Natural Product: NPC473136

Natural Product IDNPC473136
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XLFPSTUJYBEZIQ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3617765
PubChem CID 86295273
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002652] Cyclic diarylheptanoids
          • [CHEMONTID:0003524] Meta,meta-bridged biphenyls

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 XLFPSTUJYBEZIQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O5/c20-15-5-1-11-3-7-17(22)19(24)18(23)8-4-12-2-6-16(21)14(10-12)13(15)9-11/h1-2,5-6,9-10,19-21,24H,3-4,7-8H2
SMILES C1CC(=O)C(C(=O)CCC2=CC(=C(C=C2)O)C3=C(C=CC1=C3)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.12 Volume:   334.37
?
Van der Waals volume.
Dense:   0.975 LogP:   0.993
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.239
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.801
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   23.0
TPSA:   94.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.645 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.423 Fsp3:   0.263
MCE-18:   43.5
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.24 Fluc inhibitor:   0.101
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.772
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.243
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.372 Promiscuous compounds:   0.16

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.709 MDCK Permeability:   -4.721
Pgp-inhibitor:   0.121 Pgp-substrate:   0.035
PAMPA:   0.809
?
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):   0.157
20% Bioavailability (F20%):   0.078 30% Bioavailability (F30%):   0.554
50% Bioavailability (F50%):   0.93

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.748
Plasma Protein Binding (PPB):   91.014% Volume Distribution (VD):   -0.168
Fu: 6.736%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.572
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.041
BSEP inhibitor:   0.975

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.02 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.212
HLM stability:   0.888
?
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):  8.892 Half-life (T1/2):  1.654

ADMET: Toxicity

hERG Blockers:  0.039 hERG Blockers (10um):  0.393
Human Hepatotoxicity (H-HT):  0.587 Drug-induced Liver Injury (DILI):  0.244
AMES Toxicity:  0.586 Rat Oral Acute Toxicity:  0.51
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.323
Carcinogencity:  0.481 Eye Corrosion:  0.0
Eye Irritation:  0.637 Respiratory Toxicity:  0.74
Drug-induced Neurotoxicity:  0.568 Ototoxicity:  0.624
Hematotoxicity:  0.274 Drug-induced Nephrotoxicity:  0.438
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.444 Hek293 Cytotoxicity:  0.499
BCF:   0.775
?
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:   3.301
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.422
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.85
?
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
NPO15361 Alnus japonica Species Betulaceae Eukaryota bark n.a. n.a. PMID[20045319]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[26341132]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15361 Alnus japonica Species Betulaceae 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
NPT2 Others Unspecified n.a. Activity = 11.6 % PMID[17067147]

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 NPC473136 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
0.7209 Intermediate Similarity NPC488675
0.7045 Intermediate Similarity NPC488578
0.7045 Intermediate Similarity NPC231767
0.7045 Intermediate Similarity NPC608772
0.6818 Remote Similarity NPC182240
0.6667 Remote Similarity NPC608771
0.6512 Remote Similarity NPC602856
0.6364 Remote Similarity NPC286222
0.6216 Remote Similarity NPC138942
0.5957 Remote Similarity NPC601260
0.5652 Remote Similarity NPC31936
0.5652 Remote Similarity NPC488677
0.5532 Remote Similarity NPC127975
0.5435 Remote Similarity NPC262365
0.5349 Remote Similarity NPC473137
0.5273 Remote Similarity NPC152209
0.5238 Remote Similarity NPC488678
0.5227 Remote Similarity NPC308689
0.5208 Remote Similarity NPC488580
0.5208 Remote Similarity NPC611070
0.5128 Remote Similarity NPC288411
0.5082 Remote Similarity NPC488676
0.5082 Remote Similarity NPC606722

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473136 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