Natural Product: NPC284181

Natural Product IDNPC284181
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HGKRVDDOQIUQDS-RRCSTGOVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 57404492
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0000101] Eudesmane, isoeudesmane or cycloeudesmane sesquiterpenoids

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 HGKRVDDOQIUQDS-RRCSTGOVSA-N
Standard InCHI InChI=1S/C16H30O2/c1-14(2,17)12-7-10-15(3)8-6-9-16(4,18-5)13(15)11-12/h12-13,17H,6-11H2,1-5H3/t12-,13-,15-,16-/m1/s1
SMILES CC(C)([C@@H]1CC[C@@]2(C)CCC[C@](C)([C@@H]2C1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.22 Volume:   285.76
?
Van der Waals volume.
Dense:   0.89 LogP:   2.703
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.852
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.729
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   11.0
TPSA:   29.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.813 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.167 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:   0.056 Fluc inhibitor:   0.021
?
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:   0.922 Promiscuous compounds:   0.226

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.678 MDCK Permeability:   -4.83
Pgp-inhibitor:   0.416 Pgp-substrate:   0.022
PAMPA:   0.072
?
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):   0.003
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.163

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.968 MRP1:   0.376
Plasma Protein Binding (PPB):   77.473% Volume Distribution (VD):   -0.106
Fu: 18.192%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.699
BSEP inhibitor:   0.917

ADMET: Metabolism

CYP1A2-inhibitor:   0.463 CYP1A2-substrate:   0.558
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.026
CYP2C9-inhibitor:   0.692 CYP2C9-substrate:   0.01
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.466
CYP3A4-inhibitor:   0.136 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.662
HLM stability:   0.984
?
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):  11.11 Half-life (T1/2):  1.006

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.263
Human Hepatotoxicity (H-HT):  0.703 Drug-induced Liver Injury (DILI):  0.148
AMES Toxicity:  0.442 Rat Oral Acute Toxicity:  0.217
Maximum Recommended Daily Dose:  0.398 Skin Sensitization:  0.99
Carcinogencity:  0.932 Eye Corrosion:  0.757
Eye Irritation:  0.961 Respiratory Toxicity:  0.582
Drug-induced Neurotoxicity:  0.218 Ototoxicity:  0.355
Hematotoxicity:  0.354 Drug-induced Nephrotoxicity:  0.655
Genotoxicity:  0.136 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.042 Hek293 Cytotoxicity:  0.425
BCF:   1.831
?
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:   3.729
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.146
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.455
?
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
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota roots northern Saudi desert n.a. PMID[10924184]
NPO6831 Commiphora opobalsamum Species Burseraceae Eukaryota n.a. n.a. n.a. PMID[18177010]
NPO6831 Commiphora opobalsamum Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9036 Dipteryx lacunifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9883 Allium giganteum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7260 Angelica genuflexa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10085 Aspergillus varians Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3693 Calpurnia aurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29336 Corynandra chelidonii Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4463 Cytisus canariensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6022 Cytisus supinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24891 Elmerina caryae Species Aporpiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25831 Siphonoglossa sessilis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO5284 Ramalina hierrensis Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9639 Prunus puddum Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8810 Pinus austriaca Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2328 Lagochilus setulosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8297 Hydnellum caeruleum Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1586 Gorgonocephalus chilensis Species Gorgonocephalidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8985 Gazania rigens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5886 Fossombronia alaskana Species Fossombroniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO817 Dictamnus angustifolius Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7260 Angelica genuflexa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO817 Dictamnus angustifolius Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO817 Dictamnus angustifolius Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7260 Angelica genuflexa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8297 Hydnellum caeruleum Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10085 Aspergillus varians Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2328 Lagochilus setulosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7260 Angelica genuflexa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8985 Gazania rigens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24891 Elmerina caryae Species Aporpiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5284 Ramalina hierrensis Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1586 Gorgonocephalus chilensis Species Gorgonocephalidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8810 Pinus austriaca Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29336 Corynandra chelidonii Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO817 Dictamnus angustifolius Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9036 Dipteryx lacunifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6022 Cytisus supinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4463 Cytisus canariensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9639 Prunus puddum Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25831 Siphonoglossa sessilis n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO3693 Calpurnia aurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9883 Allium giganteum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11707 Ruta chalepensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6831 Commiphora opobalsamum Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5886 Fossombronia alaskana Species Fossombroniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8297 Hydnellum caeruleum Species Thelephoraceae 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 NPC284181 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC284181 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