Natural Product (NP) Details

General Information of the NP (ID: NP6128)
Name
Gossypol
Synonyms
(-)-Gossypol; 90141-22-3; (+)-Gossypol; Pogosin; Tash 1; racemic-Gossypol; (R)-(-)-Gossypol; (R)-Gossypol; (+-)-Gossypol; (+/-)-Gossypol; CCRIS 2689; NSC56817; NSC 56817; NSC 624336; BRN 1917878; CHEMBL51483; AI3-22957; 20300-26-9; 1,1',6,6',7,7'-Hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalene]-8,8'-dicarbaldehyde; 2,2'-bi[8-Formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene]; 2,2'-Bis(1,6,7-trihydroxy-3-methyl-5-isopropyl-8-aldehydonaphthalene); NSC624336; Gossypol acetate
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Species Origin Gossypium herbaceum ...     Click to Show/Hide
Gossypium herbaceum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malvales
Family: Malvaceae
Genus: Gossypium
Species: Gossypium herbaceum
Disease Prostate cancer [ICD-11: 2C82] Phase 2 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.282
 
MDCK Permeability
 -4.805
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 -0.003
 
PPB
 98.1%
 
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
 8.325
 
T1/2
 1.829
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
C30H30O8
PubChem CID
3503
Canonical SMILES
CC1=CC2=C(C(=C(C(=C2C(C)C)O)O)C=O)C(=C1C3=C(C4=C(C=C3C)C(=C(C(=C4C=O)O)O)C(C)C)O)O
InChI
1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3
InChIKey
QBKSWRVVCFFDOT-UHFFFAOYSA-N
CAS Number
CAS 20300-26-9
Herb ID
HBIN028351
SymMap ID
SMIT15675
TTD Drug ID
D0Z0HH
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          TRAIL/Apo2L      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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
NCI-H322 CVCL_1556 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway.
          Imatinib      Mantle cell lymphoma     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 BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells.
          Zoledronic      Mineral excesses     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		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC3  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1B  Molecule Info 
Pathway MAP
Down-regulation Expression CLSPN  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Expression HSP20  Molecule Info 
Pathway MAP
Down-regulation Expression HSPD1  Molecule Info 
Pathway MAP
Down-regulation Expression ML-IAP  Molecule Info 
Pathway MAP
Down-regulation Expression PON2  Molecule Info 
Pathway MAP
Down-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 GP significantly enhances the anti-tumor activity of ZA in hormone- and drug-resistant prostate cancer cells by targeting many pivotal apoptosis-related proteins.
          BRD4770      Pancreatic 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		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Increase Autophagosome formation
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
HPAC CVCL_3517 Pancreatic adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of gossypol and BRD4770 increased LC3-II levels and the autophagosome number in PANC-1 cells, and the compound combination appears to act in a BNIP3-dependent manner, suggesting that these compounds act together to induce autophagy-related cell death in pancreatic cancer cells.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma 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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 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
                    Biological
                    Regulation		 Increase Cell cycle arrest in S phase
                    In-vitro Model SW982 CVCL_1734 Biphasic synovial sarcoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with L gossypol and low-concentration doxorubicin inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Gemcitabine      Solid tumour/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 [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression PMAIP1  Molecule Info 
Pathway MAP
                    In-vitro Model CNE-1 CVCL_6888 Human nasopharyngeal carcinoma Homo sapiens
CNE-2 CVCL_6889 Human nasopharyngeal carcinoma Homo sapiens
HK-1 CVCL_7047 Lung large cell carcinoma Homo sapiens
AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
SNU-1 CVCL_0099 Gastric adenocarcinoma Homo sapiens
YCC-16 CVCL_9649 Gastric adenocarcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
HONE Nasopharyngeal carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [9]
KEGG Pathway NF-kappa B signaling pathway Click to Show/Hide
2 HIF-1 signaling pathway
3 Sphingolipid signaling pathway
4 Protein processing in endoplasmic reticulum
5 PI3K-Akt signaling pathway
6 Apoptosis
7 Adrenergic signaling in cardiomyocytes
8 Focal adhesion
9 Neurotrophin signaling pathway
10 Cholinergic synapse
11 Amyotrophic lateral sclerosis (ALS)
12 Toxoplasmosis
13 Tuberculosis
14 Hepatitis B
15 Epstein-Barr virus infection
16 Pathways in cancer
17 MicroRNAs in cancer
18 Colorectal cancer
19 Prostate cancer
20 Small cell lung cancer
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 IL2 Signaling Pathway
4 IL3 Signaling Pathway
5 Leptin Signaling Pathway
6 RANKL Signaling Pathway
7 TSLP Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 Oxidative stress response
3 CCKR signaling map ST
Pathway Interaction Database Role of Calcineurin-dependent NFAT signaling in lymphocytes Click to Show/Hide
2 IL2-mediated signaling events
3 IL2 signaling events mediated by PI3K
4 Ceramide signaling pathway
5 Direct p53 effectors
6 RXR and RAR heterodimerization with other nuclear receptor
7 ATF-2 transcription factor network
8 C-MYB transcription factor network
9 HIV-1 Nef: Negative effector of Fas and TNF-alpha
10 Caspase Cascade in Apoptosis
11 Signaling events mediated by Stem cell factor receptor (c-Kit)
12 EPO signaling pathway
13 IL2 signaling events mediated by STAT5
14 Validated targets of C-MYC transcriptional repression
Reactome Activation of BAD and translocation to mitochondria Click to Show/Hide
2 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
3 The NLRP1 inflammasome
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 IL-2 Signaling Pathway
4 FAS pathway and Stress induction of HSP regulation
5 Focal Adhesion
6 Kit receptor signaling pathway
7 IL-3 Signaling Pathway
8 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
9 Apoptosis
10 Nanoparticle triggered autophagic cell death
11 Amyotrophic lateral sclerosis (ALS)
12 Integrated Pancreatic Cancer Pathway
13 Corticotropin-releasing hormone
14 Interleukin-11 Signaling Pathway
15 Prostate Cancer
16 miR-targeted genes in muscle cell - TarBase
17 miR-targeted genes in lymphocytes - TarBase
18 miR-targeted genes in leukocytes - TarBase
19 Integrated Breast Cancer Pathway
20 Integrated Cancer pathway
21 Intrinsic Pathway for Apoptosis
22 Apoptosis Modulation and Signaling
23 TP53 Network
24 Influenza A virus infection
25 IL-5 Signaling Pathway
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4204).
Reference 2 Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-62.
Reference 3 (-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007 Nov;48(11):2204-12.
Reference 4 Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination. Cell Biol Int. 2009 Nov;33(11):1165-72.
Reference 5 Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690.
Reference 6 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86.
Reference 7 Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells. Mol Med Rep. 2015 Oct;12(4):5924-32.
Reference 8 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786.
Reference 9 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
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