Natural Product: NPC40868

Natural Product IDNPC40868
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RWDSADRZXTYPMY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5746354
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 RWDSADRZXTYPMY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O6/c1-10(2)3-5-13-16(23)8-17(24)18-19(25)14(9-26-20(13)18)12-6-4-11(21)7-15(12)22/h3-4,6-9,21-24H,5H2,1-2H3
SMILES CC(=CCc1c(cc(c2c(=O)c(coc12)c1ccc(cc1O)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   357.82
?
Van der Waals volume.
Dense:   0.99 LogP:   2.937
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.804
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.915
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.533 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.909 Fsp3:   0.15
MCE-18:   20.0
?
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:   0
Colloidal aggregators:   0.865 Fluc inhibitor:   0.424
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.516
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.385 Promiscuous compounds:   0.103

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.18 MDCK Permeability:   -4.833
Pgp-inhibitor:   0.036 Pgp-substrate:   0.099
PAMPA:   0.573
?
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):   0.009
20% Bioavailability (F20%):   0.77 30% Bioavailability (F30%):   0.977
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.893
Plasma Protein Binding (PPB):   92.332% Volume Distribution (VD):   0.371
Fu: 8.068%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.953
BSEP inhibitor:   0.235

ADMET: Metabolism

CYP1A2-inhibitor:   0.024 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.892 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   0.925
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.111
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  1.44 Half-life (T1/2):  1.979

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.525
Human Hepatotoxicity (H-HT):  0.493 Drug-induced Liver Injury (DILI):  0.701
AMES Toxicity:  0.636 Rat Oral Acute Toxicity:  0.772
Maximum Recommended Daily Dose:  0.804 Skin Sensitization:  0.858
Carcinogencity:  0.439 Eye Corrosion:  0.0
Eye Irritation:  0.939 Respiratory Toxicity:  0.968
Drug-induced Neurotoxicity:  0.116 Ototoxicity:  0.231
Hematotoxicity:  0.06 Drug-induced Nephrotoxicity:  0.211
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.54 Hek293 Cytotoxicity:  0.818
BCF:   1.575
?
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:   4.674
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.643
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.25
?
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
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 34.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.78 n.a. PMID[28835349]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 18.2 % PMID[28140583]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 2.1 n.a. PMID[28140583]
NPT741 Individual protein Tyrosinase Homo sapiens Inhibition = 49.6 % PMID[28140583]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens GI = 31.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 13.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 5.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 9.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 10.3 % PMID[28140583]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 0.0 % PMID[28140583]
NPT81 Cell line A549 Homo sapiens Inhibition = 4.2 % PMID[28140583]
NPT83 Cell line MCF7 Homo sapiens Inhibition = 7.4 % PMID[28140583]
NPT660 Cell line SW480 Homo sapiens Inhibition = 4.2 % PMID[28140583]
NPT2 Others Unspecified n.a. Inhibition = 8.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 17.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 0.0 % PMID[28140583]

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
- Mus musculus LD50 = 5.044292264 mg/kg TOXRIC

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 NPC40868 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
0.7966 Intermediate Similarity NPC144118
0.7869 Intermediate Similarity NPC92075
0.7258 Intermediate Similarity NPC38545
0.6923 Remote Similarity NPC80962
0.6667 Remote Similarity NPC52789
0.6567 Remote Similarity NPC130589
0.6522 Remote Similarity NPC610891
0.6515 Remote Similarity NPC268204
0.6418 Remote Similarity NPC169162
0.6377 Remote Similarity NPC604255
0.6119 Remote Similarity NPC604003
0.5915 Remote Similarity NPC26051
0.5882 Remote Similarity NPC222298
0.5882 Remote Similarity NPC96565
0.5867 Remote Similarity NPC200625
0.5797 Remote Similarity NPC232947
0.5753 Remote Similarity NPC78103
0.5735 Remote Similarity NPC204985
0.5714 Remote Similarity NPC91701
0.5645 Remote Similarity NPC87545
0.5571 Remote Similarity NPC606794
0.5522 Remote Similarity NPC9117
0.5522 Remote Similarity NPC220062
0.5443 Remote Similarity NPC349624
0.5405 Remote Similarity NPC117836
0.5405 Remote Similarity NPC15435
0.5217 Remote Similarity NPC227122
0.5211 Remote Similarity NPC171916
0.5139 Remote Similarity NPC213659
0.5139 Remote Similarity NPC85131
0.5139 Remote Similarity NPC326109
0.5128 Remote Similarity NPC77856
0.5072 Remote Similarity NPC63187
0.5072 Remote Similarity NPC90665
0.507 Remote Similarity NPC55832
0.5065 Remote Similarity NPC604254

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC40868 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