Natural Product: NPC161414

Natural Product IDNPC161414
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OZAXEQSFFWNBNQ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5318626
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0003504] 8-prenylated flavones

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 OZAXEQSFFWNBNQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O6/c1-10(2)3-5-12-14(22)8-16(24)19-17(25)9-18(26-20(12)19)11-4-6-13(21)15(23)7-11/h4,6-9,21-24H,1,3,5H2,2H3
SMILES C=C(C)CCc1c(cc(c2c(=O)cc(c3ccc(c(c3)O)O)oc12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   357.82
?
Van der Waals volume.
Dense:   0.99 LogP:   3.118
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.717
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.539
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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:   0.419 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.825 Fsp3:   0.15
MCE-18:   20.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.917 Fluc inhibitor:   0.457
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.994
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.721
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.179 Promiscuous compounds:   0.104

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.955 MDCK Permeability:   -4.739
Pgp-inhibitor:   0.014 Pgp-substrate:   0.006
PAMPA:   0.023
?
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):   0.006
20% Bioavailability (F20%):   0.668 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.141 MRP1:   0.956
Plasma Protein Binding (PPB):   97.853% Volume Distribution (VD):   -0.421
Fu: 1.688%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.976
BSEP inhibitor:   0.708

ADMET: Metabolism

CYP1A2-inhibitor:   0.29 CYP1A2-substrate:   0.029
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.786 CYP2C9-substrate:   0.063
CYP2D6-inhibitor:   0.981 CYP2D6-substrate:   0.911
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.837
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.91
HLM stability:   0.892
?
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):  7.465 Half-life (T1/2):  1.476

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.617
Human Hepatotoxicity (H-HT):  0.332 Drug-induced Liver Injury (DILI):  0.666
AMES Toxicity:  0.47 Rat Oral Acute Toxicity:  0.353
Maximum Recommended Daily Dose:  0.737 Skin Sensitization:  0.991
Carcinogencity:  0.625 Eye Corrosion:  0.542
Eye Irritation:  0.997 Respiratory Toxicity:  0.891
Drug-induced Neurotoxicity:  0.012 Ototoxicity:  0.239
Hematotoxicity:  0.053 Drug-induced Nephrotoxicity:  0.013
Genotoxicity:  0.857 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.399 Hek293 Cytotoxicity:  0.358
BCF:   1.585
?
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:   4.493
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.541
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.162
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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
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[26081757]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota Fruits n.a. n.a. PMID[26110443]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. aerial part n.a. PMID[27169184]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25004 Heracleum yungningense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25004 Heracleum yungningense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25004 Heracleum yungningense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25004 Heracleum yungningense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17612 Xanthium sibiricum Species Asteraceae 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 NPC161414 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
0.7627 Intermediate Similarity NPC88804
0.6349 Remote Similarity NPC220062
0.597 Remote Similarity NPC216978
0.597 Remote Similarity NPC601414
0.5938 Remote Similarity NPC606140
0.5606 Remote Similarity NPC63187
0.5606 Remote Similarity NPC482025
0.55 Remote Similarity NPC17286
0.5333 Remote Similarity NPC117418
0.5323 Remote Similarity NPC279121
0.5263 Remote Similarity NPC66809
0.5263 Remote Similarity NPC46736
0.5231 Remote Similarity NPC188203
0.5217 Remote Similarity NPC3825
0.5135 Remote Similarity NPC471982
0.5068 Remote Similarity NPC170492
0.5065 Remote Similarity NPC197856

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC161414 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
0.5323 Remote Similarity NPD1511 Phase 2

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