Natural Product: NPC91678

Natural Product IDNPC91678
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FRROOMGFBCWJRP-LBPRGKRZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 24823534
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002955] Tetrahydroisoquinolines

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 FRROOMGFBCWJRP-LBPRGKRZSA-N
Standard InCHI InChI=1S/C15H24N4O2/c1-20-13-8-10-5-7-18-12(4-3-6-19-15(16)17)11(10)9-14(13)21-2/h8-9,12,18H,3-7H2,1-2H3,(H4,16,17,19)/t12-/m0/s1
SMILES COc1cc2CCN[C@@H](CCCNC(=N)N)c2cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   292.19 Volume:   301.905
?
Van der Waals volume.
Dense:   0.968 LogP:   0.271
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.455
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.539
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   12.0
TPSA:   92.39
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.359 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.931 Fsp3:   0.533
MCE-18:   39.13
?
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:   0.165 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.079
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.62
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.177

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.846 MDCK Permeability:   -5.116
Pgp-inhibitor:   0.0 Pgp-substrate:   1.0
PAMPA:   0.642
?
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):   0.341
20% Bioavailability (F20%):   0.166 30% Bioavailability (F30%):   0.413
50% Bioavailability (F50%):   0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.504
Plasma Protein Binding (PPB):   30.54% Volume Distribution (VD):   0.221
Fu: 61.175%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.374
OATP1B3 inhibitor:   0.885 BCRP inhibitor:   0.005
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.984 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.631
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.668 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.007
?
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):  7.492 Half-life (T1/2):  1.713

ADMET: Toxicity

hERG Blockers:  0.727 hERG Blockers (10um):  0.743
Human Hepatotoxicity (H-HT):  0.512 Drug-induced Liver Injury (DILI):  0.121
AMES Toxicity:  0.412 Rat Oral Acute Toxicity:  0.599
Maximum Recommended Daily Dose:  0.289 Skin Sensitization:  0.997
Carcinogencity:  0.412 Eye Corrosion:  0.0
Eye Irritation:  0.03 Respiratory Toxicity:  0.992
Drug-induced Neurotoxicity:  0.409 Ototoxicity:  0.487
Hematotoxicity:  0.09 Drug-induced Nephrotoxicity:  0.819
Genotoxicity:  0.823 RPMI-8226 Immunitoxicity:  0.015
A549 Cytotoxicity:  0.009 Hek293 Cytotoxicity:  0.141
BCF:   0.469
?
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:   3.176
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.595
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.804
?
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
NPO874 Narthecium asiaticum Species Nartheciaceae Eukaryota n.a. n.a. n.a. PMID[14980692]
NPO244 Stachyurus himalaicus Species Stachyuraceae Eukaryota n.a. n.a. n.a. PMID[17851408]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. bark n.a. PMID[20167482]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. n.a. PMID[21608987]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. stem n.a. PMID[27113553]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. root n.a. PMID[2801129]
NPO23104 Wedelia scaberrima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2277 Angylocalyx braunii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4000 Archidendron lucidum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7235 Brachychiton populneum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2213 Chavica betle n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO5599 Chrysocoma peduncularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4786 Chrysotila lamellosa Species Isochrysidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7379 Clostridium butyricum Species Clostridiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1384 Cucumis myriocarpus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO962 Vernonanthura pinguis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO874 Narthecium asiaticum Species Nartheciaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7897 Passiflora foetida Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7026 Vismia orientalis Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO591 Penicillium meleagrinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5154 Tsuga diversifolia Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7098 Phebalium ambiens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1249 Euphorbia sieboldiana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4129 Veronica persica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO244 Stachyurus himalaicus Species Stachyuraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota Fruit Juice n.a. n.a. Database[FooDB]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. Database[FooDB]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. Database[FooDB]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4129 Veronica persica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7026 Vismia orientalis Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1384 Cucumis myriocarpus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO7026 Vismia orientalis Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1384 Cucumis myriocarpus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4129 Veronica persica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO244 Stachyurus himalaicus Species Stachyuraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO874 Narthecium asiaticum Species Nartheciaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5599 Chrysocoma peduncularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO591 Penicillium meleagrinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO244 Stachyurus himalaicus Species Stachyuraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2348 Tripterygium regelii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO962 Vernonanthura pinguis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4000 Archidendron lucidum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4786 Chrysotila lamellosa Species Isochrysidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4129 Veronica persica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10856 Passiflora edulis Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7098 Phebalium ambiens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2213 Chavica betle n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO7026 Vismia orientalis Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1249 Euphorbia sieboldiana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7379 Clostridium butyricum Species Clostridiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO2277 Angylocalyx braunii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7235 Brachychiton populneum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5154 Tsuga diversifolia Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7897 Passiflora foetida Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23104 Wedelia scaberrima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1384 Cucumis myriocarpus Species Cucurbitaceae 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 NPC91678 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
0.5192 Remote Similarity NPC253429

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC91678 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