Natural Product: NPC40833

Natural Product IDNPC40833
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-2'-Hydroxydemethoxymatteucinol
IUPAC Name (2S)-5,7-dihydroxy-2-(2-hydroxyphenyl)-6,8-dimethyl-2,3-dihydrochromen-4-one
Synonyms (2S)-2'-Hydroxydemethoxymatteucinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1802147
PubChem CID 157103
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] 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 WOGYXYDORXIAGE-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C17H16O5/c1-8-15(20)9(2)17-14(16(8)21)12(19)7-13(22-17)10-5-3-4-6-11(10)18/h3-6,13,18,20-21H,7H2,1-2H3/t13-/m0/s1
SMILES Oc1ccccc1[C@@H]1CC(=O)c2c(O1)c(C)c(c(c2O)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   2.988
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.918
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.261
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.753 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.076 Fsp3:   0.235
MCE-18:   60.619
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.587 Fluc inhibitor:   0.692
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.318
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.29
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.346 Promiscuous compounds:   0.039

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.959 MDCK Permeability:   -4.744
Pgp-inhibitor:   0.898 Pgp-substrate:   0.016
PAMPA:   0.877
?
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):   0.009
20% Bioavailability (F20%):   0.019 30% Bioavailability (F30%):   0.328
50% Bioavailability (F50%):   0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.04 MRP1:   0.995
Plasma Protein Binding (PPB):   96.76% Volume Distribution (VD):   -0.078
Fu: 3.242%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.265
BSEP inhibitor:   0.894

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.73
CYP2C19-inhibitor:   0.206 CYP2C19-substrate:   0.497
CYP2C9-inhibitor:   0.879 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.552 CYP2D6-substrate:   0.772
CYP3A4-inhibitor:   0.868 CYP3A4-substrate:   0.966
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.442
HLM stability:   0.985
?
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):  6.023 Half-life (T1/2):  1.059

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.438
Human Hepatotoxicity (H-HT):  0.75 Drug-induced Liver Injury (DILI):  0.12
AMES Toxicity:  0.681 Rat Oral Acute Toxicity:  0.592
Maximum Recommended Daily Dose:  0.576 Skin Sensitization:  0.941
Carcinogencity:  0.391 Eye Corrosion:  0.038
Eye Irritation:  0.997 Respiratory Toxicity:  0.517
Drug-induced Neurotoxicity:  0.512 Ototoxicity:  0.347
Hematotoxicity:  0.133 Drug-induced Nephrotoxicity:  0.488
Genotoxicity:  0.939 RPMI-8226 Immunitoxicity:  0.177
A549 Cytotoxicity:  0.564 Hek293 Cytotoxicity:  0.514
BCF:   1.182
?
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:   3.888
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.449
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.643
?
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
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. fruit n.a. DOI[10.1016/S0040-4020(01)89039-6]
NPO3791 Lentinus edodes Species Omphalotaceae Eukaryota n.a. n.a. n.a. PMID[15055237]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota leaves n.a. n.a. PMID[15217270]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. whole plant n.a. PMID[16079517]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota root bark n.a. n.a. PMID[16562837]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. fruit n.a. PMID[21028890]
NPO25983 Pisonia aculeata Species Nyctaginaceae Eukaryota n.a. n.a. n.a. PMID[21542597]
NPO25983 Pisonia aculeata Species Nyctaginaceae Eukaryota n.a. stem n.a. PMID[21542597]
NPO25983 Pisonia aculeata Species Nyctaginaceae Eukaryota n.a. root n.a. PMID[21542597]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota Rhizomes n.a. n.a. PMID[28984452]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. PMID[33264011]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO25983 Pisonia aculeata Species Nyctaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11078 Tricholoma matsutake Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2828 Blaps mucronata Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27945 Cancrinia discoidea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3789 Lyonia formosa Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1896 Proteus penneri Species Morganellaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3791 Lentinus edodes Species Omphalotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. Database[FooDB]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11078 Tricholoma matsutake Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3791 Lentinus edodes Species Omphalotaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11078 Tricholoma matsutake Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26657 Conocephalum conicum Species Conocephalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3789 Lyonia formosa Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25983 Pisonia aculeata Species Nyctaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3791 Lentinus edodes Species Omphalotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27945 Cancrinia discoidea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1896 Proteus penneri Species Morganellaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20898 Agaricus bisporus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2828 Blaps mucronata Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11078 Tricholoma matsutake Species Tricholomataceae 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
NPT1602 Individual protein Neuraminidase Influenza A virus (A/Puerto Rico/8/1934(H1N1)) IC50 = 23900.0 nM PMID[28984452]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT616 Cell line MDCK Canis lupus familiaris CC50 > 100000.0 nM PMID[28984452]
NPT790 Organism Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis H37Rv MIC = 20.0 ug.mL-1 PMID[21542597]

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 NPC40833 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 NPC324134
0.7551 Intermediate Similarity NPC4743
0.7347 Intermediate Similarity NPC248372
0.6863 Remote Similarity NPC167624
0.6863 Remote Similarity NPC166482
0.6852 Remote Similarity NPC231134
0.6604 Remote Similarity NPC192083
0.6415 Remote Similarity NPC296917
0.6415 Remote Similarity NPC170907
0.6 Remote Similarity NPC480995
0.6 Remote Similarity NPC477503
0.5818 Remote Similarity NPC107586
0.5818 Remote Similarity NPC110776
0.5818 Remote Similarity NPC110038
0.5667 Remote Similarity NPC306829
0.5593 Remote Similarity NPC270789
0.5556 Remote Similarity NPC213322
0.5439 Remote Similarity NPC485881
0.5345 Remote Similarity NPC2416
0.5263 Remote Similarity NPC215885
0.5217 Remote Similarity NPC67805
0.5179 Remote Similarity NPC603284
0.5088 Remote Similarity NPC312391
0.5085 Remote Similarity NPC271590
0.5079 Remote Similarity NPC122894
0.5079 Remote Similarity NPC3642
0.5077 Remote Similarity NPC20488
0.5075 Remote Similarity NPC81697
0.5075 Remote Similarity NPC485615

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC40833 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
0.6604 Remote Similarity NPD2393 Clinical (unspecified phase)

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