Natural Product: NPC201800

Natural Product IDNPC201800
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-2-(2-(3,7-Dimethylocta-2,6-Dienyl)-3-Hydroxy-4-Methoxyphenyl)-5-Hydroxy-7-Methoxy-6-(3-Methylbut-2-Enyl)Chroman-4-One
IUPAC Name (2S)-2-[2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-4-methoxyphenyl]-5-hydroxy-7-methoxy-6-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462919
PubChem CID 11375844
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003645] 2'-prenylated flavans
            • [CHEMONTID:0003588] 2'-prenylated flavanones

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 XZRKREBZFMXPOX-ODVIPSCOSA-N
Standard InCHI InChI=1S/C32H40O6/c1-19(2)9-8-10-21(5)12-14-23-22(15-16-26(36-6)31(23)34)28-17-25(33)30-29(38-28)18-27(37-7)24(32(30)35)13-11-20(3)4/h9,11-12,15-16,18,28,34-35H,8,10,13-14,17H2,1-7H3/b21-12+/t28-/m0/s1
SMILES CC(=CCC/C(=C/Cc1c(ccc(c1O)OC)[C@@H]1CC(=O)c2c(cc(c(CC=C(C)C)c2O)OC)O1)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   520.28 Volume:   562.735
?
Van der Waals volume.
Dense:   0.925 LogP:   7.715
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.739
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.698
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   21.0
TPSA:   85.22
?
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:   0.314 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.731 Fsp3:   0.406
MCE-18:   71.044
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.996 Fluc inhibitor:   0.585
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.695
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.638
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.457 Promiscuous compounds:   0.179

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.923 MDCK Permeability:   -4.675
Pgp-inhibitor:   1.0 Pgp-substrate:   0.0
PAMPA:   0.001
?
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):   0.017
20% Bioavailability (F20%):   0.766 30% Bioavailability (F30%):   0.992
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.829
Plasma Protein Binding (PPB):   97.208% Volume Distribution (VD):   0.207
Fu: 2.425%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.995
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.722 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.127 CYP2D6-substrate:   0.675
CYP3A4-inhibitor:   0.328 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  4.445 Half-life (T1/2):  1.329

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.52
Human Hepatotoxicity (H-HT):  0.882 Drug-induced Liver Injury (DILI):  0.958
AMES Toxicity:  0.497 Rat Oral Acute Toxicity:  0.9
Maximum Recommended Daily Dose:  0.762 Skin Sensitization:  0.978
Carcinogencity:  0.525 Eye Corrosion:  0.0
Eye Irritation:  0.144 Respiratory Toxicity:  0.988
Drug-induced Neurotoxicity:  0.902 Ototoxicity:  0.824
Hematotoxicity:  0.608 Drug-induced Nephrotoxicity:  0.975
Genotoxicity:  0.983 RPMI-8226 Immunitoxicity:  0.283
A549 Cytotoxicity:  0.889 Hek293 Cytotoxicity:  0.598
BCF:   2.207
?
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:   5.665
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.457
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   7.226
?
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
NPO19369 Bacillus thuringiensis Species Bacillaceae Bacteria n.a. n.a. n.a. PMID[11087590]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. leaf n.a. PMID[11421757]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. PMID[11975480]
NPO10729 Lechevalieria aerocolonigenes Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. PMID[15620255]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota leaves Krachong waterfall area, Trang Province, Thailand 2001-APR PMID[15974621]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. leaf n.a. PMID[15974621]
NPO3453 Elaeocarpus fuscoides Species Elaeocarpaceae Eukaryota leaves n.a. n.a. PMID[17451272]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. leaf n.a. PMID[18844422]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota leaves n.a. n.a. PMID[18844422]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota epidermis of the sclerotia n.a. n.a. PMID[19746919]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. PMID[27808511]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[28972755]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. PMID[8984162]
NPO19369 Bacillus thuringiensis Species Bacillaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO896 Streptomyces kanamyceticus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1209 Swartzia madagascariensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5344 Calodendrum capense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6330 Croton caudatus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3453 Elaeocarpus fuscoides Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15164 Jacobaea adonidifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10729 Lechevalieria aerocolonigenes Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO477 Lepraria xanthina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8543 Meconopsis horridula Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7087 Oxera splendida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3280 Penicillium crustaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12330 Pseudophryne coriacea Species Myobatrachidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5508 Stevia purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO305 Vitex pinnata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8543 Meconopsis horridula Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1209 Swartzia madagascariensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15164 Jacobaea adonidifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3280 Penicillium crustaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10729 Lechevalieria aerocolonigenes Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO19369 Bacillus thuringiensis Species Bacillaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO305 Vitex pinnata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8543 Meconopsis horridula Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23577 Wolfiporia cocos Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1209 Swartzia madagascariensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5508 Stevia purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7087 Oxera splendida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO896 Streptomyces kanamyceticus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO5344 Calodendrum capense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6330 Croton caudatus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12330 Pseudophryne coriacea Species Myobatrachidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO477 Lepraria xanthina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11884 Macaranga tanarius Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3453 Elaeocarpus fuscoides Species Elaeocarpaceae 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
NPT1 Others Radical scavenging activity n.a. IC50 = 413000.0 nM PMID[15974621]

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 NPC201800 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
0.7606 Intermediate Similarity NPC299436
0.6203 Remote Similarity NPC210459
0.6164 Remote Similarity NPC36217
0.6056 Remote Similarity NPC69674
0.575 Remote Similarity NPC67396
0.5647 Remote Similarity NPC321399
0.557 Remote Similarity NPC64915
0.5556 Remote Similarity NPC278778
0.55 Remote Similarity NPC470328
0.55 Remote Similarity NPC209614
0.5422 Remote Similarity NPC45849
0.5422 Remote Similarity NPC195796
0.5375 Remote Similarity NPC213896
0.5366 Remote Similarity NPC226025
0.5309 Remote Similarity NPC164272
0.5309 Remote Similarity NPC470327
0.525 Remote Similarity NPC484416
0.525 Remote Similarity NPC228504
0.5244 Remote Similarity NPC185276
0.5238 Remote Similarity NPC472626
0.5181 Remote Similarity NPC298692
0.5062 Remote Similarity NPC290133

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201800 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