Natural Product: NPC100123

Natural Product IDNPC100123
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cratoxyarborenone B
IUPAC Name 1,3,5,7-tetrahydroxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one
Synonyms cratoxyarborenone B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465407
PubChem CID 10475842
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones
                • [CHEMONTID:0003519] 8-prenylated xanthones

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 AVGUAOZYPIBDIZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H24O6/c1-11(2)5-7-13-15(24)9-17(26)23-19(13)22(28)20-18(29-23)10-16(25)14(21(20)27)8-6-12(3)4/h5-6,9-10,24-27H,7-8H2,1-4H3
SMILES CC(=CCc1c(cc(c2c1c(=O)c1c(cc(c(CC=C(C)C)c1O)O)o2)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   396.16 Volume:   409.708
?
Van der Waals volume.
Dense:   0.967 LogP:   4.318
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.443
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.062
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.373 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.255 Fsp3:   0.261
MCE-18:   22.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.947 Fluc inhibitor:   0.627
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.984
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.678
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.408 Promiscuous compounds:   0.285

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.141 MDCK Permeability:   -4.759
Pgp-inhibitor:   0.806 Pgp-substrate:   0.122
PAMPA:   0.32
?
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):   0.275
20% Bioavailability (F20%):   0.981 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.944
Plasma Protein Binding (PPB):   93.357% Volume Distribution (VD):   0.366
Fu: 7.858%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.945 BCRP inhibitor:   0.994
BSEP inhibitor:   0.65

ADMET: Metabolism

CYP1A2-inhibitor:   0.021 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.017 CYP2C9-substrate:   0.248
CYP2D6-inhibitor:   0.934 CYP2D6-substrate:   0.781
CYP3A4-inhibitor:   0.344 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):  1.968 Half-life (T1/2):  1.741

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.501
Human Hepatotoxicity (H-HT):  0.497 Drug-induced Liver Injury (DILI):  0.821
AMES Toxicity:  0.785 Rat Oral Acute Toxicity:  0.906
Maximum Recommended Daily Dose:  0.672 Skin Sensitization:  0.977
Carcinogencity:  0.564 Eye Corrosion:  0.001
Eye Irritation:  0.838 Respiratory Toxicity:  0.988
Drug-induced Neurotoxicity:  0.054 Ototoxicity:  0.258
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.344
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.555 Hek293 Cytotoxicity:  0.736
BCF:   2.128
?
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:   4.963
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.477
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.999
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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
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. leaf n.a. PMID[11908969]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. stem n.a. PMID[11908969]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. twig n.a. PMID[11908969]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. tuberous root n.a. PMID[21650157]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota roots Daba desert reserve (50 km South of Amman), Jordan 2009-APR PMID[21650157]
NPO13263 Verbena brasiliensis Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6106 Hymeniacidon perlevis Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17438 Polygala virgata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18657 Galanthus gracilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18005 Artemisia leucodes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11770 Amphicome emodi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO14950 Ardisia polycephala Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18995 Gaultheria itoana Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19359 Parmotrema delicatulum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19560 Populus italica Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19501 Pseudosuberites hyalinus Species Suberitidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. Database[FooDB]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO11770 Amphicome emodi n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14950 Ardisia polycephala Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6106 Hymeniacidon perlevis Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18995 Gaultheria itoana Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17438 Polygala virgata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19560 Populus italica Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18657 Galanthus gracilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18005 Artemisia leucodes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19359 Parmotrema delicatulum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13263 Verbena brasiliensis Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19501 Pseudosuberites hyalinus Species Suberitidae 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
NPT91 Cell line KB Homo sapiens EC50 = 1.0 ug.mL-1 PMID[11908969]

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 NPC100123 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
0.8361 Intermediate Similarity NPC320359
0.7414 Intermediate Similarity NPC274730
0.6833 Remote Similarity NPC142339
0.6613 Remote Similarity NPC119224
0.6418 Remote Similarity NPC136674
0.6032 Remote Similarity NPC186397
0.5909 Remote Similarity NPC228785
0.5909 Remote Similarity NPC602307
0.5857 Remote Similarity NPC236796
0.5735 Remote Similarity NPC217677
0.5652 Remote Similarity NPC236132
0.5652 Remote Similarity NPC68093
0.5574 Remote Similarity NPC602367
0.5417 Remote Similarity NPC25152
0.5417 Remote Similarity NPC227337
0.5342 Remote Similarity NPC189473
0.5342 Remote Similarity NPC61010
0.5286 Remote Similarity NPC235448
0.527 Remote Similarity NPC218313
0.5217 Remote Similarity NPC45146
0.52 Remote Similarity NPC37870
0.5143 Remote Similarity NPC268204
0.5132 Remote Similarity NPC40491
0.5132 Remote Similarity NPC278052
0.5075 Remote Similarity NPC114377
0.5072 Remote Similarity NPC55832

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC100123 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