Natural Product: NPC51032

Natural Product IDNPC51032
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OAUREGNZECGNQS-LJQANCHMSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 26436537
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 OAUREGNZECGNQS-LJQANCHMSA-N
Standard InCHI InChI=1S/C20H20O4/c1-12(2)3-4-14-9-16-18(23)11-19(24-20(16)10-17(14)22)13-5-7-15(21)8-6-13/h3,5-10,19,21-22H,4,11H2,1-2H3/t19-/m1/s1
SMILES CC(=CCc1cc2C(=O)C[C@H](c3ccc(cc3)O)Oc2cc1O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   324.14 Volume:   342.876
?
Van der Waals volume.
Dense:   0.945 LogP:   4.077
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.45
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.714
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.826 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.073 Fsp3:   0.25
MCE-18:   56.88
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.846 Fluc inhibitor:   0.92
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.803
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.258
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.414 Promiscuous compounds:   0.096

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.832 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.961 Pgp-substrate:   0.118
PAMPA:   0.613
?
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):   0.001
20% Bioavailability (F20%):   0.086 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.895
Plasma Protein Binding (PPB):   94.278% Volume Distribution (VD):   0.21
Fu: 5.525%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.557
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   1.0
BSEP inhibitor:   0.962

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.834 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.021 CYP2C9-substrate:   0.063
CYP2D6-inhibitor:   0.829 CYP2D6-substrate:   0.921
CYP3A4-inhibitor:   0.004 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):  5.512 Half-life (T1/2):  1.637

ADMET: Toxicity

hERG Blockers:  0.134 hERG Blockers (10um):  0.542
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.351
AMES Toxicity:  0.736 Rat Oral Acute Toxicity:  0.682
Maximum Recommended Daily Dose:  0.669 Skin Sensitization:  0.843
Carcinogencity:  0.604 Eye Corrosion:  0.001
Eye Irritation:  0.948 Respiratory Toxicity:  0.289
Drug-induced Neurotoxicity:  0.921 Ototoxicity:  0.516
Hematotoxicity:  0.164 Drug-induced Nephrotoxicity:  0.813
Genotoxicity:  0.979 RPMI-8226 Immunitoxicity:  0.097
A549 Cytotoxicity:  0.447 Hek293 Cytotoxicity:  0.711
BCF:   1.645
?
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:   4.698
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.775
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.351
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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
NPO10080 Teucrium betonicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10080 Teucrium betonicum 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens Inhibition = 34.0 % PMID[29763806]
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 17.0 % PMID[29763806]
NPT30107 Single protein Amyloid-beta A4 protein Homo sapiens Inhibition = 19.0 % PMID[29763806]

In vitro activity

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

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 NPC51032 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
1.0 High Similarity NPC39329
0.7719 Intermediate Similarity NPC221432
0.7719 Intermediate Similarity NPC257097
0.7368 Intermediate Similarity NPC169591
0.7368 Intermediate Similarity NPC298223
0.7368 Intermediate Similarity NPC604412
0.7069 Intermediate Similarity NPC143896
0.6833 Remote Similarity NPC75049
0.65 Remote Similarity NPC164980
0.6452 Remote Similarity NPC109223
0.6452 Remote Similarity NPC68104
0.6452 Remote Similarity NPC220998
0.6452 Remote Similarity NPC10937
0.6349 Remote Similarity NPC125855
0.6349 Remote Similarity NPC76338
0.6349 Remote Similarity NPC250242
0.6308 Remote Similarity NPC291508
0.6296 Remote Similarity NPC329225
0.6296 Remote Similarity NPC147686
0.619 Remote Similarity NPC197252
0.6129 Remote Similarity NPC150408
0.6032 Remote Similarity NPC69674
0.6032 Remote Similarity NPC171651
0.5873 Remote Similarity NPC107572
0.5873 Remote Similarity NPC32739
0.5797 Remote Similarity NPC228504
0.5714 Remote Similarity NPC258630
0.5694 Remote Similarity NPC209040
0.5694 Remote Similarity NPC110303
0.5694 Remote Similarity NPC601247
0.5652 Remote Similarity NPC39752
0.5625 Remote Similarity NPC1089
0.5625 Remote Similarity NPC236766
0.5625 Remote Similarity NPC472580
0.5593 Remote Similarity NPC1612
0.5593 Remote Similarity NPC183959
0.5556 Remote Similarity NPC197351
0.5556 Remote Similarity NPC185276
0.5538 Remote Similarity NPC265040
0.5517 Remote Similarity NPC476480
0.5517 Remote Similarity NPC84585
0.5507 Remote Similarity NPC36275
0.55 Remote Similarity NPC324386
0.5455 Remote Similarity NPC66515
0.5455 Remote Similarity NPC310130
0.5424 Remote Similarity NPC32441
0.5424 Remote Similarity NPC79943
0.5417 Remote Similarity NPC488556
0.541 Remote Similarity NPC469764
0.5385 Remote Similarity NPC245482
0.5373 Remote Similarity NPC223500
0.5373 Remote Similarity NPC106976
0.5342 Remote Similarity NPC472627
0.5303 Remote Similarity NPC149026
0.5294 Remote Similarity NPC608140
0.5286 Remote Similarity NPC35038
0.5278 Remote Similarity NPC472629
0.5254 Remote Similarity NPC225153
0.5254 Remote Similarity NPC479876
0.5246 Remote Similarity NPC300668
0.5246 Remote Similarity NPC329203
0.5246 Remote Similarity NPC222342
0.5231 Remote Similarity NPC482704
0.5224 Remote Similarity NPC17170
0.5205 Remote Similarity NPC479215
0.52 Remote Similarity NPC472628
0.5167 Remote Similarity NPC264083
0.5161 Remote Similarity NPC210084
0.5152 Remote Similarity NPC91560
0.5147 Remote Similarity NPC166689
0.5143 Remote Similarity NPC470890
0.5143 Remote Similarity NPC200761
0.5143 Remote Similarity NPC473078
0.5139 Remote Similarity NPC479211
0.5068 Remote Similarity NPC485619
0.5068 Remote Similarity NPC479213

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC51032 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
0.6296 Remote Similarity NPD1549 Phase 2
0.5424 Remote Similarity NPD1552 Clinical (unspecified phase)

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