Natural Product: NPC231134

Natural Product IDNPC231134
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LQXKAIKFJZYCKC-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 158031
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002595] 3'-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 LQXKAIKFJZYCKC-AWEZNQCLSA-N
Standard InCHI InChI=1S/C18H18O6/c1-8-16(21)9(2)18-15(17(8)22)13(20)7-14(24-18)11-6-10(23-3)4-5-12(11)19/h4-6,14,19,21-22H,7H2,1-3H3/t14-/m0/s1
SMILES Cc1c(c(C)c2c(C(=O)C[C@@H](c3cc(ccc3O)OC)O2)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.11 Volume:   328.501
?
Van der Waals volume.
Dense:   1.005 LogP:   2.793
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.69
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.093
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
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:   0.783 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.113 Fsp3:   0.278
MCE-18:   63.478
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.54 Fluc inhibitor:   0.84
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.334
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.323
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.317 Promiscuous compounds:   0.056

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.113 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.241 Pgp-substrate:   0.006
PAMPA:   0.592
?
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):   0.017
20% Bioavailability (F20%):   0.069 30% Bioavailability (F30%):   0.074
50% Bioavailability (F50%):   0.425

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.992
Plasma Protein Binding (PPB):   95.449% Volume Distribution (VD):   0.032
Fu: 4.925%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.897 BCRP inhibitor:   0.076
BSEP inhibitor:   0.838

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.502
CYP2C19-inhibitor:   0.872 CYP2C19-substrate:   0.164
CYP2C9-inhibitor:   0.621 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.937
CYP3A4-inhibitor:   0.991 CYP3A4-substrate:   0.936
CYP2B6-substrate:   0.006 CYP2C8-inhibitor:   0.836
HLM stability:   0.964
?
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):  6.752 Half-life (T1/2):  1.167

ADMET: Toxicity

hERG Blockers:  0.048 hERG Blockers (10um):  0.426
Human Hepatotoxicity (H-HT):  0.72 Drug-induced Liver Injury (DILI):  0.677
AMES Toxicity:  0.755 Rat Oral Acute Toxicity:  0.719
Maximum Recommended Daily Dose:  0.677 Skin Sensitization:  0.837
Carcinogencity:  0.566 Eye Corrosion:  0.04
Eye Irritation:  0.982 Respiratory Toxicity:  0.978
Drug-induced Neurotoxicity:  0.467 Ototoxicity:  0.456
Hematotoxicity:  0.244 Drug-induced Nephrotoxicity:  0.552
Genotoxicity:  0.963 RPMI-8226 Immunitoxicity:  0.227
A549 Cytotoxicity:  0.815 Hek293 Cytotoxicity:  0.559
BCF:   1.277
?
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:   3.884
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.539
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.582
?
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
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. fruit n.a. DOI[10.1016/S0040-4020(01)89039-6]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota leaves n.a. n.a. PMID[15217270]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. whole plant n.a. PMID[16079517]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota root bark n.a. n.a. PMID[16562837]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. fruit n.a. PMID[21028890]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota Rhizomes n.a. n.a. PMID[28984452]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1896 Proteus penneri Species Morganellaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3789 Lyonia formosa Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27945 Cancrinia discoidea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2828 Blaps mucronata Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2828 Blaps mucronata Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4703 Solanum hispidum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO46 Onosma hispida Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1896 Proteus penneri Species Morganellaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27945 Cancrinia discoidea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5638 Garcinia livingstonei Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14359 Pentarhizidium orientale Species Onocleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3789 Lyonia formosa Species Ericaceae 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
NPT1602 Individual protein Neuraminidase Influenza A virus (A/Puerto Rico/8/1934(H1N1)) IC50 = 24500.0 nM PMID[28984452]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT616 Cell line MDCK Canis lupus familiaris CC50 > 100000.0 nM PMID[28984452]
NPT1453 Organism Influenza A virus (A/PR/8/34(H1N1)) Influenza A virus (A/Puerto Rico/8/1934(H1N1)) EC50 = 23000.0 nM PMID[28984452]
NPT2 Others Unspecified n.a. IC50 = 24600.0 nM PMID[28984452]

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 NPC231134 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
0.6852 Remote Similarity NPC324134
0.6852 Remote Similarity NPC40833
0.6667 Remote Similarity NPC296917
0.6667 Remote Similarity NPC170907
0.6379 Remote Similarity NPC270789
0.625 Remote Similarity NPC480995
0.625 Remote Similarity NPC477503
0.6182 Remote Similarity NPC167624
0.6182 Remote Similarity NPC166482
0.6 Remote Similarity NPC248372
0.5965 Remote Similarity NPC192083
0.5167 Remote Similarity NPC485881
0.5085 Remote Similarity NPC4743

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC231134 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
0.5965 Remote Similarity NPD2393 Clinical (unspecified phase)

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