Natural Product: NPC168070

Natural Product IDNPC168070
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NEMKMHUCTPZMSO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5317555
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000089] Pyridines and derivatives

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 NEMKMHUCTPZMSO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H11NO/c1-2-8-7-10-5-3-9(8)4-6-11/h2-3,5,7,11H,1,4,6H2
SMILES C=Cc1cnccc1CCO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   149.08 Volume:   164.905
?
Van der Waals volume.
Dense:   0.904 LogP:   0.636
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.643
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.06
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   7.0
TPSA:   33.12
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.701 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.67 Fsp3:   0.222
MCE-18:   5.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.008 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.018
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.525 Promiscuous compounds:   0.514

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.737 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.091 Pgp-substrate:   0.433
PAMPA:   0.707
?
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):   0.052
20% Bioavailability (F20%):   0.258 30% Bioavailability (F30%):   0.291
50% Bioavailability (F50%):   0.715

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.155 MRP1:   0.548
Plasma Protein Binding (PPB):   61.105% Volume Distribution (VD):   0.394
Fu: 37.958%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.536
OATP1B3 inhibitor:   0.74 BCRP inhibitor:   0.771
BSEP inhibitor:   0.48

ADMET: Metabolism

CYP1A2-inhibitor:   0.062 CYP1A2-substrate:   0.111
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.251
CYP2C9-inhibitor:   0.509 CYP2C9-substrate:   0.443
CYP2D6-inhibitor:   0.265 CYP2D6-substrate:   0.955
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.884
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.998
HLM stability:   0.297
?
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):  8.447 Half-life (T1/2):  1.582

ADMET: Toxicity

hERG Blockers:  0.086 hERG Blockers (10um):  0.393
Human Hepatotoxicity (H-HT):  0.36 Drug-induced Liver Injury (DILI):  0.174
AMES Toxicity:  0.416 Rat Oral Acute Toxicity:  0.24
Maximum Recommended Daily Dose:  0.122 Skin Sensitization:  0.952
Carcinogencity:  0.623 Eye Corrosion:  0.891
Eye Irritation:  0.994 Respiratory Toxicity:  0.619
Drug-induced Neurotoxicity:  0.404 Ototoxicity:  0.334
Hematotoxicity:  0.185 Drug-induced Nephrotoxicity:  0.155
Genotoxicity:  0.049 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.101
BCF:   0.203
?
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:   2.211
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.734
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.895
?
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
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1002/elan.200403102]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2012.02.124]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)94333-4]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/j.1399-3054.2000.1100409.x]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[11077184]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[17328234]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[18321056]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[18406151]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. xylem n.a. PMID[21348469]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower n.a. PMID[21804227]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower bud n.a. PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota flower buds Henan province, China 2005-MAY PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. leaf n.a. PMID[23265495]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[24279769]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. PMID[3735324]
NPO4304 Gentiana tibetica Species Gentianaceae Eukaryota n.a. root n.a. PMID[9611826]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4304 Gentiana tibetica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16412 Menyanthes trifoliata Species Menyanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16412 Menyanthes trifoliata Species Menyanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4304 Gentiana tibetica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4304 Gentiana tibetica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16412 Menyanthes trifoliata Species Menyanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16412 Menyanthes trifoliata Species Menyanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4304 Gentiana tibetica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2806 Gentiana nivalis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16412 Menyanthes trifoliata Species Menyanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12582 Camptotheca acuminata Species Nyssaceae 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 NPC168070 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 NPC168070 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