Natural Product: NPC228385

Natural Product IDNPC228385
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ODFCWXVQZAQDSO-NLWGTHIKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10913694
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 ODFCWXVQZAQDSO-NLWGTHIKSA-N
Standard InCHI InChI=1S/C20H30O2/c1-12(2)14-10-13-6-7-17-19(3,4)18(22)8-9-20(17,5)15(13)11-16(14)21/h10-12,17-18,21-22H,6-9H2,1-5H3/t17-,18+,20+/m0/s1
SMILES CC(C)c1cc2CC[C@H]3C(C)(C)[C@@H](CC[C@]3(C)c2cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   338.478
?
Van der Waals volume.
Dense:   0.893 LogP:   3.763
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.457
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.061
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   16.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.801 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.583 Fsp3:   0.7
MCE-18:   76.353
?
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:   0.299 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.086
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.472 Promiscuous compounds:   0.044

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.645 MDCK Permeability:   -4.596
Pgp-inhibitor:   0.979 Pgp-substrate:   0.118
PAMPA:   0.1
?
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%):   0.783 30% Bioavailability (F30%):   0.704
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.968
Plasma Protein Binding (PPB):   94.399% Volume Distribution (VD):   0.253
Fu: 6.927%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.104
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.915 CYP1A2-substrate:   0.331
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.288
CYP2C9-inhibitor:   0.325 CYP2C9-substrate:   0.197
CYP2D6-inhibitor:   0.295 CYP2D6-substrate:   0.058
CYP3A4-inhibitor:   0.977 CYP3A4-substrate:   0.116
CYP2B6-substrate:   0.043 CYP2C8-inhibitor:   0.877
HLM stability:   0.643
?
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):  11.765 Half-life (T1/2):  1.406

ADMET: Toxicity

hERG Blockers:  0.051 hERG Blockers (10um):  0.374
Human Hepatotoxicity (H-HT):  0.516 Drug-induced Liver Injury (DILI):  0.082
AMES Toxicity:  0.411 Rat Oral Acute Toxicity:  0.479
Maximum Recommended Daily Dose:  0.729 Skin Sensitization:  0.84
Carcinogencity:  0.681 Eye Corrosion:  0.009
Eye Irritation:  0.867 Respiratory Toxicity:  0.843
Drug-induced Neurotoxicity:  0.052 Ototoxicity:  0.749
Hematotoxicity:  0.34 Drug-induced Nephrotoxicity:  0.734
Genotoxicity:  0.171 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.346 Hek293 Cytotoxicity:  0.391
BCF:   1.75
?
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:   4.117
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.341
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.858
?
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
NPO19645 Chironia krebsii Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(91)80080-K]
NPO16538 Stylophorum diphyllum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO18135 Clausena vestita Species Rutaceae Eukaryota whole plants Yunnan Province, China 2008-JAN PMID[22093759]
NPO12583 Sauromatum giganteum Species Araceae Eukaryota n.a. n.a. n.a. PMID[28394604]
NPO16703 Isodon lophanthoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16538 Stylophorum diphyllum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18319 Fraxinus japonica Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16538 Stylophorum diphyllum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18319 Fraxinus japonica Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16703 Isodon lophanthoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12583 Sauromatum giganteum Species Araceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16354 Allium scorodoprasum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12583 Sauromatum giganteum Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16538 Stylophorum diphyllum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18319 Fraxinus japonica Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18135 Clausena vestita Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16771 Amomum mindanaense Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6896 Haliclona fulva Species Chalinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16703 Isodon lophanthoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17735 Acinetobacter genospecies Species Moraxellaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO19645 Chironia krebsii Species Gentianaceae 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 NPC228385 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 NPC308311
0.8333 Intermediate Similarity NPC8776
0.7755 Intermediate Similarity NPC477137
0.7692 Intermediate Similarity NPC600507
0.7 Intermediate Similarity NPC324602
0.6538 Remote Similarity NPC260323
0.6481 Remote Similarity NPC192948
0.6481 Remote Similarity NPC147179
0.6481 Remote Similarity NPC35797
0.6296 Remote Similarity NPC150601
0.6296 Remote Similarity NPC601694
0.625 Remote Similarity NPC36765
0.6226 Remote Similarity NPC27252
0.6226 Remote Similarity NPC472979
0.6182 Remote Similarity NPC11250
0.5893 Remote Similarity NPC219112
0.5763 Remote Similarity NPC58560
0.5614 Remote Similarity NPC172219
0.5614 Remote Similarity NPC304510
0.5593 Remote Similarity NPC471187
0.5536 Remote Similarity NPC604259
0.541 Remote Similarity NPC481087
0.5357 Remote Similarity NPC176279
0.5345 Remote Similarity NPC606176
0.5345 Remote Similarity NPC606869
0.5323 Remote Similarity NPC481011
0.5254 Remote Similarity NPC137750
0.5172 Remote Similarity NPC38893

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC228385 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