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-181074
    Tubulin polymerization-IN-88
    		Inhibitor
    Tubulin polymerization-IN-88 is a tubulin inhibitor that blocks tubulin polymerization, leading to microtubule destabilization and disruption of the mitotic spindle. Tubulin polymerization-IN-88 induces G2/M phase arrest and apoptosis in cancer cells, and inhibits cancer cell migration and self-renewal of cancer stem cells. It exhibits in vitro anti-proliferative activity against cancer cells with selectivity over normal cells. Tubulin polymerization-IN-88 also demonstrates in vivo anti-cancer activity without significant toxicity. Tubulin polymerization-IN-88 is applicable for research on glioblastoma, lung cancer, endometrial cancer, ovarian cancer, and leukemia.
    Tubulin polymerization-IN-88
  • HY-179439
    Multi-kinase-IN-8
    		Inhibitor
    Multi-kinase-IN-8 is a muti-kinase inhibitor. Multi-kinase-IN-8 inhibits COX-1 (IC50 of 12.6 μM), COX-2 (IC50 of 0.05 μM) and VEGFR-2 (IC50 of 0.12 nM). Multi-kinase-IN-8 inhibits tumor-associated carbonic anhydrases (CA IX and CA XII with Ki of 31.5 nM and 386.9 nM, respectively). Multi-kinase-IN-8 triggers cell cycle arrest and apoptosis through upregulation of Caspase 9 and Bax along with downregulation of Bcl 2. Multi-kinase-IN-8 suppresses PGE2, p-VEGFR-2, MMP-9 and HIF-1α and exhibits growth-inhibitory activity against breast cancer, lung cancer, and colorectal adenocarcinoma.
    Multi-kinase-IN-8
  • HY-146105
    Anticancer agent 65
    		Modulator
    Anticancer agent 65 (compound 4c) shows excellent activity in cancer cell lines, especially A549 cells, with an IC50 of 1.07 μM. Anticancer agent 65 induces S-phase arrest in A549 cells and increases the expression level of p53 and p21. Anticancer agent 65 causes apoptosis, ROS generation and collapse of MMP in A549 cells.
    Anticancer agent 65
  • HY-N1423AR
    Glycocholic acid sodium (Standard)
    		Modulator
    Glycocholic acid (sodium) (Standard) is the analytical standard of Glycocholic acid sodium (HY-N1423A). This product is intended for research and analytical applications. Glycocholic acid sodium is a bile acid derivative. Glycocholic acid downregulates MDR1, Bcl-2, MRP1, MRP2 and FXR, upregulates Bax, p53, caspase-9, caspase-3, TGR5 and S1PR2. Glycocholic acid sodium inhibits multidrug resistance and efflux pumps, induces mitochondrial apoptosis, and enhances chemosensitivity. Glycocholic acid sodium modulates related bile acid receptor signaling. Glycocholic acid sodium suppresses growth and conjugation of Enterobacteriaceae and increases their antibiotic susceptibility. Glycocholic acid sodium can be used for the research of colon adenocarcinoma and cholangiocarcinoma (CCA).
    Glycocholic acid sodium (Standard)
  • HY-179052
    Apoptosis inducer 50
    		Activator
    Apoptosis inducer 50 (Compound 5e) is an apoptosis inducer as well as an autophagy inducer agent. Apoptosis inducer 50 exhibits potent and selective anti-cancer activity against triple-negative breast cancer cells and metastatic colon cancer cells. Apoptosis inducer 50 upregulates the expression of pro-apoptotic proteins (Bax, Bim, cleaved Caspase-9) and downregulates the expression of the anti-apoptotic protein (BCL-XL). Apoptosis inducer 50 upregulates key autophagy markers such as Beclin-1 and ATG5, and enhances the conversion of LC3-I to LC3-II., Apoptosis inducer 50 arrests cancer cells in the G1/S phase by upregulating the expression of p21 and p27 while downregulating Cyclin D1. Apoptosis inducer 50 increases the level of ROS.
    Apoptosis inducer 50
  • HY-117585
    Caylin-2
    		Inhibitor 99.0%
    Caylin-2 is a Bcl-XL binder and analog of Nutlin-3 (HY-50696). Caylin-2 interacts with the hydrophobic groove of Bcl-XL, with binding diminished by steric collision from its trifluoromethyl groups. Caylin-2 can be used for cancer research.
    Caylin-2
  • HY-175531
    EGFR-IN-169
    EGFR-IN-169 is an epidermal growth factor (EGFR) (IC50 = 5.19 μM) inhibitor form panaxadiol. EGFR-IN-169 interferes with the migration and growth of colorectal cancer cells by inhibiting EGFR-mediated RalA/EMT pathway. EGFR-IN-169 shows an IC50 value of 4.46 μM and SI of 16.92 for HCT-116 cells. EGFR-IN-169 inhibits CDKs activity, induces G0/G1 cycle arrest and inhibits migration and invasion. EGFR-IN-169 reduces mitochondrial membrane potential and induces apoptosis and ROS production. EGFR-IN-169 can be used for the research of cancer, such as colorectal cancer.
    EGFR-IN-169
  • HY-178104
    HDAC-IN-93
    		Inhibitor
    HDAC-IN-93 is a HDAC inhibitor with promising total pan-HDAC inhibitory activity. HDAC-IN-93 demonstrates significant broad-spectrum antiproliferative activity across various cancer cell lines. HDAC-IN-93 induces cell apoptosis along with necrosis. HDAC-IN-93 can be used for the studies of prostate cancer and breast cancer.
    HDAC-IN-93
  • HY-174338
    GPER/Bcl-2-IN-1
    		Inhibitor
    GPER/Bcl-2-IN-1 is a GPER/Bcl-2 inhibitor. GPER/Bcl-2-IN-1 can inhibit the proliferation and neurospheres formation of glioblastoma cells. GPER/Bcl-2-IN-1 can be used for the study of glioblastoma multiforme (GBM).
    GPER/Bcl-2-IN-1
  • HY-181093
    EGFR-IN-191
    		Modulator
    EGFR-IN-191 is an anti-tumor agent targeting both EGFR and AKT. EGFR-IN-191 exerts its anti-tumor activity by inducing DNA damage, apoptosis, cell cycle arrest, and inhibition of the PI3K/AKT-EGFR signaling pathway in tumor cells. EGFR-IN-191 can be used in the study of tumors such as triple-negative breast cancer.
    EGFR-IN-191
  • HY-RS01427
    BCL2L11 Human Pre-designed siRNA Set A
    		Inhibitor

    BCL2L11 Human Pre-designed siRNA Set A contains three designed siRNAs for BCL2L11 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    BCL2L11 Human Pre-designed siRNA Set A
  • 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-176283
    Tubulin/LSD1-IN-1
    		Inhibitor
    Tubulin/LSD1-IN-1 is an effective dual inhibitor of Tubulin polymerization and LSD1 (IC50 = 1.72 μM). Tubulin/LSD1-IN-1 has broad-spectrum antiproliferative activity against cancer cell lines. Tubulin/LSD1-IN-1 inhibits tubulin polymerization by targeting colchicine binding sites, thereby disrupting the microtubule network in gastric cancer cells. Tubulin/LSD1-IN-1 increases the methylation levels of H3K4me1/2 and H3K9me2/3, thereby achieving epigenetic regulation. Tubulin/LSD1-IN-1 induces G2/M arrest, promotes apoptosis, and effectively inhibits colony formation of gastric cancer cells.
    Tubulin/LSD1-IN-1
  • 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
  • HY-181098
    FKA-9i
    		Inhibitor
    FKA-9i is an orally active anticancer agent. FKA-9i directly binds to and promotes the degradation of oncoproteins LRPPRC (kd: 7.387 μM), YBX1 (kd: 16.52 μM) and RPN1 (kd: 26.82 μM). FKA-9i inhibits the MAPK signaling pathway and mitochondrial oxidative phosphorylation. FKA-9i also induces cancer cell cycle arrest, apoptosis, mitochondrial dysfunction and ROS accumulation. FKA-9i can be used in the research of tumors such as gastric cancer.
    FKA-9i
  • 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-181060
    Apoptosis inducer 56
    		Modulator
    Apoptosis inducer 56 is an apoptosis inducer. Apoptosis inducer 56 induces DNA damage (upregulation of γH2AX and p-ATM expression) by minor groove binding. Apoptosis inducer 56 induces intrinsic apoptosis (upregulation of p53 and Bax/Bcl-2 ratio, cleaved caspase-7) via S-phase cell cycle arrest. Apoptosis inducer 56 shows selectivity for cancer cells over normal breast epithelial cells. Apoptosis inducer 56 can be used for the research of breast cancer.
    Apoptosis inducer 56
  • 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)
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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