Natural Product (NP) Details

General Information of the NP (ID: NP9654)
Name
Bufalin
Synonyms
3,14-Dihydroxy-bufa-20,22-dienolide; U549S98QLW; 5-((3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2H-pyran-2-one; CHEBI:517248; 3-beta,14-Dihydroxy-5-beta-bufa-20,22-dienolide; 3beta,14beta-dihydroxy-5beta-bufa-20,22-dienolide; 5-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one; Ch'an su; BUF; NSC 89595; BRN 5141601; (3beta,5beta)-3,14-dihydroxybufa-20,22-dienolide; 5beta, 20(22)-Bufadienolide-3beta, 14-diol; SCHEMBL165666; CHEMBL399680; DTXSID90873563; AMY40632; Bufalin: Bufa-20,22-dienolide, 3,14-dihydroxy-, (3b,5b)-,; HY-N0877; ZINC4215121; HSCI1_000110; LMST01130001; s7821; AKOS015965454; CS-3694; SMP2_000290; AC-20197; BS-17080; C16922; BRD-K63606607-001-01-8; BRD-K63606607-001-02-6; Q18379323; 5-beta-BUFA-20,22-DIENOLIDE, 3-beta,14-DIHYDROXY-; 5beta-Bufa-20,22-dienolide, 3beta,14-dihydroxy- (8CI); (3beta,5beta,10alpha,17alpha)-3,14-dihydroxybufa-20,22-dienolide; Bufa-20,22-dienolide, 3,14-dihydroxy-, (3-beta,5-beta)- (9CI); Bufa-20,22-dienolide, 3,14-dihydroxy-, (3beta,5beta)- (9CI)
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Species Origin Bufo gargarizans ...     Click to Show/Hide
Bufo gargarizans
Kingdom: Metazoa
Phylum: Chordata
Class: Amphibia
Order: Anura
Family: Bufonidae
Genus: Bufo
Species: Bufo gargarizans
Disease Breast cancer [ICD-11: 2C60] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.252
 
MDCK Permeability
 -5.084
 
PAMPA
 +
 
HIA
 - - -
 
Distribution
VDss
 -0.028
 
PPB
 96.9%
 
BBB
 - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 ++
CYP2B6 inhibitor
 +++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 ++
 
Excretion
CLplasma
 13.803
 
T1/2
 1.689
Toxicity
DILI
 - -
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 +++
 
Respiratory
 ++
 
Human Hepatotoxicity
 +
 
Ototoxicity
 - -
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 +
 
Hematotoxicity
 -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C24H34O4
PubChem CID
9547215
Canonical SMILES
CC12CCC(CC1CCC3C2CCC4(C3(CCC4C5=COC(=O)C=C5)O)C)O
InChI
1S/C24H34O4/c1-22-10-7-17(25)13-16(22)4-5-20-19(22)8-11-23(2)18(9-12-24(20,23)27)15-3-6-21(26)28-14-15/h3,6,14,16-20,25,27H,4-5,7-13H2,1-2H3/t16-,17+,18-,19+,20-,22+,23-,24+/m1/s1
InChIKey
QEEBRPGZBVVINN-BMPKRDENSA-N
CAS Number
CAS 465-21-4
Herb ID
HBIN018981
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          1,25-dihydroxyvitamin D3      Congenital alopecia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CYP24A1  Molecule Info 
Pathway MAP
Up-regulation Expression VDR  Molecule Info 
Pathway MAP
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Bufalin in combination with 1,25(OH)(2)D(3) enhanced the expression of VDR target genes, such as CYP24A1 and cathelicidin antimicrobial peptide, and effectively induced differentiation phenotypes.
          PD98059      Gastrointestinal stromal tumor     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model NB4 CVCL_0005 Acute promyelocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Bufalin synergized with PD98059 to inhibit the proliferation and induce the apoptosis of NB4 cells, which was associated with the downregulation of survivin expression and the upregulation of caspase-3 activation.
          Gefitinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MET  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of bufalin and gefitinib potently inhibited the growth of H1975 cells, and induced cell apoptosis. The potential mechanism for anti-tumor might be involved in blocking EGFR-PI3k/Akt pathway.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CBLB  Molecule Info 
Pathway MAP
Up-regulation Expression ERK1  Molecule Info 
Pathway MAP
Up-regulation Expression JNK1  Molecule Info 
Pathway MAP
Up-regulation Expression p38 beta  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells.
          Vorinostat      Mycosis fungoides     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors.
          MK2206      Nasopharyngeal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H929 CVCL_1600 Plasma cell myeloma Homo sapiens
U266B1 CVCL_0566 Plasma cell myeloma Homo sapiens
LP-1 CVCL_0012 Plasma cell myeloma Homo sapiens
RPMI-8226 CVCL_0014 Plasma cell myeloma Homo sapiens
                    Experimental
                    Result(s)		 MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model A total of 5x106 SMMC-7721 cells in 0.2 ml phosphate-buffered saline (PBS) were injected into the right flank of each mouse (six-week old male Balb/c nude mice) to form subcutaneous tumors.
                    Experimental
                    Result(s)		 Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
HLE CVCL_1281 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of cinobufacini and doxorubicin increases apoptosis of hepatocellular carcinoma cells through the Fas- and mitochondria-mediated pathways.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP3K5  Molecule Info 
Pathway MAP
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model To establish xenograft model, each mouse was subcutaneously injected with 6x106 Mia PaCa-2 cells in the back.
                    Experimental
                    Result(s)		 Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MKN45 CVCL_0434 Gastric adenocarcinoma Homo sapiens
BGC-823 CVCL_3360 Gastric cancer Homo sapiens
                    Experimental
                    Result(s)		 Bufalin reverses intrinsic and acquired drug resistance to cisplatin through the AKT signaling pathway in gastric cancer cells.
          Afatinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MET  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI1  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Bufalin reverses hepatocyte growth factor-induced resistance to afatinib in H1975 lung cancer cells.
          Osimertinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
                    In-vivo Model Male BALB/c nude mice (4-6 weeks old, 18-22 g) were injected subcutaneously in the rear flank with 4 * 106 PC-9OR cells.
                    Experimental
                    Result(s)		 Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.
Target and Pathway
Target(s) Epidermal growth factor receptor (EGFR)  Molecule Info 
Extracellular signal-regulated kinase 1 (ERK1)  Molecule Info  [15]
Extracellular signal-regulated kinase 2 (ERK2)  Molecule Info  [15]
Interferon-beta (IFNB1)  Molecule Info  [16]
NF-kappa-B-activating kinase (TBK1)  Molecule Info  [17]
Sodium pump subunit alpha-1 (ATP1A1)  Molecule Info  [18]
Stress-activated protein kinase JNK1 (JNK1)  Molecule Info  [19]
Stress-activated protein kinase JNK2 (JNK2)  Molecule Info  [19]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 cGMP-PKG signaling pathway
6 cAMP signaling pathway
7 Chemokine signaling pathway
8 HIF-1 signaling pathway
9 FoxO signaling pathway
10 Sphingolipid signaling pathway
11 Oocyte meiosis
12 mTOR signaling pathway
13 PI3K-Akt signaling pathway
14 Adrenergic signaling in cardiomyocytes
15 Vascular smooth muscle contraction
16 Dorso-ventral axis formation
17 TGF-beta signaling pathway
18 Axon guidance
19 VEGF signaling pathway
20 Osteoclast differentiation
21 Focal adhesion
22 Adherens junction
23 Gap junction
24 Signaling pathways regulating pluripotency of stem cells
25 Platelet activation
26 Toll-like receptor signaling pathway
27 NOD-like receptor signaling pathway
28 Natural killer cell mediated cytotoxicity
29 T cell receptor signaling pathway
30 B cell receptor signaling pathway
31 Fc epsilon RI signaling pathway
32 Fc gamma R-mediated phagocytosis
33 TNF signaling pathway
34 Circadian entrainment
35 Long-term potentiation
36 Neurotrophin signaling pathway
37 Retrograde endocannabinoid signaling
38 Glutamatergic synapse
39 Cholinergic synapse
40 Serotonergic synapse
41 Long-term depression
42 Regulation of actin cytoskeleton
43 Insulin signaling pathway
44 GnRH signaling pathway
45 Progesterone-mediated oocyte maturation
46 Estrogen signaling pathway
47 Melanogenesis
48 Prolactin signaling pathway
49 Thyroid hormone signaling pathway
50 Oxytocin signaling pathway
51 Type II diabetes mellitus
52 Aldosterone-regulated sodium reabsorption
53 Alzheimer's disease
54 Prion diseases
55 Alcoholism
56 Shigellosis
57 Salmonella infection
58 Pertussis
59 Leishmaniasis
60 Chagas disease (American trypanosomiasis)
61 Toxoplasmosis
62 Tuberculosis
63 Hepatitis C
64 Hepatitis B
65 Influenza A
66 Pathways in cancer
67 Viral carcinogenesis
68 Proteoglycans in cancer
69 Colorectal cancer
70 Renal cell carcinoma
71 Pancreatic cancer
72 Endometrial cancer
73 Glioma
74 Prostate cancer
75 Thyroid cancer
76 Melanoma
77 Bladder cancer
78 Chronic myeloid leukemia
79 Acute myeloid leukemia
80 Non-small cell lung cancer
81 Central carbon metabolism in cancer
82 Choline metabolism in cancer
83 Protein processing in endoplasmic reticulum
84 Wnt signaling pathway
85 RIG-I-like receptor signaling pathway
86 Dopaminergic synapse
87 Inflammatory mediator regulation of TRP channels
88 Adipocytokine signaling pathway
89 Non-alcoholic fatty liver disease (NAFLD)
90 Epithelial cell signaling in Helicobacter pylori infection
91 HTLV-I infection
92 Herpes simplex infection
93 Epstein-Barr virus infection
94 Cytokine-cytokine receptor interaction
95 Cytosolic DNA-sensing pathway
96 Jak-STAT signaling pathway
97 Measles
98 MicroRNAs in cancer
99 Cardiac muscle contraction
100 Insulin secretion
101 Thyroid hormone synthesis
102 Endocrine and other factor-regulated calcium reabsorption
103 Proximal tubule bicarbonate reclamation
104 Salivary secretion
105 Gastric acid secretion
106 Pancreatic secretion
107 Carbohydrate digestion and absorption
108 Protein digestion and absorption
109 Bile secretion
110 Mineral absorption
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 TNFalpha Signaling Pathway
4 IL2 Signaling Pathway
Panther Pathway Alzheimer disease-amyloid secretase pathway Click to Show/Hide
2 Angiogenesis
3 Apoptosis signaling pathway
4 B cell activation
5 EGF receptor signaling pathway
6 Endothelin signaling pathway
7 FGF signaling pathway
8 Inflammation mediated by chemokine and cytokine signaling pathway
9 Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade
10 Integrin signalling pathway
11 Interferon-gamma signaling pathway
12 Interleukin signaling pathway
13 PDGF signaling pathway
14 Parkinson disease
15 TGF-beta signaling pathway
16 T cell activation
17 Toll receptor signaling pathway
18 VEGF signaling pathway
19 Ras Pathway
20 Angiotensin II-stimulated signaling through G proteins and beta-arrestin
21 CCKR signaling map ST
22 FAS signaling pathway
23 Oxidative stress response
24 Huntington disease
Pathwhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine Click to Show/Hide
2 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
3 Fc Epsilon Receptor I Signaling in Mast Cells
4 Insulin Signalling
5 Kidney Function
6 Lactose Degradation
7 Trehalose Degradation
8 Muscle/Heart Contraction
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells Click to Show/Hide
2 Endothelins
3 BCR signaling pathway
4 Signaling events mediated by PRL
5 ErbB4 signaling events
6 GMCSF-mediated signaling events
7 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
8 S1P3 pathway
9 EPHB forward signaling
10 Osteopontin-mediated events
11 S1P4 pathway
12 Presenilin action in Notch and Wnt signaling
13 TRAIL signaling pathway
14 CDC42 signaling events
15 Signaling events regulated by Ret tyrosine kinase
16 Angiopoietin receptor Tie2-mediated signaling
17 S1P1 pathway
18 Regulation of Telomerase
19 Netrin-mediated signaling events
20 Role of Calcineurin-dependent NFAT signaling in lymphocytes
21 Glucocorticoid receptor regulatory network
22 Arf6 downstream pathway
23 mTOR signaling pathway
24 IL2-mediated signaling events
25 EGF receptor (ErbB1) signaling pathway
26 Ras signaling in the CD4+ TCR pathway
27 Ceramide signaling pathway
28 Integrins in angiogenesis
29 IFN-gamma pathway
30 ErbB1 downstream signaling
31 ATF-2 transcription factor network
32 ErbB2/ErbB3 signaling events
33 ALK1 signaling events
34 PDGFR-beta signaling pathway
35 Neurotrophic factor-mediated Trk receptor signaling
36 Syndecan-1-mediated signaling events
37 Retinoic acid receptors-mediated signaling
38 Nongenotropic Androgen signaling
39 CXCR3-mediated signaling events
40 VEGFR1 specific signals
41 Regulation of cytoplasmic and nuclear SMAD2/3 signaling
42 Signaling events mediated by Stem cell factor receptor (c-Kit)
43 Signaling events mediated by VEGFR1 and VEGFR2
44 Syndecan-2-mediated signaling events
45 Cellular roles of Anthrax toxin
46 S1P2 pathway
47 Trk receptor signaling mediated by the MAPK pathway
48 Downstream signaling in na&#xef
49
50 VEGFR3 signaling in lymphatic endothelium
51 Alpha-synuclein signaling
52 FGF signaling pathway
53 RhoA signaling pathway
54 Noncanonical Wnt signaling pathway
55 CD40/CD40L signaling
56 Reelin signaling pathway
57 FAS (CD95) signaling pathway
58 IL1-mediated signaling events
59 Rapid glucocorticoid signaling
60 FoxO family signaling
61 Regulation of Androgen receptor activity
62 p75(NTR)-mediated signaling
63 JNK signaling in the CD4+ TCR pathway
64 Nephrin/Neph1 signaling in the kidney podocyte
65 HIV-1 Nef: Negative effector of Fas and TNF-alpha
66 EPO signaling pathway
67 Ephrin B reverse signaling
68 p53 pathway
69 N-cadherin signaling events
70 RAC1 signaling pathway
71 Signaling events mediated by focal adhesion kinase
72 Glypican 3 network
73 IL12 signaling mediated by STAT4
74 Regulation of nuclear SMAD2/3 signaling
75 Class IB PI3K non-lipid kinase events
76 BMP receptor signaling
77 Regulation of retinoblastoma protein
Reactome MAPK3 (ERK1) activation Click to Show/Hide
2 RAF-independent MAPK1/3 activation
3 ISG15 antiviral mechanism
4 ERK/MAPK targets
5 Regulation of actin dynamics for phagocytic cup formation
6 Oxidative Stress Induced Senescence
7 Senescence-Associated Secretory Phenotype (SASP)
8 Oncogene Induced Senescence
9 FCERI mediated MAPK activation
10 Regulation of HSF1-mediated heat shock response
11 NCAM signaling for neurite out-growth
12 Activation of the AP-1 family of transcription factors
13 Thrombin signalling through proteinase activated receptors (PARs)
14 Negative regulation of FGFR1 signaling
15 Negative regulation of FGFR2 signaling
16 Negative regulation of FGFR3 signaling
17 Negative regulation of FGFR4 signaling
18 RHO GTPases Activate WASPs and WAVEs
19 RAF/MAP kinase cascade
20 MAP2K and MAPK activation
21 Negative feedback regulation of MAPK pathway
22 Negative regulation of MAPK pathway
23 Signal attenuation
24 Advanced glycosylation endproduct receptor signaling
25 Gastrin-CREB signalling pathway via PKC and MAPK
26 Growth hormone receptor signaling
27 NRAGE signals death through JNK
28 NRIF signals cell death from the nucleus
29 DSCAM interactions
30 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
31 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
32 Interferon alpha/beta signaling
33 Regulation of IFNA signaling
34 TRAF3-dependent IRF activation pathway
35 TRAF6 mediated IRF7 activation
36 Factors involved in megakaryocyte development and platelet production
37 MAPK1 (ERK2) activation
38 Golgi Cisternae Pericentriolar Stack Reorganization
39 Recycling pathway of L1
40 CREB phosphorylation through the activation of Ras
41 Ion transport by P-type ATPases
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 Serotonin Receptor 4/6/7 and NR3C Signaling
3 Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
4 Serotonin HTR1 Group and FOS Pathway
5 TCR Signaling Pathway
6 Hypothetical Network for Drug Addiction
7 EPO Receptor Signaling
8 TGF Beta Signaling Pathway
9 Regulation of Actin Cytoskeleton
10 IL-2 Signaling Pathway
11 Insulin Signaling
12 MAPK Cascade
13 IL-4 Signaling Pathway
14 MAPK Signaling Pathway
15 IL-6 signaling pathway
16 Signaling of Hepatocyte Growth Factor Receptor
17 Kit receptor signaling pathway
18 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
19 IL-3 Signaling Pathway
20 Cardiac Hypertrophic Response
21 MAP kinase activation in TLR cascade
22 Fc epsilon receptor (FCERI) signaling
23 RAF/MAP kinase cascade
24 Structural Pathway of Interleukin 1 (IL-1)
25 Genes and (Common) Pathways Underlying Drug Addiction
26 Signal Transduction of S1P Receptor
27 PDGF Pathway
28 Alpha 6 Beta 4 signaling pathway
29 Spinal Cord Injury
30 BDNF signaling pathway
31 Integrated Pancreatic Cancer Pathway
32 Oncostatin M Signaling Pathway
33 Corticotropin-releasing hormone
34 Interleukin-11 Signaling Pathway
35 AGE/RAGE pathway
36 TNF alpha Signaling Pathway
37 Prostate Cancer
38 Signaling Pathways in Glioblastoma
39 TSLP Signaling Pathway
40 IL-9 Signaling Pathway
41 IL17 signaling pathway
42 Alzheimers Disease
43 IL-7 Signaling Pathway
44 TWEAK Signaling Pathway
45 FSH signaling pathway
46 Leptin signaling pathway
47 RANKL/RANK Signaling Pathway
48 IL-1 signaling pathway
49 Thrombin signalling through proteinase activated receptors (PARs)
50 Signaling by Insulin receptor
51 Signaling by FGFR
52 RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
53 L1CAM interactions
54 Advanced glycosylation endproduct receptor signaling
55 Apoptosis Modulation and Signaling
56 MicroRNAs in cardiomyocyte hypertrophy
57 Regulation of toll-like receptor signaling pathway
58 Osteopontin Signaling
59 IL-5 Signaling Pathway
60 DNA Damage Response (only ATM dependent)
61 ErbB Signaling Pathway
62 EGF/EGFR Signaling Pathway
63 TGF beta Signaling Pathway
64 FAS pathway and Stress induction of HSP regulation
65 Transcriptional activation by NRF2
66 NLR Proteins
67 Nanoparticle-mediated activation of receptor signaling
68 EBV LMP1 signaling
69 JAK/STAT
70 Nanoparticle triggered regulated necrosis
71 B Cell Receptor Signaling Pathway
72 Signalling by NGF
73 Intrinsic Pathway for Apoptosis
74 DSCAM interactions
75 Type II diabetes mellitus
76 Physiological and Pathological Hypertrophy of the Heart
77 Osteoclast Signaling
78 Type II interferon signaling (IFNG)
79 Senescence and Autophagy in Cancer
80 Cytokines and Inflammatory Response
81 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
82 Interferon alpha/beta signaling
83 Vitamin A and Carotenoid Metabolism
84 Apoptosis-related network due to altered Notch3 in ovarian cancer
85 Bladder Cancer
86 Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
87 Nifedipine Activity
88 Aryl Hydrocarbon Receptor
89 Endothelin Pathways
90 Integrated Breast Cancer Pathway
91 Opioid Signalling
92 Integrin-mediated Cell Adhesion
93 Heart Development
94 Angiogenesis
95 Wnt Signaling Pathway
96 Wnt Signaling Pathway and Pluripotency
97 ATM Signaling Pathway
98 Iron uptake and transport
References
Reference 1 Bufalin inhibits human breast cancer tumorigenesis by inducing cell death through the ROS-mediated RIP1/RIP3/PARP-1 pathways. Carcinogenesis. 2018 May 3;39(5):700-707.
Reference 2 Increased nuclear expression and transactivation of vitamin D receptor by the cardiotonic steroid bufalin in human myeloid leukemia cells. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):144-51.
Reference 3 Bufalin induces the apoptosis of acute promyelocytic leukemia cells via the downregulation of survivin expression. Acta Haematol. 2012;128(3):144-50.
Reference 4 [Effect of bufalin combined gefitinib on lung cancer H1975 cells and its mechanisms research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Aug;33(8):1081-5.
Reference 5 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 6 Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors. Biochem Biophys Res Commun. 2016 Sep 9;478(1):227-233.
Reference 7 MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway. Cell Death Dis. 2017 May 11;8(5):e2776.
Reference 8 Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling. Int J Oncol. 2018 Jun;52(6):2051-2060.
Reference 9 Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncol Lett. 2018 May;15(5):8019-8026.
Reference 10 Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways. Am J Chin Med. 2017;45(7):1537-1556.
Reference 11 Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer. Oncol Lett. 2012 Oct;4(4):792-798.
Reference 12 Bufalin reverses intrinsic and acquired drug resistance to cisplatin through the AKT signaling pathway in gastric cancer cells. Mol Med Rep. 2016 Aug;14(2):1817-22.
Reference 13 [Bufalin reverses hepatocyte growth factor-induced resistance to afatinib in H1975 lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2015 Jul;37(7):490-6.
Reference 14 Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer. Toxicol Appl Pharmacol. 2019 Sep 15;379:114662.
Reference 15 Inhibitory effect of bufalin and cinobufagin on steroidogenesis via the activation of ERK in human adrenocortical cells. Br J Pharmacol. 2012 Mar;165(6):1868-1876.
Reference 16 Cardiac glycosides are potent inhibitors of interferon-Beta gene expression. Nat Chem Biol. 2011 Jan;7(1):25-33.
Reference 17 Bufalin Suppresses Migration and Invasion of Hepatocellular Carcinoma Cells Elicited by Poly (I:C) Therapy. Oncoimmunology. 2018 Feb 8;7(5):e1426434.
Reference 18 The sodium pump Alpha1 subunit regulates bufalin sensitivity of human glioblastoma cells through the p53 signaling pathway. Cell Biol Toxicol. 2019 Dec;35(6):521-539.
Reference 19 Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med. 2011 Oct 1;51(7):1365-75.
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