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-17510
    Gossypol (acetic acid)
    		Inhibitor 99.75%
    Gossypol acetic acid ((±)-Gossypol-acetic acid) binds to Bcl-xL protein and Bcl-2 protein with Kis of 0.5-0.6 μM and 0.2-0.3 mM, respectively.
    Gossypol (acetic acid)
  • HY-124284
    Hexamethylene bisacetamide
    		Inhibitor 99.56%
    Hexamethylene bisacetamide (HMBA) is a differentiation inducer and selective bromine domain inhibitor that can differentiate across the blood-brain barrier. Hexamethylene bisacetamide can induce tumor cell differentiation and inhibit cell proliferation, showing antitumor activity. Hexamethylene bisacetamide induces apoptosis by Notch1, Bcl-2 and p53 signaling pathways. In addition, Hexamethylene bisacetamide improves the obesity phenotype of mice.
    Hexamethylene bisacetamide
  • HY-B1971
    Deltamethrin
    		99.93%
    Deltamethrin (Decamethrin) is an orally active synthetic pyrethroid insecticide. Deltamethrin induces oxidative stress and results in inflammation and apoptosis via inhibiting Nrf2/HO-1 pathway. Deltamethrin has an anticancer effect by inducing apoptosis. Deltamethrin can be used extensively in pest control.
    Deltamethrin
  • 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-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-129960
    L-Selenocystine
    		98.0%
    L-Selenocystine is a selenium-containing amino acid. L-Selenocystine has redox properties. L-Selenocystine is cytotoxic to various tumor cells and can induce the production of ROS and apoptosis. L-Selenocystine can block the Nrf2 and autophagy pathways. L-Selenocystine has anti-tumor activity.
    L-Selenocystine
  • HY-W250122
    Glutamic acid sodium salt
    		Activator 99.23%
    Glutamic acid sodium salt (Monosodium glutamate) is an orally active food flavor enhancer. Glutamic acid sodium salt causes ROS generation, mitochondrial dysfunction, and Apoptosis. Glutamic acid sodium salt upregulates CHOP, Grp78, and Bcl-2. Glutamic acid sodium salt impairs cognition, induces depressive-like behavior, induces hyperalgesia, and induces obesity and insulin resistance. Glutamic acid sodium salt can be used to study neurotoxicity (e.g., brain damage, cognitive impairment), metabolic disorders (e.g., obesity, insulin resistance), hepatotoxicity, and renal toxicity, as well as pain-related disorders.
    Glutamic acid sodium salt
  • 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-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-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-N2897
    Dihydrokaempferol
    		Inhibitor 99.84%
    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-B0402A
    Amantadine hydrochloride
    		Modulator 98.0%
    Amantadine (1-Adamantanamine) hydrochloride is an orally avtive and potent antiviral agent with activity against influenza A viruses. Amantadine hydrochloride inhibits several ion channels such as NMDA and M2, and also inhibits Coronavirus ion channels. Amantadine hydrochloride also has anti-orthopoxvirus and anticancer activity. Amantadine hydrochloride can be used for Parkinson's disease, postoperative cognitive dysfunction (POCD) and COVID-19 research.
    Amantadine hydrochloride
  • 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-114118B
    Semaglutide acetate
    		99.92%
    Semaglutide acetate is a long-acting, selective, competitive GLP-1R agonist that can penetrate the blood-brain barrier. After activating GLP-1R, Semaglutide acetate promotes insulin secretion, inhibits gastric emptying and appetite, and at the same time enhances autophagy, inhibits oxidative stress and apoptosis. Semaglutide acetate also regulates mitochondrial function and lipid metabolism (such as reducing de novo lipogenesis in the liver). Semaglutide acetate 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 acetate 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 acetate
  • HY-111381
    BI-3812
    		Inhibitor 99.26%
    BI-3812, a chemical probe, is a highly efficient BCL6 inhibitor that is capable of suppressing the BTB domain of BCL6, with an IC50 value of ≤ 3 nM, exhibiting antitumor activity.
    BI-3812
  • 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-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-155956
    GM-90257
    		Inhibitor 99.90%
    GM-90257 is a microtubule acetylation inhibitor. GM-90257 binds directly to α-tubulin. GM-90257 prevents the recruitment of α-tubulin acetyltransferase 1 (αTAT1) to the K40 residue in α-tubulin. GM-90257 causes Apoptosis, downregulates BCl-2, and activates JNK and PARP. GM-90257 has anticancer activity against breast cancer.
    GM-90257
  • 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-102027
    FX1
    		Inhibitor 98.0%
    FX1 is a potent and specific BCL6 inhibitor, with an IC50 of around 35 μM.
    FX1
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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