Natural Product: NPC479645

Natural Product IDNPC479645
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GDGQOBRQTUPPDO-TVFMRDARSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 71451579
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003509] 3-prenylated chalcones

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 GDGQOBRQTUPPDO-TVFMRDARSA-N
Standard InCHI InChI=1S/C20H20O5/c1-13(12-21)2-8-16-19(24)11-9-17(20(16)25)18(23)10-5-14-3-6-15(22)7-4-14/h2-7,9-11,21-22,24-25H,8,12H2,1H3/b10-5+,13-2+
SMILES C/C(=CCc1c(ccc(C(=O)/C=C/c2ccc(cc2)O)c1O)O)/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   357.586
?
Van der Waals volume.
Dense:   0.951 LogP:   2.696
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.641
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.83
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.368 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.622 Fsp3:   0.15
MCE-18:   14.0
?
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:   0.974 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.551
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.694
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.652 Promiscuous compounds:   0.214

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.047 MDCK Permeability:   -4.811
Pgp-inhibitor:   0.943 Pgp-substrate:   0.003
PAMPA:   0.053
?
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):   0.01
20% Bioavailability (F20%):   0.817 30% Bioavailability (F30%):   0.953
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.015
Plasma Protein Binding (PPB):   95.832% Volume Distribution (VD):   -0.102
Fu: 4.404%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.512
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.607
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.693
CYP2C9-inhibitor:   0.099 CYP2C9-substrate:   0.978
CYP2D6-inhibitor:   0.615 CYP2D6-substrate:   0.406
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.126
?
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):  4.68 Half-life (T1/2):  1.227

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.471
Human Hepatotoxicity (H-HT):  0.733 Drug-induced Liver Injury (DILI):  0.485
AMES Toxicity:  0.248 Rat Oral Acute Toxicity:  0.196
Maximum Recommended Daily Dose:  0.565 Skin Sensitization:  0.976
Carcinogencity:  0.079 Eye Corrosion:  0.002
Eye Irritation:  0.978 Respiratory Toxicity:  0.93
Drug-induced Neurotoxicity:  0.523 Ototoxicity:  0.185
Hematotoxicity:  0.071 Drug-induced Nephrotoxicity:  0.344
Genotoxicity:  0.951 RPMI-8226 Immunitoxicity:  0.119
A549 Cytotoxicity:  0.26 Hek293 Cytotoxicity:  0.808
BCF:   1.301
?
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:   4.07
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.414
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.898
?
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
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. root n.a. DOI[10.1016/0031-9422(95)00135-T]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Wood n.a. n.a. PMID[23113717]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17767 Artocarpus heterophyllus Species Moraceae 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
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus FC = 1.43 n.a. PMID[30227999]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 > 100000.0 nM PMID[23113717]

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 NPC479645 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 NPC479648
0.8367 Intermediate Similarity NPC72158
0.7193 Intermediate Similarity NPC266689
0.7119 Intermediate Similarity NPC21305
0.7037 Intermediate Similarity NPC59319
0.7 Intermediate Similarity NPC475042
0.6981 Remote Similarity NPC62952
0.6909 Remote Similarity NPC213485
0.6909 Remote Similarity NPC100067
0.6727 Remote Similarity NPC162612
0.6721 Remote Similarity NPC19622
0.6721 Remote Similarity NPC112789
0.6721 Remote Similarity NPC470210
0.6508 Remote Similarity NPC484872
0.623 Remote Similarity NPC474998
0.6129 Remote Similarity NPC264112
0.6129 Remote Similarity NPC484873
0.597 Remote Similarity NPC275903
0.5965 Remote Similarity NPC98254
0.5763 Remote Similarity NPC481727
0.5763 Remote Similarity NPC481726
0.5694 Remote Similarity NPC479647
0.5694 Remote Similarity NPC479646
0.5694 Remote Similarity NPC155253
0.5686 Remote Similarity NPC19174
0.5686 Remote Similarity NPC115159
0.5593 Remote Similarity NPC169250
0.5517 Remote Similarity NPC190043
0.5517 Remote Similarity NPC30501
0.5484 Remote Similarity NPC249606
0.541 Remote Similarity NPC168105
0.5286 Remote Similarity NPC237994
0.5231 Remote Similarity NPC23126
0.5185 Remote Similarity NPC122793
0.5161 Remote Similarity NPC269694
0.5156 Remote Similarity NPC473017
0.5091 Remote Similarity NPC167205
0.5079 Remote Similarity NPC485637

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479645 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