Natural Product: NPC20631

Natural Product IDNPC20631
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Conferol
IUPAC Name 7-[[(1R,4aS,6S,8aR)-6-hydroxy-2,5,5,8a-tetramethyl-1,4,4a,6,7,8-hexahydronaphthalen-1-yl]methoxy]chromen-2-one
Synonyms Conferol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1078139
PubChem CID 11892267
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 MCTDXPDDZLFJHR-HWXYTADMSA-N
Standard InCHI InChI=1S/C24H30O4/c1-15-5-9-20-23(2,3)21(25)11-12-24(20,4)18(15)14-27-17-8-6-16-7-10-22(26)28-19(16)13-17/h5-8,10,13,18,20-21,25H,9,11-12,14H2,1-4H3/t18-,20-,21+,24+/m1/s1
SMILES CC1=CC[C@H]2[C@@]([C@@H]1COc1ccc3c(c1)oc(=O)cc3)(C)CC[C@@H](C2(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.21 Volume:   408.776
?
Van der Waals volume.
Dense:   0.935 LogP:   4.446
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.821
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.961
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.603 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.879 Fsp3:   0.542
MCE-18:   89.243
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.826 Fluc inhibitor:   0.76
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.897
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.121
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.043 Promiscuous compounds:   0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.01 MDCK Permeability:   -4.652
Pgp-inhibitor:   0.122 Pgp-substrate:   0.002
PAMPA:   0.507
?
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%):   0.814 30% Bioavailability (F30%):   0.571
50% Bioavailability (F50%):   0.239

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   1.0
Plasma Protein Binding (PPB):   93.768% Volume Distribution (VD):   -0.208
Fu: 4.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.403 CYP1A2-substrate:   0.107
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.062
CYP2C9-inhibitor:   0.985 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.385
CYP3A4-inhibitor:   0.936 CYP3A4-substrate:   0.849
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   0.904
HLM stability:   0.661
?
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):  10.548 Half-life (T1/2):  0.854

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.192
Human Hepatotoxicity (H-HT):  0.394 Drug-induced Liver Injury (DILI):  0.798
AMES Toxicity:  0.448 Rat Oral Acute Toxicity:  0.269
Maximum Recommended Daily Dose:  0.573 Skin Sensitization:  0.125
Carcinogencity:  0.838 Eye Corrosion:  0.015
Eye Irritation:  0.89 Respiratory Toxicity:  0.652
Drug-induced Neurotoxicity:  0.051 Ototoxicity:  0.4
Hematotoxicity:  0.281 Drug-induced Nephrotoxicity:  0.242
Genotoxicity:  0.614 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.312 Hek293 Cytotoxicity:  0.457
BCF:   1.198
?
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:   3.968
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.237
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.843
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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
NPO10996 Ferula assa-foetida Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[19691312]
NPO10996 Ferula assa-foetida Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[31707845]
NPO10996 Ferula assa-foetida Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[385653815]
NPO10996 Ferula assa-foetida Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10996 Ferula assa-foetida Species Apiaceae 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
NPT65 Cell line HepG2 Homo sapiens IC50 = 0.51 ug.mL-1 PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 20.0 ug.mL-1 PMID[21077124]
NPT83 Cell line MCF7 Homo sapiens IC50 = 3.38 ug.mL-1 PMID[10425119]
NPT1031 Cell line Ca9-22 Homo sapiens IC50 = 6.83 ug.mL-1 DrugMatrix in vivo data: Pathology
NPT81 Cell line A549 Homo sapiens IC50 = 9.08 ug.mL-1 PubChem BioAssay data set
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2.63 ug.mL-1 PMID[19691312]
NPT742 Organism Influenza A virus Influenza A virus IC50 = 0.47 ug.mL-1 PMID[26081761]
NPT742 Organism Influenza A virus Influenza A virus IC90 = 0.83 ug.mL-1 PMID[18440233]

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 NPC20631 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 NPC93640
0.7534 Intermediate Similarity NPC138149
0.7534 Intermediate Similarity NPC603929
0.7432 Intermediate Similarity NPC318867
0.7432 Intermediate Similarity NPC146014
0.6711 Remote Similarity NPC609195
0.6154 Remote Similarity NPC251372
0.5679 Remote Similarity NPC131198
0.5467 Remote Similarity NPC479427
0.5385 Remote Similarity NPC29734
0.5362 Remote Similarity NPC281356
0.5349 Remote Similarity NPC601811
0.5325 Remote Similarity NPC479428
0.5325 Remote Similarity NPC121740
0.5325 Remote Similarity NPC224774
0.5325 Remote Similarity NPC113098
0.5325 Remote Similarity NPC33279
0.5294 Remote Similarity NPC306365
0.519 Remote Similarity NPC2363
0.519 Remote Similarity NPC479429
0.519 Remote Similarity NPC479314
0.5132 Remote Similarity NPC180006
0.5122 Remote Similarity NPC267336
0.5122 Remote Similarity NPC272650
0.506 Remote Similarity NPC258567
0.5059 Remote Similarity NPC481286

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC20631 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