Natural Product: NPC92740

Natural Product IDNPC92740
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YMJZBBKFFDVLLB-HXPMCKFVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101542784
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 YMJZBBKFFDVLLB-HXPMCKFVSA-N
Standard InCHI InChI=1S/C20H24O5/c1-12-15-9-13(5-4-8-21)10-18(24-3)20(15)25-19(12)14-6-7-16(22)17(11-14)23-2/h6-7,9-12,19,21-22H,4-5,8H2,1-3H3/t12-,19+/m0/s1
SMILES C[C@H]1c2cc(CCCO)cc(c2O[C@H]1c1ccc(c(c1)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
?
Van der Waals volume.
Dense:   0.964 LogP:   2.922
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.839
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.179
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.838 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.178 Fsp3:   0.4
MCE-18:   56.571
?
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:   0.204 Fluc inhibitor:   0.573
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.205
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.325
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.095 Promiscuous compounds:   0.139

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.903 MDCK Permeability:   -4.72
Pgp-inhibitor:   0.589 Pgp-substrate:   0.5
PAMPA:   0.044
?
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):   0.024
20% Bioavailability (F20%):   0.681 30% Bioavailability (F30%):   0.457
50% Bioavailability (F50%):   0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.081 MRP1:   0.925
Plasma Protein Binding (PPB):   78.499% Volume Distribution (VD):   -0.267
Fu: 21.762%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.956 BCRP inhibitor:   0.508
BSEP inhibitor:   0.957

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.144
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  7.717 Half-life (T1/2):  1.127

ADMET: Toxicity

hERG Blockers:  0.2 hERG Blockers (10um):  0.542
Human Hepatotoxicity (H-HT):  0.783 Drug-induced Liver Injury (DILI):  0.637
AMES Toxicity:  0.438 Rat Oral Acute Toxicity:  0.275
Maximum Recommended Daily Dose:  0.236 Skin Sensitization:  0.853
Carcinogencity:  0.327 Eye Corrosion:  0.098
Eye Irritation:  0.936 Respiratory Toxicity:  0.851
Drug-induced Neurotoxicity:  0.438 Ototoxicity:  0.599
Hematotoxicity:  0.54 Drug-induced Nephrotoxicity:  0.588
Genotoxicity:  0.185 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.583 Hek293 Cytotoxicity:  0.447
BCF:   0.692
?
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:   3.215
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.566
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.885
?
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
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota stem bark Kunming, Yunnan Province, China n.a. PMID[18986199]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12339 Daphne feddei Species Thymelaeaceae 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 NPC92740 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
0.8364 Intermediate Similarity NPC29799
0.8364 Intermediate Similarity NPC263367
0.8364 Intermediate Similarity NPC54743
0.6724 Remote Similarity NPC187616
0.6724 Remote Similarity NPC193026
0.6724 Remote Similarity NPC49603
0.662 Remote Similarity NPC193473
0.662 Remote Similarity NPC600128
0.6557 Remote Similarity NPC177160
0.6267 Remote Similarity NPC15956
0.6133 Remote Similarity NPC114505
0.6133 Remote Similarity NPC213074
0.6066 Remote Similarity NPC230219
0.5806 Remote Similarity NPC300757
0.5732 Remote Similarity NPC479449
0.5538 Remote Similarity NPC5851
0.5538 Remote Similarity NPC156502
0.5538 Remote Similarity NPC10737
0.5455 Remote Similarity NPC472961
0.5455 Remote Similarity NPC472962
0.5455 Remote Similarity NPC86030
0.5455 Remote Similarity NPC605857
0.5443 Remote Similarity NPC224674
0.5443 Remote Similarity NPC64475
0.5373 Remote Similarity NPC284881
0.5373 Remote Similarity NPC93433
0.5373 Remote Similarity NPC474444
0.5349 Remote Similarity NPC98624
0.5323 Remote Similarity NPC154258
0.5256 Remote Similarity NPC115203
0.5238 Remote Similarity NPC131121
0.5217 Remote Similarity NPC253878
0.5217 Remote Similarity NPC206413
0.5217 Remote Similarity NPC482649
0.5217 Remote Similarity NPC149003
0.5217 Remote Similarity NPC471414
0.5217 Remote Similarity NPC482647
0.5217 Remote Similarity NPC482648
0.5217 Remote Similarity NPC482651
0.5217 Remote Similarity NPC194244
0.5217 Remote Similarity NPC482650
0.507 Remote Similarity NPC163898
0.5063 Remote Similarity NPC472710
0.5063 Remote Similarity NPC472709
0.5056 Remote Similarity NPC316539

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC92740 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