Natural Product: NPC229632

Natural Product IDNPC229632
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XMZHFNRJGBRHGV-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3421660
PubChem CID n.a.
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 XMZHFNRJGBRHGV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H26O6/c1-13(2)7-8-15-20-17(12-19(28-5)24(15)29-6)30-18-11-16-14(9-10-25(3,4)31-16)22(26)21(18)23(20)27/h7,9-12,26H,8H2,1-6H3
SMILES COc1cc2oc3cc4OC(C)(C)C=Cc4c(c3c(=O)c2c(c1OC)CC=C(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.17 Volume:   435.743
?
Van der Waals volume.
Dense:   0.969 LogP:   5.585
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.141
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.815
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.45 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.199 Fsp3:   0.32
MCE-18:   55.636
?
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:   0.867 Fluc inhibitor:   0.411
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.805
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.855
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.209 Promiscuous compounds:   0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.005 MDCK Permeability:   -4.653
Pgp-inhibitor:   0.998 Pgp-substrate:   0.01
PAMPA:   0.057
?
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):   0.034
20% Bioavailability (F20%):   0.95 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.982
Plasma Protein Binding (PPB):   96.236% Volume Distribution (VD):   0.194
Fu: 3.177%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.999
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.022 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.252
CYP3A4-inhibitor:   0.966 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):  4.991 Half-life (T1/2):  0.861

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.511
Human Hepatotoxicity (H-HT):  0.459 Drug-induced Liver Injury (DILI):  0.781
AMES Toxicity:  0.622 Rat Oral Acute Toxicity:  0.821
Maximum Recommended Daily Dose:  0.578 Skin Sensitization:  0.802
Carcinogencity:  0.796 Eye Corrosion:  0.003
Eye Irritation:  0.71 Respiratory Toxicity:  0.928
Drug-induced Neurotoxicity:  0.227 Ototoxicity:  0.278
Hematotoxicity:  0.226 Drug-induced Nephrotoxicity:  0.397
Genotoxicity:  0.673 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.176 Hek293 Cytotoxicity:  0.486
BCF:   2.191
?
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:   4.704
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.778
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.959
?
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
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota n.a. n.a. n.a. DOI[10.1071/CH03175]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota twigs n.a. n.a. PMID[20058933]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota young fruits Khokkhon, Tha Bo District, Nong Khai Province, Thailand 2011-Aug PMID[25651042]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota flowers Pakook, Muang District, Chiang Rai Province, Thailand 2013-Feb PMID[25651042]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota Leaves n.a. n.a. PMID[31860303]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25472 Garcinia cowa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25472 Garcinia cowa Species Clusiaceae 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
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 64.0 ug.mL-1 PMID[8759172]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 128.0 ug.mL-1 PMID[10775402]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 128.0 ug.mL-1 PMID[15921415]
NPT19 Organism Escherichia coli Escherichia coli MIC > 128.0 ug.mL-1 PMID[11170656]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 128.0 ug.mL-1 PMID[26317881]
NPT2 Others Unspecified n.a. Inhibition = 62.2 % PMID[22934537]
NPT2 Others Unspecified n.a. IC50 = 26200.0 nM PMID[23558238]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 128.0 ug.mL-1 PMID[25978960]

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 NPC229632 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
0.7826 Intermediate Similarity NPC472450
0.7826 Intermediate Similarity NPC275780
0.7273 Intermediate Similarity NPC165977
0.7083 Intermediate Similarity NPC207690
0.6944 Remote Similarity NPC178964
0.6857 Remote Similarity NPC474186
0.6709 Remote Similarity NPC39091
0.6622 Remote Similarity NPC471973
0.662 Remote Similarity NPC475886
0.6533 Remote Similarity NPC83922
0.6438 Remote Similarity NPC474350
0.6429 Remote Similarity NPC602307
0.6338 Remote Similarity NPC166054
0.6267 Remote Similarity NPC474287
0.6267 Remote Similarity NPC475883
0.6267 Remote Similarity NPC474187
0.6111 Remote Similarity NPC479166
0.6104 Remote Similarity NPC474351
0.6026 Remote Similarity NPC239752
0.5976 Remote Similarity NPC472449
0.5946 Remote Similarity NPC479165
0.589 Remote Similarity NPC101957
0.5867 Remote Similarity NPC70272
0.5658 Remote Similarity NPC16492
0.56 Remote Similarity NPC6633
0.56 Remote Similarity NPC200246
0.5541 Remote Similarity NPC14353
0.5541 Remote Similarity NPC56085
0.5493 Remote Similarity NPC473076
0.5375 Remote Similarity NPC236521
0.5366 Remote Similarity NPC472448
0.5309 Remote Similarity NPC117854
0.5301 Remote Similarity NPC78803
0.525 Remote Similarity NPC23298
0.5185 Remote Similarity NPC184755
0.5185 Remote Similarity NPC152659
0.5125 Remote Similarity NPC184547
0.5122 Remote Similarity NPC170245
0.5116 Remote Similarity NPC484041
0.5067 Remote Similarity NPC255133
0.5065 Remote Similarity NPC97716
0.5065 Remote Similarity NPC265932
0.5065 Remote Similarity NPC604618
0.5063 Remote Similarity NPC59739
0.5062 Remote Similarity NPC189473
0.506 Remote Similarity NPC233502

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC229632 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