Natural Product: NPC289918

Natural Product IDNPC289918
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WLBPCNCJVFINNT-SESVXGAZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44605897
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 WLBPCNCJVFINNT-SESVXGAZSA-N
Standard InCHI InChI=1S/C23H27NO2/c1-20(2)18(25)10-11-21(3)22(4)14(9-12-23(20,21)26)13-16-15-7-5-6-8-17(15)24-19(16)22/h5-8,10-11,14,24,26H,9,12-13H2,1-4H3/t14-,21+,22+,23+/m0/s1
SMILES CC1(C)C(=O)C=C[C@]2(C)[C@]3(C)[C@@H](CC[C@@]12O)Cc1c2ccccc2[nH]c31

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   349.2 Volume:   376.34
?
Van der Waals volume.
Dense:   0.928 LogP:   3.275
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.189
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.057
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   53.09
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.745 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.337 Fsp3:   0.522
MCE-18:   114.086
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.347 Fluc inhibitor:   0.063
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.603
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.198
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.012 Promiscuous compounds:   0.422

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.042 MDCK Permeability:   -4.603
Pgp-inhibitor:   0.56 Pgp-substrate:   0.203
PAMPA:   0.837
?
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%):   0.233 30% Bioavailability (F30%):   0.183
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.988 MRP1:   0.699
Plasma Protein Binding (PPB):   92.116% Volume Distribution (VD):   0.315
Fu: 7.512%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.889 BCRP inhibitor:   0.968
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.989 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.14 CYP2C9-substrate:   0.856
CYP2D6-inhibitor:   0.426 CYP2D6-substrate:   0.673
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.993
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.754
HLM stability:   0.825
?
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):  13.363 Half-life (T1/2):  0.891

ADMET: Toxicity

hERG Blockers:  0.133 hERG Blockers (10um):  0.307
Human Hepatotoxicity (H-HT):  0.458 Drug-induced Liver Injury (DILI):  0.177
AMES Toxicity:  0.553 Rat Oral Acute Toxicity:  0.948
Maximum Recommended Daily Dose:  0.986 Skin Sensitization:  0.964
Carcinogencity:  0.864 Eye Corrosion:  0.011
Eye Irritation:  0.968 Respiratory Toxicity:  0.995
Drug-induced Neurotoxicity:  0.312 Ototoxicity:  0.513
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.821
Genotoxicity:  0.974 RPMI-8226 Immunitoxicity:  0.15
A549 Cytotoxicity:  0.066 Hek293 Cytotoxicity:  0.527
BCF:   0.953
?
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:   3.596
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.076
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.554
?
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
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. callus n.a. PMID[10552648]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. leaf n.a. PMID[18214349]
NPO33606 Verticillium lecanii 6144 Species n.a. Eukaryota n.a. Dominican Republic n.a. PMID[19863083]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. seed n.a. PMID[21049975]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21800857]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36840093]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38719900]
NPO8234 Vernonia galamensis Species Asteraceae Eukaryota n.a. seed n.a. PMID[9930408]
NPO4072 Anacyclus radiatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8771 Heterodermia dissecta Species Physciaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33606 Verticillium lecanii 6144 Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8009 Arctotis venusta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8620 Caesalpinia major Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8234 Vernonia galamensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5540 Amorpha canescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9455 Uncaria orientalis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9455 Uncaria orientalis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8620 Caesalpinia major Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8234 Vernonia galamensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4875 Ugni molinae Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4072 Anacyclus radiatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3668 Kalanchoe delagoensis Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9072 Bolocera tuediae Species Actiniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8009 Arctotis venusta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2389 Pinus japonica Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6292 Teucrium brevifolium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5832 Acacia nelsonii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4321 Siphula ceratites Species Icmadophilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8771 Heterodermia dissecta Species Physciaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7188 Zieria granulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9455 Uncaria orientalis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9330 Odinia antillensis Species Odiniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5540 Amorpha canescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24536 Senecio cylindricus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8620 Caesalpinia major Species Fabaceae 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 NPC289918 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
0.6857 Remote Similarity NPC99428
0.6111 Remote Similarity NPC302191
0.561 Remote Similarity NPC487205
0.5476 Remote Similarity NPC235900
0.5476 Remote Similarity NPC484479
0.5287 Remote Similarity NPC471284
0.5287 Remote Similarity NPC486860
0.525 Remote Similarity NPC198339
0.5227 Remote Similarity NPC487206
0.519 Remote Similarity NPC165201
0.519 Remote Similarity NPC602195
0.5176 Remote Similarity NPC224641
0.5122 Remote Similarity NPC487208
0.5116 Remote Similarity NPC487204
0.5116 Remote Similarity NPC123019
0.506 Remote Similarity NPC487209
0.506 Remote Similarity NPC609321

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC289918 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