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-147504
    Anticancer agent 63
    		Modulator
    Anticancer agent 63 (compound 3h) shows active in reducing the viability of different cancer cell lines, including SW480, HeLa, A549 and MCF-7, with IC50 values at 24 h of 4.9, 11.5, 9.4, and 3.4 μM, respectively. Anticancer agent 63 induce apoptosis in MCF-7 cells via down-regulating the expression of Bcl-2 and up-regulating the expression of IL-2 and Caspase-3. Anticancer agent 63 also shows antioxidant activity.
    Anticancer agent 63
  • HY-170763B
    (-)-Mcl-1 inhibitor 22
    (-)-Mcl-1 inhibitor 22 (compound 38) is an Mcl-1 inhibitor that works by blocking the interaction between Mcl-1 and pro-apoptotic proteins, reducing the anti-apoptotic activity of Mcl-1. (-)-Mcl-1 inhibitor 22 can be used in cancer research.
    (-)-Mcl-1 inhibitor 22
  • HY-P0300F
    Bak BH3 (72-87), TAMRA-labeled
    Bak BH3 (72-87), TAMRA-labeled is a biological active peptide.
    Bak BH3 (72-87), TAMRA-labeled
  • HY-RS01429
    Bcl2l11 Rat Pre-designed siRNA Set A
    		Inhibitor

    Bcl2l11 Rat Pre-designed siRNA Set A contains three designed siRNAs for Bcl2l11 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Bcl2l11 Rat Pre-designed siRNA Set A
    Bcl2l11 Rat Pre-designed siRNA Set A
  • HY-N2693
    6,8-Diprenylorobol
    		Modulator
    6,8-Diprenylorobol, a prenylated isoflavone, is a nature product that could be isolated from the leaves of Cudrania tricuspidata. 6,8-Diprenylorobol antiproliferative effect and induces apoptosis through activation of p53 and generation of ROS.
    6,8-Diprenylorobol
  • HY-N3913
    Furowanin A
    		Inhibitor
    Furowanin A is a flavonoid with anti-neoplastic effects. Furowanin A inhibits STAT3/Mcl-1 axis to suppress proliferation, block cell cycle progression, induce apoptosis and promote autophagy. Furowanin A potently inhibits colorectal cancer (CRC) cells.
    Furowanin A
  • HY-N0281R
    Daphnetin (Standard)
    		Inhibitor
    Daphnetin (Standard) is the analytical standard of Daphnetin. This product is intended for research and analytical applications. Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative can be found in plants of the Genus Daphne, is a potent, oral active protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively. Daphnetin triggers ROS-induced cell apoptosis and induces cytoprotective autophagy by modulating the AMPK/Akt/mTOR pathway. Daphnetin has anti-inflammation activitity and inhibits TNF-α, IL-1 , ROS, and MDA production. Daphnetin has schizontocidal activity against malaria parasites. Daphnetin can be used for rheumatoid arthritis , cancer and anti-malarian research.
    Daphnetin (Standard)
  • HY-N0087R
    Gambogic Acid (Standard)
    		Inhibitor
    Gambogic Acid (Standard) is the analytical standard of Gambogic Acid. This product is intended for research and analytical applications. Gambogic Acid (Beta-Guttiferrin) is derived from the gamboges resin of the tree Garcinia hanburyi. Gambogic Acid (Beta-Guttiferrin) inhibits Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 with IC50s of 1.47 μM, 1.21 μM, 2.02 μM, 0.66 μM, 1.06 μM and 0.79 μM.
    Gambogic Acid (Standard)
  • HY-149623
    Bcl-2-IN-13
    		Inhibitor
    Bcl-2-IN-13 is a Bcl-2 inhibitor with an IC50 value of 17 nM. Bcl-2-IN-13 can be used in cancer research.
    Bcl-2-IN-13
  • HY-N0361S
    Dihydrocapsaicin-d3
    		Modulator
    Dihydrocapsaicin-d3 is the deuterium labeled Dihydrocapsaicin (HY-N0361). Dihydrocapsaicin, a capsaicin, is a potent and selective TRPV1 (transient receptor potential vanilloid channel 1) agonist. Dihydrocapsaicin reduces AIF, Bax, and Caspase-3 expressions, and increased Bcl-2, Bcl-xL and p-Akt levels. Dihydrocapsaicin enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat.
    Dihydrocapsaicin-d<sub>3</sub>
  • HY-170763A
    (+)-Mcl-1 inhibitor 22
    (+)-Mcl-1 inhibitor 22 (Example 37) is a myeloid cell leukemia-1 (MCL-1) inhibitor which inhibits the antiapoptotoic activity of MCL-1 by inhibiting its interaction with proapototic proteins. (+)-Mcl-1 inhibitor 22 exhibits anti-proliferation activities against various cancer cell lines and can be utilized in cancer research.
    (+)-Mcl-1 inhibitor 22
  • HY-163764
    Bfl-1-IN-4
    		Inhibitor
    Bfl-1-IN-4 (Compound 8) is an inhibitor for Bcl-2 associated protein A1 (Bfl-1) with an IC50 of 16.8 μM.
    Bfl-1-IN-4
  • HY-P5342
    Hrk BH3
    Hrk BH3 is a biological active peptide. (BH3 domain of Hrk)
    Hrk BH3
  • HY-12048R
    Chelerythrine chloride (Standard)
    		Inhibitor
    Chelerythrine (chloride) (Standard) is the analytical standard of Chelerythrine (chloride). This product is intended for research and analytical applications. Chelerythrine chloride is a potent, cell-permeable inhibitor of protein kinase C, with an IC50 of 660 nM. Chelerythrine chloride inhibits the Bcl-XL-Bak BH3 peptide binding with IC50 of 1.5 μM and displaces Bax from Bcl-XL. Chelerythrine chloride induces apoptosis and autophagy.
    Chelerythrine chloride (Standard)
  • HY-13407R
    Gossypol (Standard)
    		Antagonist
    Gossypol (Standard) is the analytical standard of Gossypol. This product is intended for research and analytical applications. Gossypol 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 (Standard)
  • HY-120275
    CYD-2-11
    		Agonist
    CYD-2-11 is a selective Bax agonist with a Ki value of 34.1 nM. CYD-2-11 induces cell apoptosis and shows antiproliferative activity to breast cancer MDA-MB-231 and MCF-7 cell lines with IC50 values of 3.22 and 3.81 μM, respectively. CYD-2-11 suppresses tumor growth in MDA-MB-231 tumor models. CYD-2-11 can be used for the research of breast and lung cancer.
    CYD-2-11
  • HY-149625
    Bcl-2-IN-15
    		Inhibitor
    Bcl-2-IN-15 (Compound 13d)) is a Bcl-2 inhibitor (IC50: 363 nM). Bcl-2-IN-15 inhibits the proliferation ofNCI leukemia cancer cell line.
    Bcl-2-IN-15
  • HY-P10832
    ATWLPPRAANLLMAAS
    ATWLPPRAANLLMAAS is a chimeric peptide with anti-angiogenic and potent anti-tumor effects. ATWLPPRAANLLMAAS can inhibit the proliferation, viability, migration, and invasion of human hepatocellular carcinoma cells, and induce apoptosis..
    ATWLPPRAANLLMAAS
  • HY-163309
    Bcl-2-IN-19
    		Inhibitor
    Bcl-2-IN-19 (compound 27) is a potent Bcl-2 inhibitor for targeting breast cancer.
    Bcl-2-IN-19
  • HY-P1562A
    PUMA BH3 TFA
    		Activator
    PUMA BH3 TFA is a p53 upregulated modulator of apoptosis (PUMA) BH3 domain peptide, acts as a direct activator of Bak, with a Kd of 26 nM.
    PUMA BH3 TFA
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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