Natural Product: NPC147784

Natural Product IDNPC147784
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WYJKGKPQXWDIQP-BRUWWATDSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11141639
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 WYJKGKPQXWDIQP-BRUWWATDSA-N
Standard InCHI InChI=1S/C21H32O2/c1-7-15(2)9-11-17-16(3)10-12-18-20(17,4)13-8-14-21(18,5)19(22)23-6/h7,9,17-18H,1,3,8,10-14H2,2,4-6H3/b15-9+/t17-,18+,20+,21-/m0/s1
SMILES C=C/C(=C/C[C@H]1C(=C)CC[C@@H]2[C@]1(C)CCC[C@]2(C)C(=O)OC)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.24 Volume:   361.694
?
Van der Waals volume.
Dense:   0.874 LogP:   4.741
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.934
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.157
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.391 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.276 Fsp3:   0.667
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:   0.274 Fluc inhibitor:   0.007
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.976 Promiscuous compounds:   0.085

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.606 MDCK Permeability:   -4.806
Pgp-inhibitor:   0.971 Pgp-substrate:   0.0
PAMPA:   0.004
?
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%):   0.335 30% Bioavailability (F30%):   0.405
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.993
Plasma Protein Binding (PPB):   98.033% Volume Distribution (VD):   0.089
Fu: 1.953%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.306
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.34 CYP1A2-substrate:   0.981
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.027
CYP2C9-inhibitor:   0.347 CYP2C9-substrate:   0.128
CYP2D6-inhibitor:   0.972 CYP2D6-substrate:   0.905
CYP3A4-inhibitor:   0.921 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  8.636 Half-life (T1/2):  0.299

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.538
Human Hepatotoxicity (H-HT):  0.615 Drug-induced Liver Injury (DILI):  0.432
AMES Toxicity:  0.287 Rat Oral Acute Toxicity:  0.62
Maximum Recommended Daily Dose:  0.713 Skin Sensitization:  0.831
Carcinogencity:  0.585 Eye Corrosion:  0.283
Eye Irritation:  0.883 Respiratory Toxicity:  0.872
Drug-induced Neurotoxicity:  0.67 Ototoxicity:  0.336
Hematotoxicity:  0.281 Drug-induced Nephrotoxicity:  0.376
Genotoxicity:  0.648 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.218 Hek293 Cytotoxicity:  0.363
BCF:   2.178
?
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:   4.651
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.906
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.444
?
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
NPO21902 Thalictrum sachalinense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23029 Tetradenia riparia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21769 Pterocarpus dalbergioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23197 Juniperus oxycedrus Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22349 Cucumaria frondosa Species Cucumariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19830 Chamonixia caespitosa Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20157 Boykinia tellimoides Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13434 Acremonium furcatum Species Plectosphaerellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23197 Juniperus oxycedrus Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23197 Juniperus oxycedrus Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19830 Chamonixia caespitosa Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23029 Tetradenia riparia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21769 Pterocarpus dalbergioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13434 Acremonium furcatum Species Plectosphaerellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23197 Juniperus oxycedrus Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20157 Boykinia tellimoides Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22349 Cucumaria frondosa Species Cucumariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21902 Thalictrum sachalinense Species Ranunculaceae 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

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 NPC147784 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
0.6667 Remote Similarity NPC268039
0.6415 Remote Similarity NPC200513
0.6226 Remote Similarity NPC144947
0.6122 Remote Similarity NPC149680
0.6122 Remote Similarity NPC600344
0.5849 Remote Similarity NPC166797
0.5556 Remote Similarity NPC478390
0.5455 Remote Similarity NPC139566
0.5455 Remote Similarity NPC899
0.5357 Remote Similarity NPC12170
0.5345 Remote Similarity NPC469
0.5345 Remote Similarity NPC478393
0.5323 Remote Similarity NPC16922
0.5263 Remote Similarity NPC217394
0.5263 Remote Similarity NPC238146
0.5185 Remote Similarity NPC169275
0.5185 Remote Similarity NPC52449
0.5185 Remote Similarity NPC185587
0.5172 Remote Similarity NPC79027
0.5091 Remote Similarity NPC175334

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC147784 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
0.6415 Remote Similarity NPD4752 Clinical (unspecified phase)

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