Natural Product: NPC479206

Natural Product IDNPC479206
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 POQWEOONKMUETI-LFQPHHBNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 POQWEOONKMUETI-LFQPHHBNSA-N
Standard InCHI InChI=1S/C25H28O4/c1-16(2)5-4-13-25(3)14-12-20-22(29-25)11-10-19-21(27)15-23(28-24(19)20)17-6-8-18(26)9-7-17/h5-11,23,26H,4,12-15H2,1-3H3/t23-,25?/m0/s1
SMILES CC(=CCCC1(C)CCc2c(ccc3C(=O)C[C@@H](c4ccc(cc4)O)Oc23)O1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.2 Volume:   420.799
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Van der Waals volume.
Dense:   0.932 LogP:   5.626
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.291
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.547
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   55.76
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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:   0.655 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.654 Fsp3:   0.4
MCE-18:   78.857
?
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:   0.969 Fluc inhibitor:   0.841
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.421
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.639
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.22 Promiscuous compounds:   0.059

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.762 MDCK Permeability:   -4.655
Pgp-inhibitor:   0.995 Pgp-substrate:   0.035
PAMPA:   0.008
?
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):   0.0
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.025
50% Bioavailability (F50%):   0.865

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.983
Plasma Protein Binding (PPB):   96.882% Volume Distribution (VD):   0.393
Fu: 3.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.594
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.984
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.203 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.119 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.248 CYP2D6-substrate:   0.067
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.962
?
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):  7.674 Half-life (T1/2):  0.893

ADMET: Toxicity

hERG Blockers:  0.487 hERG Blockers (10um):  0.664
Human Hepatotoxicity (H-HT):  0.85 Drug-induced Liver Injury (DILI):  0.31
AMES Toxicity:  0.5 Rat Oral Acute Toxicity:  0.689
Maximum Recommended Daily Dose:  0.691 Skin Sensitization:  0.926
Carcinogencity:  0.386 Eye Corrosion:  0.002
Eye Irritation:  0.852 Respiratory Toxicity:  0.865
Drug-induced Neurotoxicity:  0.897 Ototoxicity:  0.604
Hematotoxicity:  0.193 Drug-induced Nephrotoxicity:  0.597
Genotoxicity:  0.692 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.491 Hek293 Cytotoxicity:  0.525
BCF:   2.096
?
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:   5.18
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.821
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.402
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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
NPO40094 Dalbergia velutina Species Fabaceae Eukaryota Stems n.a. n.a. PMID[30719909]

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
NPT91 Cell line KB Homo sapiens IC50 = 9900.0 nM PMID[30719909]
NPT83 Cell line MCF7 Homo sapiens IC50 = 9900.0 nM PMID[30719909]
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[30719909]
NPT139 Cell line HT-29 Homo sapiens IC50 > 10000.0 nM PMID[30719909]
NPT20987 Cell line HeLa S3 Homo sapiens IC50 = 8100.0 nM PMID[30719909]

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 NPC479206 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
0.7794 Intermediate Similarity NPC479210
0.7681 Intermediate Similarity NPC479219
0.7647 Intermediate Similarity NPC479209
0.7536 Intermediate Similarity NPC479220
0.7536 Intermediate Similarity NPC479221
0.7286 Intermediate Similarity NPC479207
0.7183 Intermediate Similarity NPC479218
0.7083 Intermediate Similarity NPC479208
0.6053 Remote Similarity NPC479216
0.5584 Remote Similarity NPC475052
0.5513 Remote Similarity NPC488428
0.5513 Remote Similarity NPC488427
0.5455 Remote Similarity NPC479214
0.5395 Remote Similarity NPC36275
0.5352 Remote Similarity NPC164980
0.519 Remote Similarity NPC488553
0.5119 Remote Similarity NPC488431
0.5119 Remote Similarity NPC488432

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479206 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