Natural Product: NPC43000

Natural Product IDNPC43000
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UBQQOJDZHPQINO-BURNTYAHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1651070
PubChem CID 50900511
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 UBQQOJDZHPQINO-BURNTYAHSA-N
Standard InCHI InChI=1S/C21H30O3/c1-13(2)15-10-14-6-7-18-20(3)8-5-9-21(18,16(14)11-17(15)22)19(23-4)24-12-20/h10-11,13,18-19,22H,5-9,12H2,1-4H3/t18-,19-,20+,21-/m0/s1
SMILES CC(C)c1cc2CC[C@H]3[C@]4(C)CCC[C@@]3(c2cc1O)[C@@H](OC)OC4

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.22 Volume:   356.008
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Van der Waals volume.
Dense:   0.928 LogP:   3.377
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.158
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.457
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.867 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.017 Fsp3:   0.714
MCE-18:   88.889
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.325 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.15
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.347 Promiscuous compounds:   0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.877 MDCK Permeability:   -4.903
Pgp-inhibitor:   0.474 Pgp-substrate:   0.032
PAMPA:   0.051
?
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):   0.0
20% Bioavailability (F20%):   0.163 30% Bioavailability (F30%):   0.299
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.494
Plasma Protein Binding (PPB):   93.993% Volume Distribution (VD):   0.737
Fu: 5.679%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.146
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.028
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.003
HLM stability:   0.092
?
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):  11.47 Half-life (T1/2):  1.048

ADMET: Toxicity

hERG Blockers:  0.144 hERG Blockers (10um):  0.568
Human Hepatotoxicity (H-HT):  0.789 Drug-induced Liver Injury (DILI):  0.285
AMES Toxicity:  0.683 Rat Oral Acute Toxicity:  0.722
Maximum Recommended Daily Dose:  0.826 Skin Sensitization:  0.649
Carcinogencity:  0.571 Eye Corrosion:  0.002
Eye Irritation:  0.752 Respiratory Toxicity:  0.767
Drug-induced Neurotoxicity:  0.167 Ototoxicity:  0.687
Hematotoxicity:  0.242 Drug-induced Nephrotoxicity:  0.636
Genotoxicity:  0.642 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.258 Hek293 Cytotoxicity:  0.35
BCF:   2.299
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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:   4.694
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.808
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.399
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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
NPO30984 Fraxinus sieboldiana Species Oleaceae Eukaryota stem bark n.a. n.a. PMID[17461599]
NPO30984 Fraxinus sieboldiana Species Oleaceae Eukaryota n.a. stem n.a. PMID[20961093]
NPO30984 Fraxinus sieboldiana Species Oleaceae Eukaryota Stem bark Lu Mountain, Jiangxi Province, China 2004-AUG PMID[20961093]
NPO30984 Fraxinus sieboldiana Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[26697686]
NPO30984 Fraxinus sieboldiana Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT179 Cell line A2780 Homo sapiens IC50 > 10000.0 nM PMID[20961093]
NPT180 Cell line HCT-8 Homo sapiens IC50 > 10000.0 nM PMID[20961093]
NPT181 Cell line Bel-7402 Homo sapiens IC50 > 10000.0 nM PMID[20961093]
NPT547 Cell line BGC-823 Homo sapiens IC50 > 10000.0 nM PMID[20961093]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[20961093]

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 NPC43000 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
1.0 High Similarity NPC100414
0.8929 High Similarity NPC108164
0.6406 Remote Similarity NPC49742
0.6364 Remote Similarity NPC321086
0.6269 Remote Similarity NPC100242
0.6154 Remote Similarity NPC321822
0.5692 Remote Similarity NPC58560
0.5574 Remote Similarity NPC260323
0.5556 Remote Similarity NPC11250
0.5469 Remote Similarity NPC137750
0.5312 Remote Similarity NPC172219
0.5312 Remote Similarity NPC192948
0.5312 Remote Similarity NPC304510
0.5312 Remote Similarity NPC35797

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC43000 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