Natural Product: NPC144010

Natural Product IDNPC144010
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl Tanshinonate
IUPAC Name methyl (6S)-1,6-dimethyl-10,11-dioxo-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-6-carboxylate
Synonyms Methyl Tanshinonate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2146517
PubChem CID 14610613
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 YFDKIHAZVQFLRC-FQEVSTJZSA-N
Standard InCHI InChI=1S/C20H18O5/c1-10-9-25-18-12-6-7-13-11(15(12)17(22)16(21)14(10)18)5-4-8-20(13,2)19(23)24-3/h6-7,9H,4-5,8H2,1-3H3/t20-/m0/s1
SMILES COC(=O)[C@@]1(C)CCCc2c1ccc1c2C(=O)C(=O)c2c1occ2C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   343.11
?
Van der Waals volume.
Dense:   0.985 LogP:   3.19
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.14
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.345
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   73.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.588 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.599 Fsp3:   0.35
MCE-18:   82.407
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.228 Fluc inhibitor:   0.114
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.854
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.689
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.163 Promiscuous compounds:   0.022

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.562 MDCK Permeability:   -4.512
Pgp-inhibitor:   0.989 Pgp-substrate:   0.002
PAMPA:   0.642
?
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):   0.288
20% Bioavailability (F20%):   0.031 30% Bioavailability (F30%):   0.518
50% Bioavailability (F50%):   0.537

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.956
Plasma Protein Binding (PPB):   98.676% Volume Distribution (VD):   -0.03
Fu: 1.42%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.022
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.83 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.058 CYP2C9-substrate:   0.875
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.742
CYP3A4-inhibitor:   0.674 CYP3A4-substrate:   0.877
CYP2B6-substrate:   0.014 CYP2C8-inhibitor:   1.0
HLM stability:   0.968
?
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):  4.427 Half-life (T1/2):  0.564

ADMET: Toxicity

hERG Blockers:  0.045 hERG Blockers (10um):  0.19
Human Hepatotoxicity (H-HT):  0.894 Drug-induced Liver Injury (DILI):  0.922
AMES Toxicity:  0.824 Rat Oral Acute Toxicity:  0.702
Maximum Recommended Daily Dose:  0.946 Skin Sensitization:  0.976
Carcinogencity:  0.937 Eye Corrosion:  0.0
Eye Irritation:  0.577 Respiratory Toxicity:  0.457
Drug-induced Neurotoxicity:  0.275 Ototoxicity:  0.429
Hematotoxicity:  0.832 Drug-induced Nephrotoxicity:  0.931
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.165
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.565
BCF:   1.612
?
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:   4.331
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.865
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.266
?
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]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11473439]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[12141863]
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]
NPO14979 Salvia trijuga Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20515057]
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]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14979 Salvia trijuga Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14979 Salvia trijuga Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14979 Salvia trijuga Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30139 Salvia przewalskll Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14979 Salvia trijuga 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[TCM_Taiwan]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14979 Salvia trijuga Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19451 Salvia prionitis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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 = 21100.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 9200.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus Ki = 9700.0 nM PMID[22884354]
NPT202 Individual protein Protease Human immunodeficiency virus 1 IC50 = 103500.0 nM PMID[22884354]
NPT200 Individual protein SARS coronavirus 3C-like proteinase SARS coronavirus IC50 = 10600.0 nM PMID[22884354]
NPT1123 Protein complex EZH2/SUZ12/EED complex Homo sapiens IC50 = 9600.0 nM PMID[24767850]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT196 Cell line AGS Homo sapiens IC50 > 50000.0 nM PMID[17583950]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50000.0 nM PMID[17583950]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 7480.0 nM PMID[17583950]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 7340.0 nM PMID[17583950]
NPT2 Others Unspecified n.a. IC50 = 124000.0 nM PMID[22884354]

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 NPC144010 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
0.7719 Intermediate Similarity NPC281398
0.7333 Intermediate Similarity NPC145830
0.625 Remote Similarity NPC179170
0.6154 Remote Similarity NPC221992
0.5625 Remote Similarity NPC605467
0.5538 Remote Similarity NPC117674
0.5429 Remote Similarity NPC23559
0.5303 Remote Similarity NPC307672
0.5294 Remote Similarity NPC10051
0.5294 Remote Similarity NPC299094
0.5211 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 NPC144010 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