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Molecule Details

General Information of the Molecule
Name
Apoptosis regulator Bcl-xL (BCL-xL)
Synonyms
Bcl2like protein 1; Bcl2L1; Bcl2-L-1; Bcl-XL; Bcl-2-like protein 1; BCLX; BCL2L; Apoptosis regulator Bcl-X
Gene Name
BCL2L1
Gene ID
598
Sequence
MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLA
DSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAY
QSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEP
WIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
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Function
Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Potent inhibitor of cell death.
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Uniprot ID
B2CL1_HUMAN
TC Number
TC: 1.A.21.1.1
Pfam
PF00452 ; PF02180
KEGG ID
hsa598
TTD ID
T56510
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Pterostilbene   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + Vasostatin   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Carnosic acid   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gambogic acid   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Dasatinib   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gossypol   NP Info  + Imatinib   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Elemene   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Thalidomide   Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + ABT-737   Drug Info 
                    Structure +
                    Drug Combination 18 Down-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Flavopiridol   NP Info  + Bortezomib   Drug Info 
                    Structure +
                    Drug Combination 19 Down-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apigenin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 20 Down-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 21 Down-regulating the Expression of This Molecule [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 22 Down-regulating the Expression of This Molecule [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 23 Down-regulating the Expression of This Molecule [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ursolic acid   NP Info  + Capecitabine   Drug Info 
                    Structure +
                    Drug Combination 24 Down-regulating the Expression of This Molecule [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Bufalin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 25 Down-regulating the Expression of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Silibinin   NP Info  + Vorinostat   Drug Info 
                    Structure +
                    Drug Combination 26 Down-regulating the Expression of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 27 Down-regulating the Expression of This Molecule [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gossypol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 28 Down-regulating the Expression of This Molecule [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Terazosin   Drug Info 
                    Structure +
                    Drug Combination 29 Down-regulating the Expression of This Molecule [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Chlorogenic acid   NP Info  + Regorafenib   Drug Info 
                    Structure +
                    Drug Combination 30 Down-regulating the Expression of This Molecule [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 31 Down-regulating the Expression of This Molecule [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 32 Down-regulating the Expression of This Molecule [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 33 Down-regulating the Expression of This Molecule [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Vincristine   NP Info  + Vorinostat   Drug Info 
                    Structure +
                    Drug Combination 34 Down-regulating the Expression of This Molecule [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + BIBR1532   Drug Info 
                    Structure +
                    Drug Combination 35 Down-regulating the Expression of This Molecule [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Furanodiene + Curdione + Germacrone
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Furanodiene   NP Info     Drug Info 
Curdione   NP Info 
                    Drug Combination 36 Down-regulating the Expression of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Silibinin   NP Info  + Trichostatin A   Drug Info 
                    Structure +
                    Drug Combination 37 Down-regulating the Expression of This Molecule [36]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gambogic acid   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 38 Down-regulating the Expression of This Molecule [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Luteolin   NP Info  + SMC3   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [38]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [39]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Lonidamine   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Cucurbitacin D  NP Info  Investigative Cucurbitaceae
2 Cucurbitacin I  NP Info  Investigative Citrullus lanatus
Drug(s) of This Target
1 ABT-263  Drug Info  Phase 2 Chronic lymphocytic leukaemia
References
Reference 1 Pterostilbene Enhances TRAIL-Induced Apoptosis through the Induction of Death Receptors and Downregulation of Cell Survival Proteins in TRAIL-Resistance Triple Negative Breast Cancer Cells. J Agric Food Chem. 2017 Dec 27;65(51):11179-11191.
Reference 2 Herbal compound triptolide synergistically enhanced antitumor activity of vasostatin120-180. Anticancer Drugs. 2013 Oct;24(9):945-57.
Reference 3 Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif. 2011 Dec;44(6):591-601.
Reference 4 Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo. Biomed Pharmacother. 2017 May;89:827-837.
Reference 5 Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways. BMC Cell Biol. 2018 Dec 29;19(1):29.
Reference 6 Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells. Pediatr Neurosurg. 2000 Sep;33(3):123-31.
Reference 7 Suppression of NF-KappaB signaling and P-glycoprotein function by gambogic acid synergistically potentiates adriamycin -induced apoptosis in lung cancer. Curr Cancer Drug Targets. 2014;14(1):91-103.
Reference 8 Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008 Mar 27;27(14):2055-63.
Reference 9 Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 2011 Feb 15;128(4):951-61.
Reference 10 Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer. Dig Dis Sci. 2015 Apr;60(4):1067-80.
Reference 11 (-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007 Nov;48(11):2204-12.
Reference 12 Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells. Cancer Sci. 2017 Nov;108(11):2265-2272.
Reference 13 beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep. 2009 Jul;22(1):161-70.
Reference 14 Curcumin Combined with Thalidomide Reduces Expression of STAT3 and Bcl-xL, Leading to Apoptosis in Acute Myeloid Leukemia Cell Lines. Drug Des Devel Ther. 2020 Jan 15;14:185-194.
Reference 15 Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
Reference 16 Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010 Jul 15;127(2):257-68.
Reference 17 ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma cells in vitro and in vivo. J Int Med Res. 2012;40(4):1251-64.
Reference 18 Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood. 2004 Jul 15;104(2):509-18.
Reference 19 Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells. Evid Based Complement Alternat Med. 2011;2011:535172.
Reference 20 Resveratrol Enhances Chemosensitivity in Mouse Melanoma Model Through Connexin 43 Upregulation. Environ Toxicol. 2015 Jul 8;30(8):877-86.
Reference 21 Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-kappaB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33.
Reference 22 Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis. 2005 Nov;26(11):1905-13.
Reference 23 Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res. 2012 Sep 15;18(18):4942-53.
Reference 24 Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89.
Reference 25 Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells. Epigenetics. 2012 Oct;7(10):1161-72.
Reference 26 Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of DR5. Cancer Res. 2006 Feb 1;66(3):1740-50.
Reference 27 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786.
Reference 28 Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line. Cancer Lett. 2009 Apr 8;276(1):14-20.
Reference 29 Chlorogenic Acid Improves the Regorafenib Effects in Human Hepatocellular Carcinoma Cells. Int J Mol Sci. 2018 May 19;19(5):1518.
Reference 30 Resveratrol sensitizes androgen independent prostate cancer cells to death-receptor mediated apoptosis through multiple mechanisms. Prostate. 2007 Nov 1;67(15):1641-53.
Reference 31 Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013 Jan 8;18(1):701-20.
Reference 32 [Inhibitory effect of sorafenib combined with arsenic trioxide on hepatocellular carcinoma cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Apr;28(4):639-41.
Reference 33 The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. J Hematol Oncol. 2015 Jul 10;8:82.
Reference 34 Arsenic trioxide and BIBR1532 synergistically inhibit breast cancer cell proliferation through attenuation of NF-KappaB signaling pathway. Life Sci. 2020 Sep 15;257:118060.
Reference 35 Impact of fixed-dose combination of germacrone, curdione, and furanodiene on breast cancer cell proliferation. Cell J. Summer 2013;15(2):160-5.
Reference 36 Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings. Food Chem Toxicol. 2018 Sep;119:334-341.
Reference 37 Attenuating Smac mimetic compound 3-induced NF-kappaB activation by luteolin leads to synergistic cytotoxicity in cancer cells. J Cell Biochem. 2009 Dec 1;108(5):1125-31.
Reference 38 Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett. 2016 May;11(5):3527-3533.
Reference 39 Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation. Biochem Pharmacol. 2011 Dec 1;82(11):1619-29.
Reference 40 Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T-cell leukemia. Cancer. 2011 Jun 15;117(12):2735-46.
Reference 41 Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer-derived CD133-positive cells. Cancer. 2011 Jul 1;117(13):2970-85.
Reference 42 Clinical pipeline report, company report or official report of Roche (2009).
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China