSDME)-dependent pyroptosis by caspase-3 activation. Triclabendazole can be used for the research of fasciola hepatica.
    Triclabendazole
  • HY-118341
    Clitocine
    		Inhibitor
    Clitocine, an adenosine nucleoside analog isolated from mushroom, is a potent and efficacious readthrough agent. Clitocine acts as a suppressor of nonsense mutations and can induce the production of p53 protein in cells harboring p53 nonsense-mutated alleles. Clitocine can induce apoptosis in multidrug-resistant human cancer cells by targeting Mcl-1. Anticancer activity.
    Clitocine
  • HY-103243
    TCPOBOP
    		Inhibitor 99.70%
    TCPOBOP is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.
    TCPOBOP
  • HY-17583
    Griseofulvin
    		98.93%
    Griseofulvin is an orally active antifungal antibiotic with antitumor activity. Griseofulvin induces apoptosis and G2/M cell cycle arrest in cancer cells. Griseofulvin also has cardiovascular modulatory activity, reducing angina pectoris, relieving hand artery spasm associated with onychomycosis, and peripheral vascular diseases such as shoulder-hand syndrome.
    Griseofulvin
  • HY-B0766
    Bicyclol
    		99.91%
    Bicyclol (SY801) is an orally active derivative of the traditional Chinese medicine Schisandra chinensis, which has antiviral, anti-inflammatory, immunomodulatory, antioxidant, anti-steatosis, anti-fibrotic and anti-tumor activities. Bicyclol regulates the expression of heat shock proteins and plays an anti-apoptosis role in hepatocytes. Bicyclol reduces the activation of NF-κB and the levels of inflammatory factors in hepatocytes infected with hepatitis C virus (HCV) by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and prevents ferroptosis in acute liver injury. Bicyclol can change the expression of Mdr-1, GSH/GST and Bcl-2, increase the intracellular concentration of anticancer drugs, and sensitize drug-resistant cells to anticancer drugs. Bicyclol inhibits the proliferation of human malignant hepatoma cells by regulating the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway. Bicyclol can be used in the study of chronic hepatitis, acute liver injury, nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma.
    Bicyclol
  • HY-114118F
    Semaglutide, FITC labeled
    		99.83%
    Semaglutide, FITC labeled is a long-acting, selective, competitive, orally active GLP-1R agonist that can penetrate the blood-brain barrier. After activating GLP-1R, Semaglutide, FITC labeled promotes insulin secretion, inhibits gastric emptying and appetite, and at the same time enhances autophagy, inhibits oxidative stress and apoptosis. Semaglutide, FITC labeled also regulates mitochondrial function and lipid metabolism (such as reducing de novo lipogenesis in the liver). Semaglutide, FITC labeled has activities such as lowering blood sugar, reducing weight, neuroprotection (such as improving motor function in Parkinson's disease models, reducing α-synuclein aggregation) and improving hepatic steatosis. Semaglutide, FITC labeled can be used for the study of neurodegenerative diseases and liver diseases such as type 2 diabetes, obesity, Parkinson's disease, metabolic associated fatty liver disease (MASLD), and cancer.
    Semaglutide, FITC labeled
  • HY-13755A
    (R)-Sulforaphane
    		Inhibitor 99.48%
    (R)-Sulforaphane (L-Sulforaphane) is a orally active, potent inducer of the Keap1/Nrf2/ARE pathway, exhibiting antioxidant and anticancer activities. (R)-Sulforaphane primarily functions by upregulating phase II detoxifying enzymes in cells, aiding in the removal of carcinogens and combating oxidative stress. (R)-Sulforaphane is capable of modulating gene expression, influencing various signaling pathways, including Nrf2, NF-κB, and AP-1. (R)-Sulforaphane can be used in studies of tumor biology, antioxidant defense mechanisms, as well as inflammation and immune responses.
    (R)-Sulforaphane
  • HY-W050044
    L-Azetidine-2-carboxylic acid
    		Activator 99.85%
    L-Azetidine-2-carboxylic acid is a proline analog. L-Azetidine-2-carboxylic acid upregulates the lipid autophagy marker LC3-II via activation of the PERK pathway. L-Azetidine-2-carboxylic acid increases pro-apoptotic BAX protein. L-Azetidine-2-carboxylic acid induces ATF6 cleavage and upregulates phosphorylated eIF2α levels. L-Azetidine-2-carboxylic acid induces ER stress, inducing protein misfolding and aggregation. L-Azetidine-2-carboxylic acid shows teratogenic, pro-inflammatory and pro-apoptotic effects.
    L-Azetidine-2-carboxylic acid
  • HY-123054
    BTSA1
    		Activator 99.77%
    BTSA1 is a potent, high affinity and orally active BAX activator with an IC50 of 250 nM and an EC50 of 144 nM. BTSA1 binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis.
    BTSA1
  • HY-N2014
    Verbenalin
    		99.91%
    Verbenalin is an orally active terpenoid glycoside that can be extracted from the medicinal plant Verbena officinalis. Verbenalin has anti-inflammatory, antiviral, and neuroprotective effects. Verbenalin has a strong binding affinity to the nsp-12 protein of the SARS-CoV-2 virus. Verbenalin can be used in the research of inflammatory and nervous system diseases such as hepatitis and Alzheimer's disease.
    Verbenalin
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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