Natural Product: NPC130459

Natural Product IDNPC130459
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FLGAFUAMEXILLB-KDGRZGFDSA-N
IUPAC Name n.a.
Synonyms Trachyloban-19-Oic Acid; Trachyloban-19-Oicacid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL511801
PubChem CID 44560009
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003782] Kaurane 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 FLGAFUAMEXILLB-KDGRZGFDSA-N
Standard InCHI InChI=1S/C20H30O2/c1-17-6-4-7-18(2,16(21)22)14(17)5-8-20-10-13-12(9-15(17)20)19(13,3)11-20/h12-15H,4-11H2,1-3H3,(H,21,22)/t12-,13+,14-,15-,17+,18-,19+,20-/m0/s1
SMILES OC(=O)[C@@]1(C)CCC[C@@]2([C@@H]1CC[C@]13[C@H]2C[C@H]2[C@@H](C1)[C@@]2(C3)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   326.638
?
Van der Waals volume.
Dense:   0.925 LogP:   3.412
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.939
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.904
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   21.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.76 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.052 Fsp3:   0.95
MCE-18:   122.256
?
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:   0.43 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.652 Promiscuous compounds:   0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.168 MDCK Permeability:   -5.041
Pgp-inhibitor:   0.023 Pgp-substrate:   0.009
PAMPA:   0.921
?
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):   0.009
20% Bioavailability (F20%):   0.111 30% Bioavailability (F30%):   0.041
50% Bioavailability (F50%):   0.169

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.143 MRP1:   0.877
Plasma Protein Binding (PPB):   90.432% Volume Distribution (VD):   -0.367
Fu: 9.91%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.912 BCRP inhibitor:   0.084
BSEP inhibitor:   0.862

ADMET: Metabolism

CYP1A2-inhibitor:   0.037 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.919 CYP3A4-substrate:   0.048
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
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):  3.752 Half-life (T1/2):  1.231

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.085
Human Hepatotoxicity (H-HT):  0.704 Drug-induced Liver Injury (DILI):  0.299
AMES Toxicity:  0.259 Rat Oral Acute Toxicity:  0.285
Maximum Recommended Daily Dose:  0.344 Skin Sensitization:  0.982
Carcinogencity:  0.888 Eye Corrosion:  0.598
Eye Irritation:  0.942 Respiratory Toxicity:  0.927
Drug-induced Neurotoxicity:  0.05 Ototoxicity:  0.534
Hematotoxicity:  0.571 Drug-induced Nephrotoxicity:  0.849
Genotoxicity:  0.069 RPMI-8226 Immunitoxicity:  0.015
A549 Cytotoxicity:  0.043 Hek293 Cytotoxicity:  0.065
BCF:   2.052
?
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:   4.648
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.741
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.303
?
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
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. small food enterprises (Zvijezda d.d., Zagreb, Croatia) n.a. DOI[10.1002/EJLT.200900231]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11746-997-0093-1]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[16660462]
NPO454 Helianthus annuus Species Asteraceae Eukaryota flower petals n.a. n.a. PMID[17480100]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Flowers n.a. n.a. PMID[6361218]
NPO27199 Croton macrostachys Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Pollen Or Spore n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Flower Essent. Oil n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27199 Croton macrostachys Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO454 Helianthus annuus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27199 Croton macrostachys Species Euphorbiaceae 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
NPT602 Organism Mycobacterium smegmatis Mycobacterium smegmatis MIC = 6.25 ug.mL-1 PMID[6361218]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 128.0 ug.mL-1 PMID[11473422]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 6.25 ug.mL-1 PMID[6361218]

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 NPC130459 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 NPC474221
0.6038 Remote Similarity NPC486658
0.58 Remote Similarity NPC330659
0.58 Remote Similarity NPC244708
0.58 Remote Similarity NPC161187
0.5686 Remote Similarity NPC201027
0.5686 Remote Similarity NPC268736
0.5686 Remote Similarity NPC252032
0.5686 Remote Similarity NPC319671
0.5686 Remote Similarity NPC477931
0.5686 Remote Similarity NPC476734
0.5439 Remote Similarity NPC483370
0.537 Remote Similarity NPC180199
0.537 Remote Similarity NPC477919
0.5283 Remote Similarity NPC248758
0.5283 Remote Similarity NPC170985
0.5273 Remote Similarity NPC607026
0.5185 Remote Similarity NPC212661
0.5185 Remote Similarity NPC471035
0.5098 Remote Similarity NPC478660
0.5098 Remote Similarity NPC601231
0.5098 Remote Similarity NPC607405
0.5091 Remote Similarity NPC600598

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC130459 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
0.5882 Remote Similarity NPD4224 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