Natural Product: NPC604372

Natural Product IDNPC604372
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BVNKWNRETUIZFZ-XCLFUZPHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL4472700
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 BVNKWNRETUIZFZ-XCLFUZPHSA-N
Standard InCHI InChI=1S/C22H26O6/c1-7-8-14-9-16(23-3)22-19(10-14)28-20(13(2)27-22)15-11-17(24-4)21(26-6)18(12-15)25-5/h7,9-13,20H,1,8H2,2-6H3/t13-,20+/m1/s1
SMILES C=CCc1cc(OC)c2c(c1)O[C@H](c1cc(OC)c(OC)c(OC)c1)[C@@H](C)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.17 Volume:   397.685
?
Van der Waals volume.
Dense:   0.971 LogP:   3.317
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.335
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.798
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.66 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.368 Fsp3:   0.364
MCE-18:   59.533
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.392 Fluc inhibitor:   0.392
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.208
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.364 Promiscuous compounds:   0.053

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.695 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.996 Pgp-substrate:   0.0
PAMPA:   0.0
?
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%):   0.046 30% Bioavailability (F30%):   0.06
50% Bioavailability (F50%):   0.176

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.987 MRP1:   0.994
Plasma Protein Binding (PPB):   93.488% Volume Distribution (VD):   0.266
Fu: 7.201%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.597
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.809 CYP1A2-substrate:   0.778
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.025
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.023
?
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):  8.302 Half-life (T1/2):  1.581

ADMET: Toxicity

hERG Blockers:  0.196 hERG Blockers (10um):  0.641
Human Hepatotoxicity (H-HT):  0.574 Drug-induced Liver Injury (DILI):  0.764
AMES Toxicity:  0.274 Rat Oral Acute Toxicity:  0.493
Maximum Recommended Daily Dose:  0.377 Skin Sensitization:  0.817
Carcinogencity:  0.521 Eye Corrosion:  0.466
Eye Irritation:  0.927 Respiratory Toxicity:  0.9
Drug-induced Neurotoxicity:  0.784 Ototoxicity:  0.332
Hematotoxicity:  0.379 Drug-induced Nephrotoxicity:  0.268
Genotoxicity:  0.126 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.262 Hek293 Cytotoxicity:  0.382
BCF:   2.273
?
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:   3.936
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.842
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.784
?
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
NPO33533 Aniba sp. Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[22901310]
NPO33533 Aniba sp. Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19194 Licaria rigida Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54146 Licaria sp. Genus Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19194 Licaria rigida Species Lauraceae 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
NPT28438 Unchecked Unchecked n.a. Ratio CC50/IC50 = 1.21 n.a. PMID[30485098]
NPT30103 Organism Hepatitis C virus Hepacivirus hominis IC50 = 30000.0 nM PMID[30485098]
NPT27323 Cell line Huh7.5.1 Homo sapiens CC50 = 36200.0 nM PMID[30485098]

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 NPC604372 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
0.7255 Intermediate Similarity NPC609679
0.6667 Remote Similarity NPC307042
0.6 Remote Similarity NPC261661
0.6 Remote Similarity NPC601166
0.5897 Remote Similarity NPC204120
0.5849 Remote Similarity NPC210674
0.5849 Remote Similarity NPC104934
0.5636 Remote Similarity NPC485477
0.551 Remote Similarity NPC28326
0.54 Remote Similarity NPC202582
0.54 Remote Similarity NPC243749

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604372 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