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-B1971S1
    Deltamethrin-d6
    Deltamethrin-d6 (Decamethrin-d6) is deuterium labeled Deltamethrin. 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-d<sub>6</sub>
  • HY-N15378
    β-Carotene-15,15'-epoxide
    		Inhibitor
    β-carotene-15,15ʹ-epoxide is a XIAP antagonist with apoptosis-inducing and antitumor activity, found in the leaves of Spondias mombin. In a DMBA (HY-W011845)-induced rat model of breast cancer, β-carotene-15,15ʹ-epoxide binds to the BIR3 domain of the anti-apoptotic protein XIAP, blocking its interaction with caspase-9 and thereby promoting tumor cell apoptosis. In addition, β-carotene-15,15ʹ-epoxide significantly downregulates the expression of BCL-2, COX-2, and TNF-α in tumor tissues, reduces MDA levels, increases catalase activity, and modulates serum levels of LDH, ALP, and ALT, demonstrating strong antioxidant, anti-inflammatory, and metabolic protective effects. β-carotene-15,15ʹ-epoxide may be used in research on inflammation-related conditions and cancers such as breast cancer.
    β-Carotene-15,15'-epoxide
  • HY-10087R
    Navitoclax (Standard)
    		Inhibitor
    Navitoclax (Standard) is the analytical standard of Navitoclax. This product is intended for research and analytical applications. Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-xL, Bcl-2 and Bcl-w, with a Ki of less than 1 nM.
    Navitoclax (Standard)
  • HY-15531S1
    Venetoclax-d6
    		Inhibitor
    Venetoclax-d6 (ABT-199-d6) 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>6</sub>
  • HY-167881
    MLS-0053105
    		Inhibitor
    MLS-0053105, a chloromaleimide, is a selective BFL-1 inhibitor with an IC50 of 0.4 µM for Bfl-1/F-Bid. MLS-0053105 shows over 10 times less potent inhibition of Bcl-W, Bcl-2, and Bcl-XL and no activity against Bcl-B and Mcl-1.
    MLS-0053105
  • HY-N8508
    Myrothecine A
    		Inducer
    Myrothecine A is a trichothecene mycotoxin found in M. roridum. Myrothecine A induces apoptosis, promotes the cytochrome c release, PARP-cleavage and phosphorylation of JNK, increases Bax and cleaved caspase-3, -5, and -8 levels. Myrothecine A has anticancer activities and promotes the maturation of DC cells in the microenvironment. Myrothecine A inhibits proliferation of A549, MCF-7, HepG2, and SMMC-7721 cancer cells with IC50s of 95, 70, 60, and 25 µM, respectively.
    Myrothecine A
  • HY-165537
    Siphonaxanthin
    		Inhibitor
    Siphonaxanthin is a keto-carotenoid with anti-angiogenic and anti-inflammatory activity, which is found in green algae. Siphonaxanthin upregulates the expression of death receptor 5 (DR5), induces cancer cell apoptosis, decreases the expression of Bcl-2, and activates caspase-3. Siphonaxanthin is also an inhibitor of FGFR-1. Siphonaxanthin inhibits the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as the outgrowth of microvessels in the rat aortic ring. Siphonaxanthin is promising for research of diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis.
    Siphonaxanthin
  • HY-B0402AR
    Amantadine hydrochloride (Standard)
    		Modulator
    Amantadine (hydrochloride) (Standard) is the analytical standard of Amantadine (hydrochloride). This product is intended for research and analytical applications. 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 (Standard)
  • HY-N2014R
    Verbenalin (Standard)
    Verbenalin (Standard) is the analytical standard of Verbenalin. This product is intended for research and analytical applications. 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 (Standard)
  • HY-N2067R
    Vanillyl alcohol (Standard)
    Vanillyl alcohol (Standard) is the analytical standard of Vanillyl alcohol (HY-N2067). This product is intended for research and analytical applications. 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 (Standard)
  • HY-B1135R
    Benzbromarone (Standard)
    Benzbromarone (Standard) is the analytical standard of Benzbromarone. This product is intended for research and analytical applications. Benzbromarone is an orally active anti-gout agent. Benzbromarone has anti-infammatory, anti-oxidative stress and nephroprotective effects. Benzbromarone can be used for the research of hyperuricemia and gout.
    Benzbromarone (Standard)
  • HY-117136
    AN-7
    AN-7 is an orally active histone deacetylase (HDAC) inhibitor that induces histone hyperacetylation and differentiation in vitro and in vivo, and inhibits the proliferation of human prostate 22Rv1 cancer cells. AN-7 can increase the expression of the pro-apoptotic protein Bax, reduce the expression of the anti-apoptotic protein Bcl-2, and promote apoptosis by activating caspase-3, and can be used in the study of prostate cancer.
    AN-7
  • HY-124284R
    Hexamethylene bisacetamide (Standard)
    		Inhibitor
    Hexamethylene bisacetamide (Standard) is the analytical standard of Hexamethylene bisacetamide. This product is intended for research and analytical applications. 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 (Standard)
  • HY-116532
    YCW-E11
    		Inhibitor
    YCW-E11 is a Bcl-2, and Mcl-1 inhibitor with Ki values of 0.83 and 0.33 μM, respectively. YCW-E11 induces cell apoptosis through the mitochondrial pathway and exhibits antitumor activity. YCW-E11 can be utilized in cancer research.
    YCW-E11
  • HY-121337R
    Flurochloridone (Standard)
    		Activator
    Flurochloridone (Standard) is the analytical standard of Flurochloridone. This product is intended for research and analytical applications. 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 (Standard)
  • HY-W286906
    Mcl1-IN-15
    		Inhibitor
    Mcl1-IN-15 (Compound 7) is the inhibitor for myeloid cell leukemia 1 (Mcl-1) with an IC50 of 8.73 μM. Mcl1-IN-15 inhibits Mcl1-BH3 peptide interaction, activates the Bak/Bax-mediated apoptosis and exhibits antitumor activity.
    Mcl1-IN-15
  • HY-B2046R
    Simazine (Standard)
    		Inhibitor
    Simazine (Standard) is the analytical standard of Simazine (HY-B2046). This product is intended for research and analytical applications. 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 (Standard)
  • HY-N15424
    Himachalol
    Himachalol, a sesquiterpene, is an orally active antispasmodic and anticancer constituent found in the wood of Cedrus deodara. Himachalol has anti-proliferative activity against the melanoma cells, and induces apoptosis (decreases Bcl-2 level and increases Bax level). Himachalol has systemic hypotension and peripheral vasodilation effect. Himachalol inhibits Carbachol-induced spasm of the intestine. The LD50 of Himachalol in mice is 265 mg/kg (p.o.) and 247 mg/kg (i.p.).
    Himachalol
  • HY-119009
    TM-233
    		Inhibitor
    TM-233 is an inhibitor of the JAK/STAT and NF-κB signaling pathways, exhibiting significant antitumor activity. TM-233 reduces the expression of the anti-apoptotic protein Mcl-1 by inhibiting the phosphorylation of JAK2 and STAT3, and regulates its transcription by directly binding to the Mcl-1 gene promoter. Additionally, TM-233 prevents the translocation of NF-κB from the cytoplasm to the nucleus by inhibiting its DNA-binding activity, thereby reducing nuclear NF-κB expression. TM-233 shows potential in overcoming Bortezomib (HY-10227) resistance and can be applied in research related to multiple myeloma.
    TM-233
  • HY-103243R
    TCPOBOP (Standard)
    		Inhibitor
    TCPOBOP (Standard) is the analytical standard of TCPOBOP. This product is intended for research and analytical applications. 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 (Standard)
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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