Natural Product: NPC236588

Natural Product IDNPC236588
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 13,14,15,16-Tetranorlabdane-8Alpha,12,14-Triol
IUPAC Name (1R,2R,4aR,5R,8aS)-1-(2-hydroxyethyl)-5-(hydroxymethyl)-2,5,8a-trimethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-2-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL520723
PubChem CID 13854967
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001670] Tertiary alcohols

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 OSLJXGPVHCLGHU-XFIYOXNOSA-N
Standard InCHI InChI=1S/C16H30O3/c1-14(11-18)7-4-8-15(2)12(14)5-9-16(3,19)13(15)6-10-17/h12-13,17-19H,4-11H2,1-3H3/t12-,13+,14-,15-,16+/m0/s1
SMILES OCC[C@H]1[C@](C)(O)CC[C@@H]2[C@]1(C)CCC[C@@]2(C)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.22 Volume:   294.55
?
Van der Waals volume.
Dense:   0.917 LogP:   1.943
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.251
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.509
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   11.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.737 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.217 Fsp3:   1.0
MCE-18:   44.625
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.031 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
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:   0.925 Promiscuous compounds:   0.54

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.853 MDCK Permeability:   -4.682
Pgp-inhibitor:   0.002 Pgp-substrate:   0.261
PAMPA:   0.992
?
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):   0.131
20% Bioavailability (F20%):   0.28 30% Bioavailability (F30%):   0.256
50% Bioavailability (F50%):   0.951

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.127 MRP1:   0.467
Plasma Protein Binding (PPB):   47.853% Volume Distribution (VD):   -0.217
Fu: 54.547%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.683
OATP1B3 inhibitor:   0.677 BCRP inhibitor:   0.287
BSEP inhibitor:   0.181

ADMET: Metabolism

CYP1A2-inhibitor:   0.072 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.804 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.114 CYP2D6-substrate:   0.04
CYP3A4-inhibitor:   0.993 CYP3A4-substrate:   0.543
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.18
HLM stability:   0.168
?
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):  10.082 Half-life (T1/2):  1.338

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.194
Human Hepatotoxicity (H-HT):  0.729 Drug-induced Liver Injury (DILI):  0.028
AMES Toxicity:  0.312 Rat Oral Acute Toxicity:  0.116
Maximum Recommended Daily Dose:  0.197 Skin Sensitization:  0.995
Carcinogencity:  0.791 Eye Corrosion:  0.335
Eye Irritation:  0.989 Respiratory Toxicity:  0.33
Drug-induced Neurotoxicity:  0.044 Ototoxicity:  0.296
Hematotoxicity:  0.125 Drug-induced Nephrotoxicity:  0.6
Genotoxicity:  0.012 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.207 Hek293 Cytotoxicity:  0.298
BCF:   0.973
?
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:   3.272
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.824
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.898
?
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
NPO25356 Crassocephalum mannii Species Asteraceae Eukaryota aerial parts n.a. n.a. PMID[18473477]
NPO25356 Crassocephalum mannii Species Asteraceae Eukaryota n.a. aerial part n.a. PMID[18473477]
NPO25356 Crassocephalum mannii Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[18473477]
NPO25356 Crassocephalum mannii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25356 Crassocephalum mannii Species Asteraceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries Inhibition = 44.0 % PMID[18473477]
NPT31 Individual protein Cyclooxygenase-2 Homo sapiens Inhibition = 0.0 % PMID[18473477]

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 NPC236588 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
0.6047 Remote Similarity NPC476928
0.6 Remote Similarity NPC135438
0.5652 Remote Similarity NPC2524
0.5476 Remote Similarity NPC2648
0.5476 Remote Similarity NPC486120

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC236588 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