Natural Product: NPC32694

Natural Product IDNPC32694
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cudraxanthone D
IUPAC Name 2,3,8-trihydroxy-6-methoxy-5-(2-methylbut-3-en-2-yl)-1-(3-methylbut-2-enyl)xanthen-9-one
Synonyms Cudratricusxanthone F; Cudraxanthone D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL425926
PubChem CID 11611248
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 UIIGEZZURHDEDK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H26O6/c1-7-24(4,5)20-17(29-6)10-14(25)19-22(28)18-13(9-8-12(2)3)21(27)15(26)11-16(18)30-23(19)20/h7-8,10-11,25-27H,1,9H2,2-6H3
SMILES COc1cc(O)c2c(c1C(C=C)(C)C)oc1c(c2=O)c(CC=C(C)C)c(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   410.17 Volume:   427.004
?
Van der Waals volume.
Dense:   0.961 LogP:   4.748
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.653
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.779
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.309 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.35 Fsp3:   0.292
MCE-18:   24.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.937 Fluc inhibitor:   0.128
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.869
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.882
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.268 Promiscuous compounds:   0.195

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.066 MDCK Permeability:   -4.783
Pgp-inhibitor:   0.766 Pgp-substrate:   0.104
PAMPA:   0.168
?
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):   0.125
20% Bioavailability (F20%):   0.994 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.957
Plasma Protein Binding (PPB):   95.078% Volume Distribution (VD):   0.13
Fu: 4.355%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.999
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.194 CYP2C9-substrate:   0.087
CYP2D6-inhibitor:   0.51 CYP2D6-substrate:   0.954
CYP3A4-inhibitor:   0.76 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):  7.364 Half-life (T1/2):  1.392

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.559
Human Hepatotoxicity (H-HT):  0.408 Drug-induced Liver Injury (DILI):  0.843
AMES Toxicity:  0.503 Rat Oral Acute Toxicity:  0.843
Maximum Recommended Daily Dose:  0.673 Skin Sensitization:  0.943
Carcinogencity:  0.635 Eye Corrosion:  0.027
Eye Irritation:  0.949 Respiratory Toxicity:  0.959
Drug-induced Neurotoxicity:  0.134 Ototoxicity:  0.314
Hematotoxicity:  0.108 Drug-induced Nephrotoxicity:  0.146
Genotoxicity:  0.91 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.39 Hek293 Cytotoxicity:  0.546
BCF:   2.01
?
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:   4.581
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.515
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.762
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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
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16203143]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16919944]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root bark n.a. n.a. PMID[17608532]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[17950599]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota fruits n.a. n.a. PMID[19113968]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[19191562]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[19280148]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19285413]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19660948]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota Root barks n.a. n.a. PMID[25051453]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[25322455]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota root bark Mongolian n.a. PMID[26073007]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root barks purchased from the local herbal market, Chungbuk, Korea 2012-JUL PMID[26227773]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[27420919]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota Aerial Parts n.a. n.a. PMID[31747283]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20471 Sophora alopecuroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8797 Cudrania tricuspidata Species Moraceae 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
NPT1214 Individual protein Acyl coenzyme A:cholesterol acyltransferase 1 Homo sapiens IC50 = 57600.0 nM PMID[18311894]
NPT2584 Individual protein Acyl coenzyme A:cholesterol acyltransferase 2 Homo sapiens IC50 = 75200.0 nM PMID[18316521]
NPT344 Individual protein Sialidase Clostridium perfringens Ki = 143.0 nM PMID[17253859]
NPT344 Individual protein Sialidase Clostridium perfringens Ki = 950.0 nM PMID[17253859]
NPT344 Individual protein Sialidase Clostridium perfringens Ki = 435.9 nM PMID[16724859]
NPT344 Individual protein Sialidase Clostridium perfringens Ki = 2230.0 nM PMID[12444692]
NPT344 Individual protein Sialidase Clostridium perfringens IC50 = 278.0 nM PMID[15026054]
NPT344 Individual protein Sialidase Clostridium perfringens IC50 = 1271.0 nM PMID[8450319]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 16100.0 nM PMID[16165353]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 > 50000.0 nM PMID[27420919]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 4800.0 nM PMID[27420919]
NPT1 Others Radical scavenging activity n.a. IC50 = 17400.0 nM PMID[15711537]
NPT1 Others Radical scavenging activity n.a. IC50 = 92800.0 nM PMID[11325240]
NPT1 Others Radical scavenging activity n.a. IC50 = 25200.0 nM Open TG-GATES in vivo data: Hematology
NPT614 Tissue Plasma Rattus norvegicus IC50 = 6200.0 nM PMID[25978960]
NPT2 Others Unspecified n.a. IC50 = 16200.0 nM PMID[24679044]

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 NPC32694 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
0.7941 Intermediate Similarity NPC478522
0.7536 Intermediate Similarity NPC473286
0.7015 Intermediate Similarity NPC235018
0.6197 Remote Similarity NPC604618
0.6056 Remote Similarity NPC45146
0.5797 Remote Similarity NPC89474
0.5733 Remote Similarity NPC220313
0.5493 Remote Similarity NPC142339
0.5479 Remote Similarity NPC219867
0.5467 Remote Similarity NPC478518
0.5405 Remote Similarity NPC80375
0.5316 Remote Similarity NPC481609
0.525 Remote Similarity NPC329760
0.5181 Remote Similarity NPC481610
0.5176 Remote Similarity NPC479157
0.5128 Remote Similarity NPC478517
0.5065 Remote Similarity NPC479160

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC32694 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