Natural Product: NPC1089

Natural Product IDNPC1089
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-5,7-Dihydroxy-6-Prenylflavanone
IUPAC Name (2S)-5,7-dihydroxy-6-(3-methylbut-2-enyl)-2-phenyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2165236
PubChem CID 6546086
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-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 UOWOIGNEFLTNAW-KRWDZBQOSA-N
Standard InCHI InChI=1S/C20H20O4/c1-12(2)8-9-14-15(21)10-18-19(20(14)23)16(22)11-17(24-18)13-6-4-3-5-7-13/h3-8,10,17,21,23H,9,11H2,1-2H3/t17-/m0/s1
SMILES CC(=CCc1c(cc2c(C(=O)C[C@@H](c3ccccc3)O2)c1O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   324.14 Volume:   342.876
?
Van der Waals volume.
Dense:   0.945 LogP:   4.92
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.857
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.975
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.826 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.061 Fsp3:   0.25
MCE-18:   56.88
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.843 Fluc inhibitor:   0.916
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.592
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.48
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.365 Promiscuous compounds:   0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.955 MDCK Permeability:   -4.735
Pgp-inhibitor:   0.999 Pgp-substrate:   0.003
PAMPA:   0.544
?
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):   0.008
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.962
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.913
Plasma Protein Binding (PPB):   96.904% Volume Distribution (VD):   0.454
Fu: 3.155%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.974
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.306 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.705 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.362 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.25 CYP2D6-substrate:   0.964
CYP3A4-inhibitor:   0.839 CYP3A4-substrate:   0.998
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):  4.556 Half-life (T1/2):  0.994

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.545
Human Hepatotoxicity (H-HT):  0.784 Drug-induced Liver Injury (DILI):  0.32
AMES Toxicity:  0.779 Rat Oral Acute Toxicity:  0.731
Maximum Recommended Daily Dose:  0.564 Skin Sensitization:  0.95
Carcinogencity:  0.34 Eye Corrosion:  0.001
Eye Irritation:  0.966 Respiratory Toxicity:  0.63
Drug-induced Neurotoxicity:  0.83 Ototoxicity:  0.458
Hematotoxicity:  0.163 Drug-induced Nephrotoxicity:  0.892
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.162
A549 Cytotoxicity:  0.554 Hek293 Cytotoxicity:  0.543
BCF:   1.919
?
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:   4.57
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.198
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.501
?
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
NPO27636 Hippasteria phrygiana Species Goniasteridae Eukaryota n.a. pacific n.a. PMID[16252922]
NPO27230 Eysenhardtia platycarpa Species Fabaceae Eukaryota n.a. branch n.a. PMID[17190443]
NPO27230 Eysenhardtia platycarpa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[17190443]
NPO27449 Halichondria okadai Species Halichondriidae Eukaryota n.a. n.a. n.a. PMID[21410164]
NPO40192 Macaranga kurzii Species Euphorbiaceae Eukaryota Leaves n.a. n.a. PMID[23134335]
NPO5702 Brosimum rubescens Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358642]
NPO6854 Podocarpus elongatus Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6740 Amycolatopsis sulphurea Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO27230 Eysenhardtia platycarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9137 Tasmannia lanceolata Species Winteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9899 Ceanothus americanus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7296 Cynometra ananta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27636 Hippasteria phrygiana Species Goniasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5702 Brosimum rubescens Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27837 Sarracenia flava Species Sarraceniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29258 Virola oleifera Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10268 Tessmannia densiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27794 Acritopappus longifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27340 Campylopus clavatus Species Leucobryaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40192 Macaranga kurzii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27594 Viola odorata Species Violaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3193 Derris rariflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27837 Sarracenia flava Species Sarraceniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2463 Anemone rivularis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27837 Sarracenia flava Species Sarraceniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27837 Sarracenia flava Species Sarraceniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9899 Ceanothus americanus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27411 Liparis nakaharai Species Liparidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10268 Tessmannia densiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17250 Schnabelia terniflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2985 Illicium parviflorum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6854 Podocarpus elongatus Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3193 Derris rariflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9137 Tasmannia lanceolata Species Winteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29258 Virola oleifera Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6740 Amycolatopsis sulphurea Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27837 Sarracenia flava Species Sarraceniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27340 Campylopus clavatus Species Leucobryaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5702 Brosimum rubescens Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27636 Hippasteria phrygiana Species Goniasteridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27131 Methylosinus trichosporium Species Methylocystaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27756 Lepidiota negatoria Species Scarabaeidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27230 Eysenhardtia platycarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27074 Dermocybe semisanguinea Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27794 Acritopappus longifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7481 Callicarpa nudiflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27449 Halichondria okadai Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27709 Rhododendron maximum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7296 Cynometra ananta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27211 Adenocarpus hispanicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2463 Anemone rivularis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1497 Capnophyllum peregrinum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27651 Cissus tricuspidata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27194 Conger myriaster Species Congridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27594 Viola odorata Species Violaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27173 Ramalina pollinaria Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4666 Canarium samoense Species Strombidae 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
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus IC50 = 18000.0 nM PMID[23134335]

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 NPC1089 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
0.7759 Intermediate Similarity NPC125855
0.7258 Intermediate Similarity NPC35038
0.7222 Intermediate Similarity NPC482119
0.7222 Intermediate Similarity NPC482120
0.7167 Intermediate Similarity NPC223500
0.7031 Intermediate Similarity NPC228504
0.6923 Remote Similarity NPC64915
0.6885 Remote Similarity NPC166689
0.6833 Remote Similarity NPC95936
0.6727 Remote Similarity NPC312391
0.6716 Remote Similarity NPC185276
0.6667 Remote Similarity NPC213896
0.6567 Remote Similarity NPC488556
0.6562 Remote Similarity NPC223787
0.6515 Remote Similarity NPC290133
0.6471 Remote Similarity NPC472627
0.6377 Remote Similarity NPC226025
0.6377 Remote Similarity NPC278778
0.6377 Remote Similarity NPC298692
0.6324 Remote Similarity NPC470328
0.6324 Remote Similarity NPC209614
0.6324 Remote Similarity NPC164272
0.6324 Remote Similarity NPC470327
0.6286 Remote Similarity NPC472628
0.6232 Remote Similarity NPC261063
0.623 Remote Similarity NPC76372
0.623 Remote Similarity NPC37496
0.6197 Remote Similarity NPC195796
0.6143 Remote Similarity NPC321779
0.6087 Remote Similarity NPC267375
0.6 Remote Similarity NPC228779
0.6 Remote Similarity NPC483811
0.5972 Remote Similarity NPC45849
0.5972 Remote Similarity NPC472626
0.5972 Remote Similarity NPC210459
0.5972 Remote Similarity NPC488557
0.5968 Remote Similarity NPC258630
0.5965 Remote Similarity NPC243083
0.5965 Remote Similarity NPC13768
0.5965 Remote Similarity NPC287246
0.5942 Remote Similarity NPC472629
0.5915 Remote Similarity NPC488558
0.589 Remote Similarity NPC27337
0.5873 Remote Similarity NPC39045
0.5833 Remote Similarity NPC488554
0.5833 Remote Similarity NPC472630
0.5781 Remote Similarity NPC69674
0.5781 Remote Similarity NPC265040
0.5781 Remote Similarity NPC250214
0.5753 Remote Similarity NPC472631
0.5733 Remote Similarity NPC474055
0.5692 Remote Similarity NPC109223
0.5692 Remote Similarity NPC220998
0.5692 Remote Similarity NPC10937
0.569 Remote Similarity NPC204515
0.5658 Remote Similarity NPC472634
0.5658 Remote Similarity NPC293319
0.5625 Remote Similarity NPC39329
0.5625 Remote Similarity NPC51032
0.56 Remote Similarity NPC488555
0.56 Remote Similarity NPC484418
0.5593 Remote Similarity NPC150648
0.5522 Remote Similarity NPC608140
0.55 Remote Similarity NPC255106
0.55 Remote Similarity NPC194432
0.55 Remote Similarity NPC235165
0.55 Remote Similarity NPC324386
0.5455 Remote Similarity NPC17170
0.5455 Remote Similarity NPC610133
0.5385 Remote Similarity NPC13575
0.5373 Remote Similarity NPC106976
0.5362 Remote Similarity NPC470890
0.5333 Remote Similarity NPC37392
0.5303 Remote Similarity NPC187282
0.5303 Remote Similarity NPC175504
0.5263 Remote Similarity NPC472598
0.5246 Remote Similarity NPC110776
0.5231 Remote Similarity NPC143896
0.5224 Remote Similarity NPC176229
0.5224 Remote Similarity NPC470135
0.52 Remote Similarity NPC316960
0.52 Remote Similarity NPC317715
0.52 Remote Similarity NPC78835
0.52 Remote Similarity NPC148945
0.52 Remote Similarity NPC309512
0.52 Remote Similarity NPC204561
0.5156 Remote Similarity NPC259685
0.5152 Remote Similarity NPC107572
0.5152 Remote Similarity NPC32739
0.5147 Remote Similarity NPC285555
0.5147 Remote Similarity NPC76338
0.5147 Remote Similarity NPC250242
0.5143 Remote Similarity NPC200761
0.5135 Remote Similarity NPC58805
0.5085 Remote Similarity NPC265871
0.5085 Remote Similarity NPC205093
0.5082 Remote Similarity NPC177354
0.5075 Remote Similarity NPC221432
0.5075 Remote Similarity NPC257097
0.5075 Remote Similarity NPC148757
0.5067 Remote Similarity NPC97812
0.5067 Remote Similarity NPC600145
0.5067 Remote Similarity NPC605490
0.5067 Remote Similarity NPC605492

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC1089 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
0.5965 Remote Similarity NPD1550 Phase 2

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