Natural Product: NPC145830

Natural Product IDNPC145830
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tanshinone Iib
IUPAC Name 6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione
Synonyms Tanshinone IIB
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL215254
PubChem CID 318797
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0002548] Tanshinones, isotanshinones, and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey XDUXBBDRILEIEZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O4/c1-10-8-23-18-12-5-6-13-11(4-3-7-19(13,2)9-20)15(12)17(22)16(21)14(10)18/h5-6,8,20H,3-4,7,9H2,1-2H3
SMILES OCC1(C)CCCc2c1ccc1c2C(=O)C(=O)c2c1occ2C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.12 Volume:   319.66
?
Van der Waals volume.
Dense:   0.97 LogP:   2.713
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.542
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.662
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   67.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.821 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.626 Fsp3:   0.368
MCE-18:   79.385
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.11 Fluc inhibitor:   0.352
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.797
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.618
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.034 Promiscuous compounds:   0.112

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.813 MDCK Permeability:   -4.629
Pgp-inhibitor:   0.862 Pgp-substrate:   0.018
PAMPA:   0.65
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.976
20% Bioavailability (F20%):   0.136 30% Bioavailability (F30%):   0.964
50% Bioavailability (F50%):   0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.818
Plasma Protein Binding (PPB):   98.515% Volume Distribution (VD):   0.306
Fu: 1.419%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.508
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.01
BSEP inhibitor:   0.976

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.621
CYP2C19-inhibitor:   0.92 CYP2C19-substrate:   0.961
CYP2C9-inhibitor:   0.443 CYP2C9-substrate:   0.992
CYP2D6-inhibitor:   0.018 CYP2D6-substrate:   0.84
CYP3A4-inhibitor:   0.019 CYP3A4-substrate:   0.158
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.964
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.311 Half-life (T1/2):  0.604

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.327
Human Hepatotoxicity (H-HT):  0.786 Drug-induced Liver Injury (DILI):  0.893
AMES Toxicity:  0.869 Rat Oral Acute Toxicity:  0.602
Maximum Recommended Daily Dose:  0.885 Skin Sensitization:  0.911
Carcinogencity:  0.916 Eye Corrosion:  0.0
Eye Irritation:  0.616 Respiratory Toxicity:  0.56
Drug-induced Neurotoxicity:  0.515 Ototoxicity:  0.647
Hematotoxicity:  0.868 Drug-induced Nephrotoxicity:  0.656
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.27 Hek293 Cytotoxicity:  0.64
BCF:   1.69
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Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.413
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.968
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.42
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[ 17014425]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/bab.1236]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.indcrop.2010.09.006]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[11374966]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[16038550]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17583950]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[18855446]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20455578]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21775156]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23286284]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[24108414]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[27569393]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29185738]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30351923]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[3655791]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota roots n.a. n.a. PMID[9834151]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 24800.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 10700.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus Ki = 21600.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 52000.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 18000.0 nM PMID[22884354]
NPT1123 Protein complex EZH2/SUZ12/EED complex Homo sapiens IC50 = 4800.0 nM PMID[24767850]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 15550.0 nM PMID[16872829]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 20000.0 nM PMID[16872829]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC145830 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8 Intermediate Similarity NPC281398
0.7333 Intermediate Similarity NPC144010
0.7 Intermediate Similarity NPC179170
0.6885 Remote Similarity NPC221992
0.5938 Remote Similarity NPC10051
0.5938 Remote Similarity NPC299094
0.5806 Remote Similarity NPC605467
0.5714 Remote Similarity NPC117674
0.5588 Remote Similarity NPC23559
0.5469 Remote Similarity NPC307672
0.5362 Remote Similarity NPC608807

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC145830 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data