Natural Product (NP) Details

General Information of the NP (ID: NP1965)
Name
Tanshinone IIA
Synonyms
Tanshinone IIA; 568-72-9; Tanshinone II; Dan Shen Ketone; Tanshinone B; Tanshinon II; 1,6,6-Trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione; UNII-4GPC9FQG6L; 1,6,6-trimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione; Phenanthro[1,2-b]furan-10,11-dione, 6,7,8,9-tetrahydro-1,6,6-trimethyl-; C19H18O3; 4GPC9FQG6L; MLS001048863; MFCD00238692; NSC686519; SMR000387068; 1,6,6-trimethyl-8,9-dihydro-7H-naphtho[1,2-g]benzofuran-10,11-dione; Phenanthro(1,2-b)furan-10,11-dione, 6,7,8,9-tetrahydro-1,6,6-trimethyl-; tanshinone II A; SR-01000758926; NSC 686518; tanshinone-IIA; HSDB 8104; Tanshinone centoA; Tanshinone 2-A; Tanshinone Iia ,(S); BSPBio_001597; BSPBio_002426; KBioGR_000317; KBioSS_000317; MLS006011834; SPECTRUM1505824; CHEMBL187266; cid_164676; SCHEMBL2026738; Tanshinone IIA (Tanshinone B); BDBM83922; KBio2_000317; KBio2_002885; KBio2_005453; KBio3_000633; KBio3_000634; DTXSID60205352; CHEBI:108595; Bio2_000317; Bio2_000797; HMS1361P19; HMS1791P19; HMS1989P19; HMS2089H08; HMS2270D15; HMS3402P19; HMS3656C11; NP474; BCP28199; HY-N0135; Tanshinone IIA, analytical standard; ZINC1650576; BBL028449; CT0134; s2365; STK801917; Tanshinone IIA, >=97% (HPLC); AKOS004120032; AC-1440; ACN-035345; CCG-207955; CCG-208275; NSC-686519; IDI1_034067; NCGC00095709-01; NCGC00095709-02; NCGC00095709-03; NCGC00095709-04; NCGC00095709-05; NCGC00095709-06; NCGC00095709-08; AK168188; AS-16136; NCI60_031209; S594; AB0018692; NCGC00095709-02!TANSHINONE IIA; FT-0652880; N1846; SW220025-1; W-2832; 568T729; Q-100654; SR-01000758926-2; SR-01000758926-4; SR-01000758926-5; BRD-K00141480-001-03-0; Q27187517; Phenanthro[1,11-dione, 6,7,8,9-tetrahydro-1,6,6-trimethyl-; Tanshinone IIA, European Pharmacopoeia (EP) Reference Standard; Tanshinone IIA, United States Pharmacopeia (USP) Reference Standard; 1,6,6-Trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione #; 1,6,6-trimethyl-8,9-dihydro-7H-naphtho[1,2-g]benzofuran-10,11-quinone; 1,6,6-trimethyl-8,9-dihydro-7H-naphtho[8,7-g]benzofuran-10,11-dione; 6,7,8,9-Tetrahydro-1,6,6-trimethylphenanthro[1,2-b]furan-10,11-dione
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Species Origin Salvia miltiorrhiza ...     Click to Show/Hide
Salvia miltiorrhiza
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Lamiales
Family: Lamiaceae
Genus: Salvia
Species: Salvia miltiorrhiza
Disease Myocardial infarction [ICD-11: BA41] Phase 4 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.612
 
MDCK Permeability
 -4.662
 
PAMPA
 - - -
 
HIA
 ++
 
Distribution
VDss
 0.451
 
PPB
 99.3%
 
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
 4.88
 
T1/2
 0.499
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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Formula
C19H18O3
PubChem CID
164676
Canonical SMILES
CC1=COC2=C1C(=O)C(=O)C3=C2C=CC4=C3CCCC4(C)C
InChI
1S/C19H18O3/c1-10-9-22-18-12-6-7-13-11(5-4-8-19(13,2)3)15(12)17(21)16(20)14(10)18/h6-7,9H,4-5,8H2,1-3H3
InChIKey
HYXITZLLTYIPOF-UHFFFAOYSA-N
CAS Number
CAS 568-72-9
ChEBI ID
CHEBI:108595
Herb ID
HBIN045506
SymMap ID
SMIT00353
TCMSP ID
MOL007154
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Nutlin-3      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		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
NALM-6 CVCL_0092 Adult B acute lymphoblastic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 The combination of Nutlin-3 and Tanshinone IIA exerts synergistic anti-leukemia effects by regulating the p53 and AKT/mTOR pathways.
          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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Tan-IIA combined with sorafenib or SC-1 exerted synergistic cytotoxicity in HCC 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 [4]
                    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 MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Tan IIA enhanced the chemotherapeutic effect of Dox against breast cancer while reducing its toxic side effects including weight loss, myelosuppression, cardiotoxicity, and nephrotoxicity.
          Atorvastatin      Cardiovascular disease     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
                    In-vivo Model Six-week old male ApoE KO mice were used in this study.
                    Experimental
                    Result(s)		 Tan in conjunction with Ato represents an effective combination therapy to comprehensively combat atherogenesis in ApoE / mice by reducing plaque size and stabilizing vulnerable atheromatous plaques.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [7]
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 ClinicalTrials.gov (NCT02524964) Sodium Tanshinone IIA Sulfonate in Left Ventricular Remodeling Secondary to Acute Myocardial Infarction
Reference 2 The combination of Nutlin-3 and Tanshinone IIA promotes synergistic cytotoxicity in acute leukemic cells expressing wild-type p53 by co-regulating MDM2-P53 and the AKT/mTOR pathway. Int J Biochem Cell Biol. 2019 Jan;106:8-20.
Reference 3 Synergistic antitumor effects of tanshinone IIA and sorafenib or its derivative SC-1 in hepatocellular carcinoma cells. Onco Targets Ther. 2018 Mar 29;11:1777-1785.
Reference 4 Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer. Phytother Res. 2019 Jun;33(6):1658-1669.
Reference 5 Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way. BMC Cancer. 2016 Nov 18;16(1):899.
Reference 6 Effectiveness of combination therapy of atorvastatin and non lipid-modifying tanshinone IIA from Danshen in a mouse model of atherosclerosis. Int J Cardiol. 2014 Jul 1;174(3):878-80.
Reference 7 Tanshinone IIA induced cell death via miR30b-p53-PTPN11/SHP2 signaling pathway in human hepatocellular carcinoma cells. Eur J Pharmacol. 2017 Feb 5;796:233-241.
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