Natural Product: NPC140233

Natural Product IDNPC140233
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QYPBSHVQNJCZQA-SJCKPFSWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689082
PubChem CID 51040057
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0001760] Dolabellane and neodolabellane 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 QYPBSHVQNJCZQA-SJCKPFSWSA-N
Standard InCHI InChI=1S/C20H32O/c1-14(2)16-9-12-19(4)11-8-15(3)6-7-18-20(5,21-18)13-10-17(16)19/h8,16-18H,1,6-7,9-13H2,2-5H3/b15-8+/t16-,17+,18+,19+,20+/m1/s1
SMILES C/C/1=CC[C@@]2(C)CC[C@@H]([C@@H]2CC[C@]2([C@H](CC1)O2)C)C(=C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.25 Volume:   332.324
?
Van der Waals volume.
Dense:   0.867 LogP:   4.73
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.671
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.858
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   12.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.448 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.833 Fsp3:   0.8
MCE-18:   53.333
?
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:   0.46 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
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:   0.973 Promiscuous compounds:   0.537

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.547 MDCK Permeability:   -4.706
Pgp-inhibitor:   0.922 Pgp-substrate:   0.001
PAMPA:   0.012
?
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):   0.001
20% Bioavailability (F20%):   0.166 30% Bioavailability (F30%):   0.307
50% Bioavailability (F50%):   0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.915 MRP1:   0.683
Plasma Protein Binding (PPB):   92.221% Volume Distribution (VD):   0.587
Fu: 8.458%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.931
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.495 CYP1A2-substrate:   0.657
CYP2C19-inhibitor:   0.981 CYP2C19-substrate:   0.097
CYP2C9-inhibitor:   0.294 CYP2C9-substrate:   0.095
CYP2D6-inhibitor:   0.975 CYP2D6-substrate:   0.344
CYP3A4-inhibitor:   0.442 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.075 CYP2C8-inhibitor:   0.969
HLM stability:   0.721
?
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):  14.467 Half-life (T1/2):  0.994

ADMET: Toxicity

hERG Blockers:  0.175 hERG Blockers (10um):  0.343
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.336
AMES Toxicity:  0.216 Rat Oral Acute Toxicity:  0.226
Maximum Recommended Daily Dose:  0.506 Skin Sensitization:  0.896
Carcinogencity:  0.768 Eye Corrosion:  0.532
Eye Irritation:  0.989 Respiratory Toxicity:  0.648
Drug-induced Neurotoxicity:  0.382 Ototoxicity:  0.263
Hematotoxicity:  0.32 Drug-induced Nephrotoxicity:  0.242
Genotoxicity:  0.028 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.107 Hek293 Cytotoxicity:  0.459
BCF:   3.466
?
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:   4.95
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.541
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.926
?
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
NPO31140 Dilophus spiralis Species Dictyotaceae Eukaryota n.a. at a depth of 0.1-1 m, Elafonissos Island (3630' N, 2258' E), south of Peloponnese, Greece 2004-APR PMID[21190330]
NPO31140 Dilophus spiralis Species Dictyotaceae Eukaryota n.a. n.a. n.a. PMID[21190330]
NPO31140 Dilophus spiralis Species Dictyotaceae Eukaryota n.a. Elafonissos Island (GPS coordinates 3630' N, 2258' E), south of Peloponnese, Greece 2004-APR PMID[21190330]
NPO31140 Dilophus spiralis Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29308 Mycobacterium marinum Species Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29313 Halomonas meridiana Species Halomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29308 Mycobacterium marinum Species Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29313 Halomonas meridiana Species Halomonadaceae Bacteria 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
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 128.0 ug.mL-1 PMID[21190330]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 128.0 ug.mL-1 PMID[21190330]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 4.0 ug.mL-1 PMID[21190330]

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 NPC140233 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
0.6415 Remote Similarity NPC92909
0.6415 Remote Similarity NPC107783
0.6275 Remote Similarity NPC287744
0.5849 Remote Similarity NPC469691
0.5849 Remote Similarity NPC167049
0.5625 Remote Similarity NPC13789
0.5625 Remote Similarity NPC7491
0.5625 Remote Similarity NPC65786
0.5625 Remote Similarity NPC101285
0.5625 Remote Similarity NPC607448
0.5517 Remote Similarity NPC329763
0.5417 Remote Similarity NPC49088
0.5385 Remote Similarity NPC56419
0.5273 Remote Similarity NPC475771

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC140233 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