Natural Product: NPC142326

Natural Product IDNPC142326
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (15R)-16-Hydroxyabieta-8,11,13-Trien-19-Oic Acid
IUPAC Name (1S,4aS,10aR)-7-[(2R)-1-hydroxypropan-2-yl]-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2431469
PubChem CID 72705063
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 GOADHRDZJUNBQS-KORVSZGISA-N
Standard InCHI InChI=1S/C20H28O3/c1-13(12-21)14-5-7-16-15(11-14)6-8-17-19(16,2)9-4-10-20(17,3)18(22)23/h5,7,11,13,17,21H,4,6,8-10,12H2,1-3H3,(H,22,23)/t13-,17+,19+,20-/m0/s1
SMILES OC[C@@H](c1ccc2c(c1)CC[C@@H]1[C@]2(C)CCC[C@]1(C)C(=O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   344.632
?
Van der Waals volume.
Dense:   0.918 LogP:   3.253
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.841
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.73
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.89 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.748 Fsp3:   0.65
MCE-18:   73.182
?
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:   0.05 Fluc inhibitor:   0.017
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.046
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.021
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.178 Promiscuous compounds:   0.033

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.767 MDCK Permeability:   -5.103
Pgp-inhibitor:   0.009 Pgp-substrate:   0.033
PAMPA:   0.991
?
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%):   0.011 30% Bioavailability (F30%):   0.026
50% Bioavailability (F50%):   0.202

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.972
Plasma Protein Binding (PPB):   95.087% Volume Distribution (VD):   -0.173
Fu: 3.722%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   0.801 BCRP inhibitor:   0.01
BSEP inhibitor:   0.822

ADMET: Metabolism

CYP1A2-inhibitor:   0.152 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.793 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.938 CYP3A4-substrate:   0.119
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.125
HLM stability:   0.016
?
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):  2.701 Half-life (T1/2):  1.073

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.057
Human Hepatotoxicity (H-HT):  0.759 Drug-induced Liver Injury (DILI):  0.37
AMES Toxicity:  0.216 Rat Oral Acute Toxicity:  0.097
Maximum Recommended Daily Dose:  0.329 Skin Sensitization:  0.964
Carcinogencity:  0.823 Eye Corrosion:  0.041
Eye Irritation:  0.933 Respiratory Toxicity:  0.398
Drug-induced Neurotoxicity:  0.011 Ototoxicity:  0.825
Hematotoxicity:  0.588 Drug-induced Nephrotoxicity:  0.912
Genotoxicity:  0.228 RPMI-8226 Immunitoxicity:  0.025
A549 Cytotoxicity:  0.079 Hek293 Cytotoxicity:  0.127
BCF:   1.056
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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:   3.906
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.456
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.754
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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
NPO14738 Illicium majus Species Schisandraceae Eukaryota Roots n.a. n.a. PMID[24070022]
NPO14738 Illicium majus Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14738 Illicium majus Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14738 Illicium majus Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT189 Cell line Vero Chlorocebus aethiops TC50 = 66.7 uM/ml PMID[26546212]
NPT3119 Organism Human coxsackievirus B3 Human coxsackievirus B3 IC50 = 12800000.0 nM DrugMatrix in vivo data: Pathology

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 NPC142326 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 NPC94751
0.8269 Intermediate Similarity NPC128248
0.8269 Intermediate Similarity NPC136810
0.7368 Intermediate Similarity NPC212891
0.7368 Intermediate Similarity NPC480861
0.7321 Intermediate Similarity NPC95126
0.6842 Remote Similarity NPC133809
0.65 Remote Similarity NPC221275
0.6441 Remote Similarity NPC162935
0.6441 Remote Similarity NPC249340
0.6379 Remote Similarity NPC42657
0.629 Remote Similarity NPC45794
0.6129 Remote Similarity NPC480862
0.6129 Remote Similarity NPC480860
0.6 Remote Similarity NPC480867
0.5968 Remote Similarity NPC603947
0.5968 Remote Similarity NPC608624
0.5806 Remote Similarity NPC234337
0.5806 Remote Similarity NPC133389
0.5397 Remote Similarity NPC93287
0.5362 Remote Similarity NPC480863
0.5238 Remote Similarity NPC225079
0.5238 Remote Similarity NPC471186
0.5077 Remote Similarity NPC471189
0.5072 Remote Similarity NPC480866

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC142326 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
0.6066 Remote Similarity NPD4199 Phase 3

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