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-168983
    Lonitoclax
    		Inhibitor
    Lonitoclax is a B-cell lymphoma 2 (Bcl-2) inhibitor. Lonitoclax has comparable anti-tumor efficacy to Venetoclax (HY-15531) in both B cell and myeloid malignancy models. Lonitoclax is promising for research of relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and certain low-grade lymphomas.
    Lonitoclax
  • HY-B1311R
    Proadifen hydrochloride (Standard)
    		Inhibitor
    Proadifen (hydrochloride) (Standard) is the analytical standard of Proadifen (hydrochloride). This product is intended for research and analytical applications. Proadifen (SKF-525A) hydrochloride is a non-competitive Cytochrome P450 inhibitor with an IC50 value of 19 μM. Proadifen hydrochloride reduces monoamine oxidase A (MAO-A) activity and reverses the antidepressantlike behavioral effect of Imipramine (HY-B1490A) and Desipramine (HY-B1272A) in rats. Proadifen hydrochloride also reduces N, N-dimethyltryptamine (DMT) metabolism in liver microsomes and inhibits N-demethylationand Acridone (HY-W007771) formation. Proadifen hydrochloride augments Lipopolysaccharide (LPS) (HY-D1056)-induced fever and exacerbates Prostaglandin E2 (PGE2) (HY-101952) levels in the rat. Proadifen hydrochloride is promising for research of metabolism-related deseases, ovarian carcinoma, inflammation and dopamine neurons-related deseases[4].
    Proadifen hydrochloride (Standard)
  • HY-RS01422
    Bcl2l1 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Bcl2l1 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Bcl2l1 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Bcl2l1 Mouse Pre-designed siRNA Set A
  • HY-161274
    Bfl-1-IN-1
    		Inhibitor
    Bfl-1-IN-1 (Compound 15) is a potent and selective Bfl-1 inhibitor. Bfl-1-IN-1 inhibits Bfl-1 and Mcl-1 with Kis of 0.63 and 6.77 μM, respectively.
    Bfl-1-IN-1
  • HY-N0213R
    Peiminine (Standard)
    Peiminine (Standard) is the analytical standard of Peiminine. This product is intended for research and analytical applications. 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 (Standard)
  • HY-144792
    Bcl-2-IN-7
    		Modulator
    Bcl-2-IN-7 (compound 6) is a potent Bcl-2 (B-cell lymphoma-2) inhibitor. Bcl-2-IN-7 down-regulates the expression of Bcl-2, and increases the expression of p53, Bax, and caspase-7 mRNA. Bcl-2-IN-7 induces cell cycle arrest and apoptosis in breast cancer MCF-7 cells. Bcl-2-IN-7 shows good anticancer activity, with IC50 values of 20.17, 22.64, 45.57, and 51.50 μM against MCF-7, LoVo, HepG2, and A549 cell lines, respectively.
    Bcl-2-IN-7
  • HY-N0060BR
    (E)-Ferulic acid (Standard)
    		Activator
    (E)-Ferulic acid (Standard) is the analytical standard of (E)-Ferulic acid. This product is intended for research and analytical applications. (E)-Ferulic acid is an isomer of ferulic acid, an aromatic compound abundant in plant cell walls. (E)-Ferulic acid causes phosphorylation of β-catenin (β-catenin), leading to proteasome degradation, increasing the expression of pro-apoptotic factor Bax and reducing pro-apoptotic factor Expression of the survival factor survivin. (E)-Ferulic acid can effectively remove reactive oxygen species (ROS) and inhibit lipid peroxidation. (E)-Ferulic acid exerts antiproliferative and antimigratory effects in the human lung cancer cell line H1299.
    (E)-Ferulic acid (Standard)
  • HY-174876
    PZ671
    		Degrader
    PZ671 is a potent Bcl-xL PROTAC degrader with an IC50 of 1.3 nM (MOLT-4 cells) and a DC50 of 0.9 nM (Bcl-xL). PZ671 induces apoptosis in MOLT-4 cells. PZ671 effectively inhibits tumor growth and rapidly reverses transient platelet counts reduction in MOLT-4 xenograft mice. PZ671 can be used for the research of cancer, such as small cell lung cancer (SCLC). (Structure Note: Pink: Bcl-xL ligand (HY-174878); Blue: CRBN Ligand (HY-138793); Black: linker; E3-linker (HY-174879))
    PZ671
  • HY-126311
    4-Hydroxyresveratrol
    		Inducer
    4-Hydroxyresveratrol (3,4,5,4'-Tetrahydroxystibene), a Resveratrol (HY-16561) analog, differentially induces pro-apoptotic p53/Bax gene expression. 4-Hydroxyresveratrol induces apoptosis in SV40 virally transformed WI38 cells (WI38VA) cells, but not in WI38 cells. 4-Hydroxyresveratrol significantly induces the expression of p53, GADD45 and Bax genes and concomitantly suppresses the expression of bcl-2 gene in WI38VA.
    4-Hydroxyresveratrol
  • HY-131188
    PROTAC Bcl-xL degrader-1
    		Inhibitor
    PROTAC Bcl-xL degrader-1 is a PROTAC that comprises a Bcl-xL (Bcl-2 family member) ligand binding group, a linker and an IAP E3 ligases binding group. PROTAC Bcl-xL degrader-1 is a potent Bcl-xL degrader, and shows toxicity for human platelets and MyLa 1929 cells with IC50 values of 62 nM and 8.5 μM, respectively.
    PROTAC Bcl-xL degrader-1
  • HY-152173
    HDAC-IN-51
    		Modulator
    HDAC-IN-51 is a potent histone deacetylase (HDAC) inhibitor with IC50 values of 0.32, 0.353, 0.431, 0.515, and 85.4 μM for HDAC10, HDAC1, HDAC2, HDAC3 and HDAC11, respectively. HDAC-IN-51 induces cell cycle arrest and apoptosis, modulating cell cycle-/apoptosis-related miRNAs expression. HDAC-IN-51 can be used in research of cancer.
    HDAC-IN-51
  • HY-129701
    MCL-1/BCL-2-IN-3
    		Inhibitor 99.22%
    MCL-1/BCL-2-IN-3 (Compound 2) is a potent and selective Mcl-1 and Bcl-2 dual inhibitor with IC50s of 5.95 and 4.78 μM, respectively.
    MCL-1/BCL-2-IN-3
  • HY-144778
    IDO1/TDO-IN-1
    IDO1/TDO-IN-1 (30) is a potent dual IDO1 (uncompetitive, Ki of 0.23 μM) and TDO (competitive, Ki of 0.73 μM) inhibitor. IDO1/TDO-IN-1 (30) significantly promotes cell apoptosis through the potential mitochondria-mediated Bcl-2/Bax pathway.
    IDO1/TDO-IN-1
  • HY-163435
    Anticancer agent 201
    		Inhibitor
    Anticancer agent 201 (Compound 2f) has IC50 values in the low micromolar range for multiple tumor cell lines. Anticancer agent 201 is highly cytotoxic to CCRF-CEM cells in vitro, inducing apotosis by activating caspase-3 in the intrinsic mitochondrial pathway and lysis of PARP, as well as reducing the expression of Bcl-2 and Bcl-XL proteins. Anticancer agent 201 can be used in cancer research.
    Anticancer agent 201
  • HY-P3148
    Astin B
    		Modulator
    Astin B is a orally active and potent cyclic pentapeptide, that can be isolated from Aster tataricus. Astin B has hepatotoxic effects in vitro and in vivo and that hepatic injury was primarily mediated by apoptosis in a mitochondria/caspase-dependent manner. Astin B induces autophagy in L-02 cells, increases LC3-II and decreases p62 expression.
    Astin B
  • HY-161732
    GQN-B37-E
    		Inhibitor
    GQN-B37-E is a potent selective binder and inhibitor of MCL-1. GQN-B37-E binds to the BH3-domain-binding pocket in MCL-1. GQN-B37-E exhibits binding affinity for MCL-1 at the submicromolar range (Ki = 0.6 μM) without apparent binding to BCL-2 or BCL-XL.
    GQN-B37-E
  • HY-170762A
    (+)-Mcl-1 inhibitor 21
    (+)-Mcl-1 inhibitor 21 (Example 1-37) is a Mcl-1 inhibitor with an IC50 of 172 nM. (+)-Mcl-1 inhibitor 21 exhibits proapototic and anti-proliferation activities against SUDHL5 and SUDHL10 cell lines and can be utilized in cancer research.
    (+)-Mcl-1 inhibitor 21
  • HY-168953
    Lysosomal P-gp targeted agent 1
    		Inhibitor
    Lysosomal P-gp targeted agent 1 (Compound 14) is an anti-tumor agent targeting lysosomal P-glycoprotein (Pgp). Lysosomal P-gp targeted agent 1 is selectively transported into lysosomes by overexpressed Pgp, release nitric oxide (NO) to generate reactive oxygen species (ROS), resulting in lysosomal membrane permeabilization (LMP) and inducing apoptosis. Lysosomal P-gp targeted agent 1 can overcome P-glycoprotein-mediated drug resistance and lead to cell cycle arrest, but relatively low toxicity to normal cells. Lysosomal P-gp targeted agent 1 has antitumor activity, significantly inhibits tumor volume.
    Lysosomal P-gp targeted agent 1
  • HY-RS01425
    Bcl2l10 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Bcl2l10 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Bcl2l10 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Bcl2l10 Mouse Pre-designed siRNA Set A
  • HY-131405
    β-Eleostearic acid
    		Inhibitor
    β-Eleostearic acid is an apoptosis inducer with antiproliferative properties. β-Eleostearic acid down-regulates and up-regulates the mRNA levels of Bcl-2 and Bax, respectively.
    β-Eleostearic acid
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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