Natural Product: NPC477782

Natural Product IDNPC477782
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 16-Hydroxy-8(17),13-labdadien-15,16-olid-19-oic acid
IUPAC Name (1S,4aR,5S,8aR)-5-[2-(2-hydroxy-5-oxo-2H-furan-3-yl)ethyl]-1,4a-dimethyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14287153
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 GZTUAPFQPZVTGA-LTWMUGOISA-N
Standard InCHI InChI=1S/C20H28O5/c1-12-5-8-15-19(2,9-4-10-20(15,3)18(23)24)14(12)7-6-13-11-16(21)25-17(13)22/h11,14-15,17,22H,1,4-10H2,2-3H3,(H,23,24)/t14-,15+,17?,19+,20-/m0/s1
SMILES C[C@]12CCC[C@]([C@@H]1CCC(=C)[C@@H]2CCC3=CC(=O)OC3O)(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.19 Volume:   362.212
?
Van der Waals volume.
Dense:   0.961 LogP:   2.181
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.103
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.825
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.601 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.507 Fsp3:   0.7
MCE-18:   56.941
?
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:   0.294 Fluc inhibitor:   0.037
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.005
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.368 Promiscuous compounds:   0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.872 MDCK Permeability:   -4.83
Pgp-inhibitor:   0.04 Pgp-substrate:   0.0
PAMPA:   0.925
?
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):   0.007
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.048
50% Bioavailability (F50%):   0.151

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.942
Plasma Protein Binding (PPB):   94.985% Volume Distribution (VD):   -0.53
Fu: 3.125%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.0
BSEP inhibitor:   0.972

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.846 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.413 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.003
HLM stability:   0.006
?
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):  2.524 Half-life (T1/2):  1.311

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.181
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.486
AMES Toxicity:  0.273 Rat Oral Acute Toxicity:  0.58
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.986
Carcinogencity:  0.864 Eye Corrosion:  0.023
Eye Irritation:  0.742 Respiratory Toxicity:  0.682
Drug-induced Neurotoxicity:  0.352 Ototoxicity:  0.622
Hematotoxicity:  0.15 Drug-induced Nephrotoxicity:  0.886
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.019 Hek293 Cytotoxicity:  0.138
BCF:   0.88
?
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:   3.884
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.615
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.761
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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
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota Leaves and branches Soorkesh Valley, Gollestan, Iran n.a. PMID[15104493]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota leaves Soorkesh Valley, Gollestan, Iran n.a. PMID[15104493]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28256 Platycladus orientalis Species Cupressaceae 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 84100 nM PMID[15104493]

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 NPC477782 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
0.7458 Intermediate Similarity NPC477783
0.7368 Intermediate Similarity NPC40228
0.6909 Remote Similarity NPC481630
0.6724 Remote Similarity NPC239098
0.6667 Remote Similarity NPC600691
0.6552 Remote Similarity NPC18819
0.6552 Remote Similarity NPC46610
0.6452 Remote Similarity NPC14203
0.6452 Remote Similarity NPC229584
0.6393 Remote Similarity NPC232344
0.6379 Remote Similarity NPC59436
0.6316 Remote Similarity NPC488498
0.6316 Remote Similarity NPC61952
0.6316 Remote Similarity NPC603184
0.6271 Remote Similarity NPC91369
0.6207 Remote Similarity NPC237591
0.6207 Remote Similarity NPC72343
0.6207 Remote Similarity NPC3753
0.6167 Remote Similarity NPC269543
0.6167 Remote Similarity NPC247783
0.6 Remote Similarity NPC471159
0.6 Remote Similarity NPC123880
0.5932 Remote Similarity NPC198240
0.5932 Remote Similarity NPC36616
0.5763 Remote Similarity NPC99154
0.5397 Remote Similarity NPC472811
0.5211 Remote Similarity NPC610335
0.5161 Remote Similarity NPC161923
0.5161 Remote Similarity NPC183503
0.5161 Remote Similarity NPC283908
0.5161 Remote Similarity NPC103958
0.5161 Remote Similarity NPC610917
0.5079 Remote Similarity NPC165711
0.5079 Remote Similarity NPC109854

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477782 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