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-134008
    Protoapigenone
    		Inducer 99.84%
    Protoapigenone is an antineoplastic agent isolated from ferns. Protoapigenone has significant inhibitory activity against Hep G2, Hep 3B, MCF-7, A549 and MDAMB-231, with IC50s values of 1.60, 0.23, 0.78, 3.88 and 0.27 μg/mL respectively.
    Protoapigenone
  • HY-129702
    MCL-1/BCL-2-IN-4
    		Inhibitor 99.95%
    MCL-1/BCL-2-IN-4 (Compound 7) is a potent and selective Mcl-1 and Bcl-2 dual inhibitor.
    MCL-1/BCL-2-IN-4
  • HY-12826
    IMB-XH1
    		Inhibitor ≥98.0%
    IMB-XH1 is an inhibitor of myeloid cell factor 1 (Mcl-1). IMB-XH1 is a non-competitive Delhi metallo-β-lactamase (NDM-1) inhibitor. The IC50s of IMB-XH1 against metallo-β-lactamases NDM-1, IMP-4, ImiS and L1 are 0.4637 μM, 3.980 μM, 0.2287 μM and 1.158 μM, respectively.
    IMB-XH1
  • HY-170380
    XY221
    		Inhibitor
    XY221 (Compound 16o) selectively inhibits BRD4 BD2, with an IC50 of 5.8 nM. XY221 demonstrates high pan-BD2 selectivity (667-fold over BRD4 BD1) and BRD4 BD2 domain selectivity (9−32-fold over BRD2/3/T BD2). XY221 induce Apoptosis in MV4-11 cells and shows anticancer activity .
    XY221
  • HY-13408
    (+)-Apogossypol
    		Inhibitor
    (+)-Apogossypol is a pan-BCL-2 antagonist. (+)-Apogossypol binds to Mcl-1, Bcl-2 and Bcl-xL with EC50s of 2.6, 2.8 and 3.69 µM, respectively.
    (+)-Apogossypol
  • HY-147889
    BBR-BODIPY
    		Activator 98.15%
    BBR-BODIPY is a fluorescent probe that allows screening its interaction with the targeted cells. BBR-BODIPY induces apoptosis and changes the expression of apoptosis-related proteins.
    BBR-BODIPY
  • HY-N5033
    17-Hydroxy sprengerinin C
    		Activator 99.68%
    17-Hydroxy sprengerinin C (compound 10) is a glycoside compound isolated from rhizomes of Polygonatum sibiricum. 17-Hydroxy sprengerinin C possesses stronger anticancer activities. 17-Hydroxy sprengerinin C reduces the expression of Blc-2 and pro-caspase3 and increases the production of Bax.
    17-Hydroxy sprengerinin C
  • HY-125847
    Salvianolic acid F
    		99.72%
    Salvianolic acid F is a KRAS inhibitor. Salvianolic acid F inhibits cancer cell growth, invasion, and migration and induces apoptosis via the EP300/PI3K/AKT pathway in vitro. Salvianolic acid F inhibits the growth of KRAS-dependent lung cancer cells via the PI3K/AKT signaling pathway in vivo. Salvianolic acid F can be used in the research of various cancers, including lung and ovarian cancer.
    Salvianolic acid F
  • HY-N0867
    13-Oxyingenol-13-dodecanoate
    		Inhibitor 99.37%
    13-Oxyingenol-dodecanoate (13OD) is a tumor suppressor agent. 13-Oxyingenol-dodecanoate has anti-HIV-1 activity with EC50 value of 33.7 nM.13-Oxyingenol-dodecanoate can induce the expression of ULK1 to effect mitochondrial dysfunction and cellular autophagy. 13-Oxyingenol-dodecanoate also increases the expression of BAX and suppresses the expression of BCL-2 to effect apoptosis.
    13-Oxyingenol-13-dodecanoate
  • HY-129159
    (-)-Clerosterol
    (-)-Clerosterol is a natural product that can be isolated from Codium fragile.
    (-)-Clerosterol
  • HY-N9802
    n-Butyl-β-D-fructofuranoside
    		Activator
    n-Butyl-β-D-fructofuranoside could be isolated from kangaisan. n-Butyl-β-D-fructofuranoside induces apoptosis through the mitochondrial pathway. n-Butyl-β-D-fructofuranoside can be used for cancer research.
    n-Butyl-β-D-fructofuranoside
  • HY-129179B
    (Rac)-Lisaftoclax
    		Inhibitor 98.22%
    (Rac)-Lisaftoclax ((Rac)-APG-2575) is a Bcl-2 inhibitor that can be uesd for hematologic malignancy research (CN112898295A).
    (Rac)-Lisaftoclax
  • HY-161410
    WH244
    		Degrader 99.82%
    WH244 is a second generation BCL-2 and BCL-xL dual depressant (PROTAC). The primary activity of WH244 is the specific degradation of BCL-2 and BCL-xL proteins (BCL-xL: DC50=0.6 nM, BCL-2: DC50=7.4 nM). WH244 promotes their ubiquitination and subsequent proteasome degradation by targeting these proteins, thereby restoring the cell's apoptosis pathway. WH244 has good antitumor activity. (Pink: BCL-2/BCL-xL ligand (HY-161415); Blue: E3 ligase ligand (HY-112078); Black: linker).
    WH244
  • HY-160108
    Bcl-2-IN-17
    		Inhibitor
    Bcl-2-IN-17 is a Bcl2 inhibitor and can be used for the research of diseases associated with Bcl anti-apoptotic protein.
    Bcl-2-IN-17
  • HY-101083
    BDA-366
    		Antagonist
    BDA-366 is a potent Bcl2 antagonist (Ki = 3.3 nM), binding Bcl2-BH4 domain with high affinity and selectivity. BDA-366 induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer cells.
    BDA-366
  • HY-161242
    CBI1
    		Inhibitor
    CBI1 is a covalent BAX inhibitor. CBI1 selectively derivatizes BAX at C126 and inhibits BAX activation by triggering ligands or point mutagenesis. CBI1 blocks t-2-hex lipidation and oligomerization of BAX. CBI1 inhibits BAX activation induced by BH3 ligands, F116A mutagenesis or t-2-hex.
    CBI1
  • HY-146548
    Anticancer agent 43
    		Inducer 98.58%
    Anticancer Agent 43 is a potent anticancer agent. Anticancer Agent 43 induces apoptosis by caspase 3, PARP1, and Bax dependent mechanisms. Anticancer Agent 43 induces DNA damage.
    Anticancer agent 43
  • HY-B1971R
    Deltamethrin (Standard)
    Deltamethrin (Standard) is the analytical standard of Deltamethrin. This product is intended for research and analytical applications. 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 (Standard)
  • HY-115718A
    PZ703b TFA
    		Degrader 98.62%
    PZ703b TFA is a Bcl-xl PROTAC degradation agent that induces apoptosis and inhibits cancer cell proliferation for bladder cancer research.
    PZ703b TFA
  • HY-161659
    Apoptosis inducer 19
    		Modulator 98.31%
    Apoptosis inducer 19 (Compound 7g) is an Apoptosis inducer. Apoptosis inducer 19 elevates expression of pro-apoptotic proteins (Bax and caspase-3) and downregulates anti-apoptotic protein (Bcl-2). Apoptosis inducer 19 upregulates cellular reactive oxygen species (ROS) levels and disrupts mitochondrial membrane potential (MMP). Apoptosis inducer 19 can be used for triple-negative breast cancer (TNBC) research.
    Apoptosis inducer 19
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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