Natural Product: NPC476046

Natural Product IDNPC476046
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1R,4Ar,7R,10As)-7-Ethenyl-1,4A,7-Trimethyl-3,4,6,8,8A,9,10,10A-Octahydro-2H-Phenanthrene-1-Carboxylic Acid
IUPAC Name (1R,4aR,7R,10aS)-7-ethenyl-1,4a,7-trimethyl-3,4,6,8,8a,9,10,10a-octahydro-2H-phenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL523295
PubChem CID 44566222
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 TVHDZSRRHQKNEZ-STWDSKMCSA-N
Standard InCHI InChI=1S/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,9,14,16H,1,6-8,10-13H2,2-4H3,(H,21,22)/t14?,16-,18+,19-,20+/m0/s1
SMILES C=C[C@]1(C)CC=C2C(C1)CC[C@H]1[C@@]2(C)CCC[C@@]1(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   338.478
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Van der Waals volume.
Dense:   0.893 LogP:   3.788
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.11
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.152
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   37.3
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.711 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.401 Fsp3:   0.75
MCE-18:   59.086
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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:   0.45 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
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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:   0.888 Promiscuous compounds:   0.028

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.698 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.352 Pgp-substrate:   0.003
PAMPA:   0.904
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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%):   0.09 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.379

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.06 MRP1:   0.984
Plasma Protein Binding (PPB):   96.855% Volume Distribution (VD):   -0.094
Fu: 2.741%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.904 BCRP inhibitor:   0.106
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.454 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.033 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.731 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.965 CYP3A4-substrate:   0.038
CYP2B6-substrate:   0.364 CYP2C8-inhibitor:   0.089
HLM stability:   0.096
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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):  2.549 Half-life (T1/2):  0.912

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.125
Human Hepatotoxicity (H-HT):  0.617 Drug-induced Liver Injury (DILI):  0.593
AMES Toxicity:  0.143 Rat Oral Acute Toxicity:  0.405
Maximum Recommended Daily Dose:  0.419 Skin Sensitization:  0.964
Carcinogencity:  0.813 Eye Corrosion:  0.521
Eye Irritation:  0.945 Respiratory Toxicity:  0.908
Drug-induced Neurotoxicity:  0.154 Ototoxicity:  0.411
Hematotoxicity:  0.271 Drug-induced Nephrotoxicity:  0.278
Genotoxicity:  0.24 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.106 Hek293 Cytotoxicity:  0.158
BCF:   1.453
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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:   4.082
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.383
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.943
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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
NPO33152 calceolaria pinifolia Species Calceolariaceae Eukaryota aerial part 46 km west of Puesto de Gendarmeria in the province of San Juan, Argentina (3021 S; 6940 W) 1997-Jan PMID[12608857]
NPO33152 calceolaria pinifolia Species Calceolariaceae 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
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 32.0 ug.mL-1 PMID[21377877]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 16.0 ug.mL-1 PMID[20695474]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 32.0 ug.mL-1 DrugMatrix in vitro pharmacology data
NPT19 Organism Escherichia coli Escherichia coli MIC > 128.0 ug.mL-1 PubChem BioAssay data set

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 NPC476046 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 NPC241854
1.0 High Similarity NPC251970
0.6415 Remote Similarity NPC610587
0.5283 Remote Similarity NPC601231
0.5283 Remote Similarity NPC607405
0.5094 Remote Similarity NPC222366
0.5094 Remote Similarity NPC286669
0.5094 Remote Similarity NPC476039
0.5094 Remote Similarity NPC602409

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476046 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