Natural Product: NPC225031

Natural Product IDNPC225031
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SQEKGAVAEOAXJU-TVYVFBHLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5316043
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0003480] Cinnamic acid esters

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 SQEKGAVAEOAXJU-TVYVFBHLSA-N
Standard InCHI InChI=1S/C19H18O4/c1-22-18-14-16(9-11-17(18)20)8-5-13-23-19(21)12-10-15-6-3-2-4-7-15/h2-12,14,20H,13H2,1H3/b8-5-,12-10-
SMILES COc1cc(/C=CCOC(=O)/C=Cc2ccccc2)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.12 Volume:   331.5
?
Van der Waals volume.
Dense:   0.936 LogP:   3.825
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.397
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.59
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.653 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.14 Fsp3:   0.105
MCE-18:   11.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.27
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.93
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.909 Promiscuous compounds:   0.88

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.054 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.997 Pgp-substrate:   0.0
PAMPA:   0.017
?
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):   0.012
20% Bioavailability (F20%):   0.792 30% Bioavailability (F30%):   0.856
50% Bioavailability (F50%):   0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.129 MRP1:   0.131
Plasma Protein Binding (PPB):   98.952% Volume Distribution (VD):   -0.264
Fu: 1.038%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.353
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.993
CYP2C9-inhibitor:   0.717 CYP2C9-substrate:   0.849
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.538
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.199
?
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):  10.068 Half-life (T1/2):  0.74

ADMET: Toxicity

hERG Blockers:  0.45 hERG Blockers (10um):  0.78
Human Hepatotoxicity (H-HT):  0.501 Drug-induced Liver Injury (DILI):  0.021
AMES Toxicity:  0.342 Rat Oral Acute Toxicity:  0.05
Maximum Recommended Daily Dose:  0.284 Skin Sensitization:  1.0
Carcinogencity:  0.029 Eye Corrosion:  0.353
Eye Irritation:  0.987 Respiratory Toxicity:  0.391
Drug-induced Neurotoxicity:  0.71 Ototoxicity:  0.109
Hematotoxicity:  0.005 Drug-induced Nephrotoxicity:  0.383
Genotoxicity:  0.009 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.747 Hek293 Cytotoxicity:  0.454
BCF:   1.168
?
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:   4.182
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.051
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.82
?
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
NPO11291 Styrax benzoin Species Styracaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11291 Styrax benzoin Species Styracaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11291 Styrax benzoin Species Styracaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11291 Styrax benzoin Species Styracaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11291 Styrax benzoin Species Styracaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11291 Styrax benzoin Species Styracaceae 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

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 NPC225031 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
0.8913 High Similarity NPC246704
0.7647 Intermediate Similarity NPC204466
0.7347 Intermediate Similarity NPC202474
0.7222 Intermediate Similarity NPC120225
0.7143 Intermediate Similarity NPC260952
0.7059 Intermediate Similarity NPC277460
0.6875 Remote Similarity NPC107588
0.6875 Remote Similarity NPC137537
0.6852 Remote Similarity NPC15621
0.6792 Remote Similarity NPC289459
0.6667 Remote Similarity NPC70752
0.6667 Remote Similarity NPC110313
0.661 Remote Similarity NPC482043
0.6545 Remote Similarity NPC83062
0.6522 Remote Similarity NPC208183
0.6522 Remote Similarity NPC243289
0.6316 Remote Similarity NPC213552
0.6212 Remote Similarity NPC482417
0.6207 Remote Similarity NPC60517
0.6207 Remote Similarity NPC146886
0.6207 Remote Similarity NPC135127
0.6207 Remote Similarity NPC20443
0.6102 Remote Similarity NPC110699
0.6102 Remote Similarity NPC106055
0.6 Remote Similarity NPC482462
0.5775 Remote Similarity NPC473909
0.5645 Remote Similarity NPC485282
0.5645 Remote Similarity NPC485283
0.5645 Remote Similarity NPC485281
0.5634 Remote Similarity NPC475250
0.5538 Remote Similarity NPC120852
0.5538 Remote Similarity NPC475468
0.551 Remote Similarity NPC176228
0.551 Remote Similarity NPC36108
0.551 Remote Similarity NPC233731
0.551 Remote Similarity NPC610203
0.549 Remote Similarity NPC39793
0.5472 Remote Similarity NPC109275
0.5385 Remote Similarity NPC224814
0.5283 Remote Similarity NPC160900
0.5273 Remote Similarity NPC14007
0.5192 Remote Similarity NPC78918
0.5192 Remote Similarity NPC139617
0.5179 Remote Similarity NPC48315
0.5179 Remote Similarity NPC71941
0.5102 Remote Similarity NPC167577
0.5077 Remote Similarity NPC307110
0.5077 Remote Similarity NPC157554
0.507 Remote Similarity NPC252402
0.507 Remote Similarity NPC102934

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC225031 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
0.5283 Remote Similarity NPD4379 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