Natural Product: NPC481090

Natural Product IDNPC481090
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DFLXMFQVYNRTNJ-XIKOKIGWSA-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: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 DFLXMFQVYNRTNJ-XIKOKIGWSA-N
Standard InCHI InChI=1S/C18H20O6/c1-21-15-6-10(4-5-13(15)20)18-12(9-19)11-7-16(22-2)17(23-3)8-14(11)24-18/h4-8,12,18-20H,9H2,1-3H3/t12-,18+/m1/s1
SMILES COc1cc(ccc1O)[C@H]1[C@H](CO)c2cc(c(cc2O1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.13 Volume:   331.137
?
Van der Waals volume.
Dense:   1.003 LogP:   2.137
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.492
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.836
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   16.0
TPSA:   77.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.876 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.078 Fsp3:   0.333
MCE-18:   57.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.301 Fluc inhibitor:   0.635
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.294
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.144
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.281 Promiscuous compounds:   0.673

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.258 MDCK Permeability:   -4.959
Pgp-inhibitor:   0.934 Pgp-substrate:   0.246
PAMPA:   0.009
?
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):   0.08
20% Bioavailability (F20%):   0.145 30% Bioavailability (F30%):   0.26
50% Bioavailability (F50%):   0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.726
Plasma Protein Binding (PPB):   77.349% Volume Distribution (VD):   0.078
Fu: 25.715%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.98
BSEP inhibitor:   0.897

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.976 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.438 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.964 CYP2D6-substrate:   0.697
CYP3A4-inhibitor:   0.989 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.004
?
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):  8.979 Half-life (T1/2):  1.945

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.432
Human Hepatotoxicity (H-HT):  0.781 Drug-induced Liver Injury (DILI):  0.545
AMES Toxicity:  0.547 Rat Oral Acute Toxicity:  0.36
Maximum Recommended Daily Dose:  0.287 Skin Sensitization:  0.8
Carcinogencity:  0.522 Eye Corrosion:  0.102
Eye Irritation:  0.943 Respiratory Toxicity:  0.68
Drug-induced Neurotoxicity:  0.592 Ototoxicity:  0.463
Hematotoxicity:  0.449 Drug-induced Nephrotoxicity:  0.386
Genotoxicity:  0.475 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.268 Hek293 Cytotoxicity:  0.356
BCF:   0.806
?
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:   3.225
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.381
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.689
?
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
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[12542368]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[28139925]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[31184894]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18950 Cephalotaxus fortunei Species Taxaceae 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
NPT116 Cell line HL-60 Homo sapiens GI < 50.0 % PMID[28139925]
NPT81 Cell line A549 Homo sapiens GI < 50.0 % PMID[28139925]

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 NPC481090 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
0.614 Remote Similarity NPC300757
0.5862 Remote Similarity NPC180901
0.5833 Remote Similarity NPC29799
0.5833 Remote Similarity NPC156502
0.5833 Remote Similarity NPC263367
0.5833 Remote Similarity NPC10737
0.5833 Remote Similarity NPC177160
0.5833 Remote Similarity NPC54743
0.5738 Remote Similarity NPC472961
0.5738 Remote Similarity NPC472962
0.5645 Remote Similarity NPC284881
0.5645 Remote Similarity NPC93433
0.5645 Remote Similarity NPC474444
0.5536 Remote Similarity NPC160283
0.5469 Remote Similarity NPC253878
0.5469 Remote Similarity NPC206413
0.5469 Remote Similarity NPC482649
0.5469 Remote Similarity NPC149003
0.5469 Remote Similarity NPC471414
0.5469 Remote Similarity NPC482647
0.5469 Remote Similarity NPC482648
0.5469 Remote Similarity NPC482651
0.5469 Remote Similarity NPC194244
0.5469 Remote Similarity NPC482650
0.5439 Remote Similarity NPC103976
0.5312 Remote Similarity NPC209985
0.5303 Remote Similarity NPC163898

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481090 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