Natural Product: NPC107258

Natural Product IDNPC107258
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Copalic Acid
IUPAC Name (E)-5-[(1R,4aR,8aR)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enoic acid
Synonyms Copalic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL102201
PubChem CID 11162521
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 JFQBNOIJWROZGE-HPMXROJMSA-N
Standard InCHI InChI=1S/C20H32O2/c1-14(13-18(21)22)7-9-16-15(2)8-10-17-19(3,4)11-6-12-20(16,17)5/h13,16-17H,2,6-12H2,1,3-5H3,(H,21,22)/b14-13+/t16-,17-,20+/m1/s1
SMILES C/C(=CC(=O)O)/CC[C@@H]1C(=C)CC[C@@H]2C(C)(C)CCC[C@@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.24 Volume:   347.034
?
Van der Waals volume.
Dense:   0.877 LogP:   4.617
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.333
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.143
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   14.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.542 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.899 Fsp3:   0.75
MCE-18:   42.743
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.132 Fluc inhibitor:   0.011
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.001
?
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:   0.946 Promiscuous compounds:   0.287

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.789 MDCK Permeability:   -4.779
Pgp-inhibitor:   0.736 Pgp-substrate:   0.0
PAMPA:   0.027
?
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%):   0.001 30% Bioavailability (F30%):   0.018
50% Bioavailability (F50%):   0.058

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.751
Plasma Protein Binding (PPB):   98.176% Volume Distribution (VD):   -0.54
Fu: 3.509%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.005
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.543 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.05
CYP2C9-inhibitor:   0.523 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.171 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.716 CYP3A4-substrate:   0.73
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.837
HLM stability:   0.554
?
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):  3.795 Half-life (T1/2):  0.772

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.04
Human Hepatotoxicity (H-HT):  0.798 Drug-induced Liver Injury (DILI):  0.72
AMES Toxicity:  0.113 Rat Oral Acute Toxicity:  0.118
Maximum Recommended Daily Dose:  0.321 Skin Sensitization:  0.787
Carcinogencity:  0.481 Eye Corrosion:  0.764
Eye Irritation:  0.984 Respiratory Toxicity:  0.79
Drug-induced Neurotoxicity:  0.167 Ototoxicity:  0.603
Hematotoxicity:  0.666 Drug-induced Nephrotoxicity:  0.842
Genotoxicity:  0.024 RPMI-8226 Immunitoxicity:  0.021
A549 Cytotoxicity:  0.01 Hek293 Cytotoxicity:  0.04
BCF:   2.012
?
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:   4.621
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.77
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.354
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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
NPO2430 Detarium microcarpum Species Fabaceae Eukaryota fruits n.a. n.a. PMID[16724838]
NPO32774 Copaifera Genus Fabaceae Eukaryota n.a. n.a. n.a. PMID[22440015]
NPO2430 Detarium microcarpum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2430 Detarium microcarpum Species Fabaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens Activity > 10.0 ug PMID[17067146]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2679 Cell line LLC-MK2 Macaca mulatta CC50 = 39400.0 nM PMID[19606850]
NPT985 Organism Cladosporium cucumerinum Cladosporium cucumerinum Activity > 100.0 ug PMID[21397998]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 42700.0 nM PMID[15921425]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi EC50 = 444000.0 nM PMID[11520227]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 1300.0 nM PMID[23805957]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 48.0 % PMID[15161186]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 30.0 % PubChem BioAssay data set
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 5.17 % PMID[24697496]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 0.71 % PMID[24697496]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 50.54 % PMID[12608850]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 43.58 % PMID[20521771]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 2.86 % PMID[20521771]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 0.1 % DOI[10.6019/CHEMBL1201861]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 72.57 % PMID[19721074]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 24.47 % PMID[19721074]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Change in body weight = 1.5 g DOI[10.1016/S0960-894X(01)80834-9]
NPT32 Organism Mus musculus Mus musculus Life span = 14.0 day DOI[10.1016/S0960-894X(01)80834-9]
NPT32 Organism Mus musculus Mus musculus ILS = 10.0 % DOI[10.1016/S0960-894X(01)80834-9]





 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 NPC107258 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
0.7609 Intermediate Similarity NPC194322
0.7609 Intermediate Similarity NPC488496
0.7609 Intermediate Similarity NPC488504
0.6731 Remote Similarity NPC488497
0.6667 Remote Similarity NPC259156
0.6531 Remote Similarity NPC133253
0.64 Remote Similarity NPC159148
0.64 Remote Similarity NPC281880
0.6383 Remote Similarity NPC119734
0.62 Remote Similarity NPC488498
0.62 Remote Similarity NPC61952
0.62 Remote Similarity NPC603184
0.6038 Remote Similarity NPC170303
0.5962 Remote Similarity NPC472813
0.5741 Remote Similarity NPC75485
0.5741 Remote Similarity NPC168975
0.5577 Remote Similarity NPC132542
0.551 Remote Similarity NPC226997
0.549 Remote Similarity NPC185587
0.5472 Remote Similarity NPC180015
0.54 Remote Similarity NPC68703
0.5385 Remote Similarity NPC35655
0.5345 Remote Similarity NPC478391
0.5345 Remote Similarity NPC485191
0.5306 Remote Similarity NPC41160
0.5306 Remote Similarity NPC67840
0.5273 Remote Similarity NPC488500
0.5238 Remote Similarity NPC103290
0.5192 Remote Similarity NPC169275
0.5192 Remote Similarity NPC52449
0.5091 Remote Similarity NPC251528

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC107258 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