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-162360
    EGFR-IN-109
    		Inhibitor
    EGFR-IN-109 (compound 4) is an EGFR inhibitor, with the IC50 values of 25.8 and 182.3 nM for EGFRWT and EGFRT790M, respectively. EGFR-IN-109 arrests the cancer cells’ growth at the G2/M phase and induces both early and late apoptosis. EGFR-IN-109 can be used in cancer research.
    EGFR-IN-109
  • HY-146253
    CDK1/2/4-IN-1
    		Activator
    CDK1/2/4-IN-1 (compound 3a) is a potent CDK inhibitor with IC50 values of 1.47, 0.78 and 0.87 μM for CDK1, CDK2 and CDK4, respectively. CDK1/2/4-IN-1 arrests cell cycle at G2/M phase and induces apoptosis. CDK1/2/4-IN-1 elevates Bax, caspase-3, P53 levels and decreases Bcl-2 level. CDK1/2/4-IN-1 can be used for cancer research.
    CDK1/2/4-IN-1
  • HY-111468
    Mcl1-IN-3
    		Inhibitor
    Mcl1-IN-3 is an inhibitor of Mcl1 extracted from patent WO2015153959A2, compound example 57; has an IC50 and Ki of 0.67 and 0.13 μM, respectively.
    Mcl1-IN-3
  • HY-175021
    HDAC-IN-91
    		Inhibitor
    HDAC-IN-91 is a multiple inhibitor of HDAC (IC50 = 134.22 nM for HDAC1, 66.29 nM for HDAC2), carbonic anhydrase (CA) (Ki = 72.03 nM for CA IX, 50.76 nM for XII), and tubulin polymerization ( IC50 = 2.56 μM). HDAC-IN-91 inhibits PARP1 and increases the Bax/Bcl-2 ratio. HDAC-IN-91 blocks the cell cycle at the G2/M phase and induces apoptosis through a mitochondrial apoptosis activation mechanism. HDAC-IN-91 can exert potent cytotoxic activity through tubulin polymerization inhibition. HDAC-IN-91 can be used in breast, colorectal, cervical and lung cancer research.
    HDAC-IN-91
  • HY-118341R
    Clitocine (Standard)
    		Inhibitor
    H-Chpro-OH.HCl (Standard) is the analytical standard of H-Chpro-OH.HCl. This product is intended for research and analytical applications. H-Chpro-OH.HCl is a proline derivative.
    Clitocine (Standard)
  • HY-175317
    Nogo-B-IN-1
    Nogo-B-IN-1 ((S,R)-4v) is a covalent Nogo-B inhibitor. Nogo-B-IN-1 inhibits the progression of osteosarcoma (OS) by suppressing Nogo-B activity and the PI3K/AKT/NF-κB/Bcl-2 signaling pathway. Nogo-B-IN-1 inhibits the proliferation of OS 143B cells (IC50 = 0.28 µM) and induces apoptosis. Nogo-B-IN-1 can be used for OS targeting research.
    Nogo-B-IN-1
  • HY-162780
    Mcl-1-IN-19
    		Inhibitor
    Mcl-1-IN-19 (compound 26) binds to Mcl-1, with the Ki of 86 pM. Mcl-1-IN-19 inhibits growth in H929 cells with the GI of 43 nM.
    Mcl-1-IN-19
  • HY-154961
    Mcl-1 inhibitor 14
    Mcl-1 inhibitor 14 (Compound (Ra)-10) is an inhibitor of myeloid cell leukemia-1 (MCL-1) with an Ki of 0.018 nM and can be used for anticancer research.
    Mcl-1 inhibitor 14
  • HY-170434
    Bfl-1-IN-6
    		Inhibitor
    Bfl-1-IN-6 (Compound 20) is an orally active inhibitor for Bcl-2 related protein A1 (BFL1) with an IC50 of 19 nM. Bfl-1-IN-6 stabilizes BFL1 protein, activates cleaved caspase 3, and exhibits antitumor efficacy in mouse models.
    Bfl-1-IN-6
  • HY-N10313
    Dehydrobruceine B
    		Modulator
    Dehydrobruceine B, a quassinoid, can be isolated from Brucea javanica. Dehydrobruceine B shows a synergistic effect with Cisplatin (HY-17394) to induce apoptosis via mitochondrial method. Dehydrobruceine B increases apoptosis-inducing factor (AIF) and Bax expression and suppresses Keap1-Nrf2.
    Dehydrobruceine B
  • HY-113427R
    trans-Vaccenic acid (Standard)
    		Inhibitor
    trans-Vaccenic acid (Standard) is the analytical standard of trans-Vaccenic acid (HY-113427). This product is intended for research and analytical applications. trans-Vaccenic acid is a naturally occurring trans fatty acid (TFA). trans-Vaccenic acid inhibits nasopharyngeal carcinoma (NPC) cell growth and induces apoptosis through the inhibition of Bad/Akt phosphorylation. trans-Vaccenic acid is a precursor for the synthesis of saturated fatty acid in the rumen and of conjugated Linoleic acid (CLA) at the tissue level. trans-Vaccenic acid exerts hypolipidemic effects in a rat model of obesity.
    trans-Vaccenic acid (Standard)
  • HY-162820
    Bcl-2-IN-21
    		Inhibitor
    Bcl-2-IN-21 (compound C1) is an iridium compound with anticancer activity that targets and inhibits Bcl-2. Bcl-2-IN-21 inhibits colony formation of cancer cells and induces elevated levels of Bax and caspase 3.
    Bcl-2-IN-21
  • HY-B0402R
    Amantadine (Standard)
    		Modulator
    Amantadine (Standard) is the analytical standard of Amantadine. This product is intended for research and analytical applications. Amantadine (1-Adamantanamine) is an orally avtive and potent antiviral agent with activity against influenza A viruses. Amantadine inhibits several ion channels such as NMDA and M2, and also inhibits Coronavirus ion channels. Amantadine also has anti-orthopoxvirus and anticancer activity. Amantadine can be used for Parkinson's disease, postoperative cognitive dysfunction (POCD) and COVID-19 research[4].
    Amantadine (Standard)
  • HY-P10614
    Bid BH3 peptide
    Bid BH3 peptide is a small peptide derived from Bid protein that can bind and activate the pro-apoptotic proteins Bax and Bak, leading to mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Bid BH3 peptide can be used to study mitochondrial bioenergetics.
    Bid BH3 peptide
  • HY-158328A
    CA IX/VEGFR-2-IN-2
    		Modulator
    CA IX/VEGFR-2-IN-2 (compound 5e) is a dual-targeted inhibitor. CA IX/VEGFR-2-IN-2 shows strong inhibitory effects on both CA IX (Ki=3.1 μM) and VEGFR-2 (IC50=32.1 nM). CA IX/VEGFR-2-IN-2 can be used for the study of pancreatic (PANC1), breast cancer (MCF7) and prostate cancer (PC3) .
    CA IX/VEGFR-2-IN-2
  • HY-147929
    Apoptotic agent-3
    		Activator
    Apoptotic agent-3 (compound 15f) promotes apoptosis through the potential mitochondria-mediated Bcl-2/Bax pathway and activation of the Caspase 3 pathway. Apoptotic agent-3 exhibits anti-proliferative activities and can be used for cancer research.
    Apoptotic agent-3
  • HY-P5325
    Bid BH3 (80-99)
    Bid BH3 (80-99) is a biological active peptide. (BID is a pro-apoptotic member of the 'BH3-only' (BOPS) subset of the BCL-2 family of proteins that constitute a critical control point in apoptosis. Bid is the first of the BOPs reported to bind and activate Bcl-2, Bax, and Bak. Bid serves as a death-inducing ligand that moves from the cytosol to the mitochondrial membrane to inactivate Bcl-2 or to activate Bax.Pyroglutamyl (pGlu) peptides may spontaneously form when either Glutamine (Q) or Glutamic acid (E) is located at the sequence N-terminus. The conversion of Q or E to pGlu is a natural occurrence and in general it is believed that the hydrophobic γ-lactam ring of pGlu may play a role in peptide stability against gastrointestinal proteases. Pyroglutamyl peptides are therefore considered a normal subset of such peptides and are included as part of the peptide purity during HPLC analysis.)
    Bid BH3 (80-99)
  • HY-P10386
    155H1
    		Inhibitor
    155H1 (Compound 11) is a stapled peptide, that covalently binds hMcl1 (172-323) with IC50 of 18 nM.
    155H1
  • HY-RS01428
    Bcl2l11 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Bcl2l11 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Bcl2l11 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Bcl2l11 Mouse Pre-designed siRNA Set A
  • HY-RS01419
    Bcl2a1 Rat Pre-designed siRNA Set A
    		Inhibitor

    Bcl2a1 Rat Pre-designed siRNA Set A contains three designed siRNAs for Bcl2a1 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Bcl2a1 Rat Pre-designed siRNA Set A
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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