Natural Product: NPC25675

Natural Product IDNPC25675
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ICUTWTIGUGEDEI-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5321057
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated 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 ICUTWTIGUGEDEI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H14O7/c1-21-15-7-14-16(17(20)18(15)22-2)10(19)6-12(25-14)9-3-4-11-13(5-9)24-8-23-11/h3-7,20H,8H2,1-2H3
SMILES COc1cc2c(c(=O)cc(c3ccc4c(c3)OCO4)o2)c(c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.07 Volume:   326.098
?
Van der Waals volume.
Dense:   1.049 LogP:   2.884
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.751
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.67
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   87.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.783 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.415 Fsp3:   0.167
MCE-18:   46.095
?
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:   0.421 Fluc inhibitor:   0.909
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.955
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.657
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.148 Promiscuous compounds:   0.432

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.971 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.944 Pgp-substrate:   0.03
PAMPA:   0.077
?
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):   0.002
20% Bioavailability (F20%):   0.051 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.39 MRP1:   0.916
Plasma Protein Binding (PPB):   97.995% Volume Distribution (VD):   -0.31
Fu: 1.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.901
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.839 CYP1A2-substrate:   0.875
CYP2C19-inhibitor:   0.43 CYP2C19-substrate:   0.038
CYP2C9-inhibitor:   0.965 CYP2C9-substrate:   0.924
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.249
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.122
HLM stability:   0.265
?
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):  3.374 Half-life (T1/2):  1.108

ADMET: Toxicity

hERG Blockers:  0.116 hERG Blockers (10um):  0.451
Human Hepatotoxicity (H-HT):  0.458 Drug-induced Liver Injury (DILI):  0.846
AMES Toxicity:  0.578 Rat Oral Acute Toxicity:  0.466
Maximum Recommended Daily Dose:  0.651 Skin Sensitization:  0.487
Carcinogencity:  0.849 Eye Corrosion:  0.441
Eye Irritation:  0.979 Respiratory Toxicity:  0.734
Drug-induced Neurotoxicity:  0.248 Ototoxicity:  0.134
Hematotoxicity:  0.331 Drug-induced Nephrotoxicity:  0.156
Genotoxicity:  0.761 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.472
BCF:   1.34
?
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:   3.717
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.851
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.227
?
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
NPO19975 Pycnandra acuminata Species Sapotaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.phytochem.2007.07.001]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota seeds n.a. n.a. PMID[12762787]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12762809]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota root n.a. n.a. PMID[15921428]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. leaf n.a. PMID[8699184]
NPO8129 Inocybe geophylla Species Inocybaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11339 Litsea salicifolia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12828 Dysidea tupha Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1695 Monascus pilosus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7874 Helichrysum lepidissimum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5534 Alternaria kikuchiana Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8609 Hopea utilis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO218 Acer carpinifolium Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11506 Stipa vaseyi Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26095 Hypericum revolutum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5534 Alternaria kikuchiana Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19975 Pycnandra acuminata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1695 Monascus pilosus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12118 Cleistopholis staudtii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11339 Litsea salicifolia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6861 Galium dasypodum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12602 Leuzea centauroides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO940 Vernonia anisochaetoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12828 Dysidea tupha Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4759 Helleborus multifidus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10970 Osmorhiza aristata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8129 Inocybe geophylla Species Inocybaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7874 Helichrysum lepidissimum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4322 Scabiosa succisa Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8609 Hopea utilis Species Dipterocarpaceae 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

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 NPC25675 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
0.8364 Intermediate Similarity NPC69394
0.7377 Intermediate Similarity NPC76482
0.7368 Intermediate Similarity NPC145379
0.7321 Intermediate Similarity NPC75279
0.7 Intermediate Similarity NPC160951
0.6897 Remote Similarity NPC239128
0.6885 Remote Similarity NPC47781
0.678 Remote Similarity NPC120163
0.678 Remote Similarity NPC276409
0.6721 Remote Similarity NPC608539
0.6667 Remote Similarity NPC25270
0.6667 Remote Similarity NPC605634
0.629 Remote Similarity NPC255350
0.619 Remote Similarity NPC283600
0.619 Remote Similarity NPC195202
0.6133 Remote Similarity NPC609451
0.6129 Remote Similarity NPC163780
0.6032 Remote Similarity NPC176300
0.5938 Remote Similarity NPC2476
0.5735 Remote Similarity NPC99671
0.5692 Remote Similarity NPC12200
0.5672 Remote Similarity NPC485299
0.5625 Remote Similarity NPC49824
0.56 Remote Similarity NPC58053
0.5571 Remote Similarity NPC41853
0.5538 Remote Similarity NPC183597
0.5493 Remote Similarity NPC213622
0.5484 Remote Similarity NPC333230
0.5469 Remote Similarity NPC33265
0.5469 Remote Similarity NPC110070
0.5455 Remote Similarity NPC93376
0.5397 Remote Similarity NPC607530
0.5312 Remote Similarity NPC113089
0.5312 Remote Similarity NPC215932
0.5312 Remote Similarity NPC156222
0.5312 Remote Similarity NPC29353
0.5256 Remote Similarity NPC186807
0.525 Remote Similarity NPC605067
0.5231 Remote Similarity NPC57030
0.5224 Remote Similarity NPC25495
0.5224 Remote Similarity NPC104459
0.5224 Remote Similarity NPC177298
0.5224 Remote Similarity NPC604422
0.5156 Remote Similarity NPC250822
0.5152 Remote Similarity NPC256283
0.5147 Remote Similarity NPC279930
0.5147 Remote Similarity NPC131557
0.5143 Remote Similarity NPC603082
0.5075 Remote Similarity NPC212678
0.5075 Remote Similarity NPC83508
0.5072 Remote Similarity NPC227192
0.507 Remote Similarity NPC269906
0.5067 Remote Similarity NPC280493
0.5067 Remote Similarity NPC604322

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC25675 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
0.629 Remote Similarity NPD2801 Pre-clinical

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