Natural Product: NPC242414

Natural Product IDNPC242414
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OCYZJBDJUYIHMM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11553272
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:0003518] 4-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 OCYZJBDJUYIHMM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H24O6/c1-12(2)6-7-14-17(28-5)11-16(25)18-19(26)15-10-13-8-9-24(3,4)30-21(13)20(27)23(15)29-22(14)18/h6,8-11,25,27H,7H2,1-5H3
SMILES CC(=CCc1c(cc(c2c(=O)c3cc4C=CC(C)(C)Oc4c(c3oc12)O)O)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   408.16 Volume:   418.447
?
Van der Waals volume.
Dense:   0.975 LogP:   5.265
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.026
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.666
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.465 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.325 Fsp3:   0.292
MCE-18:   55.742
?
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:   0
Colloidal aggregators:   0.904 Fluc inhibitor:   0.46
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.871
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.853
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.22 Promiscuous compounds:   0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.023 MDCK Permeability:   -4.672
Pgp-inhibitor:   0.881 Pgp-substrate:   0.124
PAMPA:   0.113
?
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):   0.036
20% Bioavailability (F20%):   0.346 30% Bioavailability (F30%):   0.885
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.205 MRP1:   0.716
Plasma Protein Binding (PPB):   94.232% Volume Distribution (VD):   0.19
Fu: 4.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.878 BCRP inhibitor:   0.93
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.091
CYP3A4-inhibitor:   0.406 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 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):  5.365 Half-life (T1/2):  1.166

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.494
Human Hepatotoxicity (H-HT):  0.592 Drug-induced Liver Injury (DILI):  0.918
AMES Toxicity:  0.681 Rat Oral Acute Toxicity:  0.862
Maximum Recommended Daily Dose:  0.688 Skin Sensitization:  0.754
Carcinogencity:  0.738 Eye Corrosion:  0.0
Eye Irritation:  0.409 Respiratory Toxicity:  0.886
Drug-induced Neurotoxicity:  0.224 Ototoxicity:  0.364
Hematotoxicity:  0.349 Drug-induced Nephrotoxicity:  0.396
Genotoxicity:  0.891 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.206 Hek293 Cytotoxicity:  0.443
BCF:   1.984
?
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:   4.749
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.776
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.033
?
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
NPO5276 Zanthoxylum decaryi Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(74)80113-5]
NPO6775 Cistanche salsa Species Orobanchaceae Eukaryota n.a. whole plant n.a. PMID[10361686]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota Leaves n.a. n.a. PMID[14695790]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota Twigs n.a. n.a. PMID[16124764]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[16724839]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[19113969]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota leaves Bobai, Guangxi Province, China 2005-Dec PMID[24679044]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota Barks n.a. n.a. PMID[24754786]
NPO6775 Cistanche salsa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10228 Ascochyta viciae Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6948 Davidsoniella virescens Species Ceratocystidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2812 Lecanora kukunorensis Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1154 Neomeris annulata Species Dasycladaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9298 Piper wightii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15242 Setosphaeria holmii Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26341 Trifolium resupinatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5276 Zanthoxylum decaryi Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5276 Zanthoxylum decaryi Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6775 Cistanche salsa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6775 Cistanche salsa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5276 Zanthoxylum decaryi Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6775 Cistanche salsa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10228 Ascochyta viciae Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1154 Neomeris annulata Species Dasycladaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11471 Garcinia oblongifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6948 Davidsoniella virescens Species Ceratocystidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15242 Setosphaeria holmii Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9298 Piper wightii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5276 Zanthoxylum decaryi Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26341 Trifolium resupinatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2812 Lecanora kukunorensis Species Lecanoraceae 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 NPC242414 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
0.7571 Intermediate Similarity NPC603436
0.6533 Remote Similarity NPC218313
0.6216 Remote Similarity NPC16492
0.6164 Remote Similarity NPC133970
0.6053 Remote Similarity NPC606144
0.5714 Remote Similarity NPC603548
0.5625 Remote Similarity NPC482612
0.557 Remote Similarity NPC38219
0.557 Remote Similarity NPC234644
0.5556 Remote Similarity NPC288813
0.5301 Remote Similarity NPC482611
0.525 Remote Similarity NPC29876
0.5244 Remote Similarity NPC204879
0.5244 Remote Similarity NPC83922
0.5244 Remote Similarity NPC95842
0.5185 Remote Similarity NPC103238
0.5128 Remote Similarity NPC275122
0.5128 Remote Similarity NPC5322

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC242414 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