Natural Product: NPC31361

Natural Product IDNPC31361
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PTWUMSGLZPRHJW-RZRATATOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101627297
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 PTWUMSGLZPRHJW-RZRATATOSA-N
Standard InCHI InChI=1S/C20H26O4/c1-10-12-7-11-5-6-16-19(2,3)17(22)14(21)9-20(16,4)13(11)8-15(12)24-18(10)23/h7,13,15-17,22H,5-6,8-9H2,1-4H3/t13-,15-,16-,17-,20+/m1/s1
SMILES CC1=C2C=C3CC[C@@H]4C(C)(C)[C@@H](C(=O)C[C@@]4(C)[C@@H]3C[C@H]2OC1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.18 Volume:   344.865
?
Van der Waals volume.
Dense:   0.957 LogP:   1.404
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.846
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.501
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.694 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.822 Fsp3:   0.7
MCE-18:   69.882
?
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:   0.444 Fluc inhibitor:   0.01
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.094
?
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:   0.371 Promiscuous compounds:   0.364

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.831 MDCK Permeability:   -4.578
Pgp-inhibitor:   0.412 Pgp-substrate:   0.861
PAMPA:   0.986
?
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):   0.024
20% Bioavailability (F20%):   0.281 30% Bioavailability (F30%):   0.561
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.263 MRP1:   0.986
Plasma Protein Binding (PPB):   96.386% Volume Distribution (VD):   -0.121
Fu: 3.702%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.25
BSEP inhibitor:   0.957

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.71
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.865
CYP2C9-inhibitor:   0.832 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.036 CYP2D6-substrate:   0.03
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.873
HLM stability:   1.0
?
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):  6.783 Half-life (T1/2):  1.379

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.203
Human Hepatotoxicity (H-HT):  0.741 Drug-induced Liver Injury (DILI):  0.853
AMES Toxicity:  0.65 Rat Oral Acute Toxicity:  0.527
Maximum Recommended Daily Dose:  0.795 Skin Sensitization:  0.991
Carcinogencity:  0.895 Eye Corrosion:  0.084
Eye Irritation:  0.713 Respiratory Toxicity:  0.705
Drug-induced Neurotoxicity:  0.726 Ototoxicity:  0.476
Hematotoxicity:  0.726 Drug-induced Nephrotoxicity:  0.95
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.394 Hek293 Cytotoxicity:  0.171
BCF:   1.349
?
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:   3.917
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.447
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.911
?
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
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[10.1016/j.tet.2012.03.006]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. DOI[10.1016/j.tet.2012.03.006]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[16317898]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[17449162]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[19235686]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[19666019]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[22707864]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[23088673]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[2393954]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[25594733]
NPO21065 Euphorbia calyptrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[38528316]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[7912074]
NPO17794 Streptomyces violaceusniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[8557611]
NPO17794 Streptomyces violaceusniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28007 Cakile maritima Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28157 Vriesea regina Species Bromeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28299 Leucaena diversifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28142 Anthoceros agrestis Species Anthocerotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16779.1 Amaranthus hybridus subsp. cruentus Subspecies Amaranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1891 Chorilaena quercifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8081 Crataegus flava Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5402 Hypogymnia billardieri Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8081 Crataegus flava Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28157 Vriesea regina Species Bromeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28299 Leucaena diversifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27863 Diospyros nigra Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17794 Streptomyces violaceusniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21065 Euphorbia calyptrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1891 Chorilaena quercifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16779.1 Amaranthus hybridus subsp. cruentus Subspecies Amaranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28332 Lecidea tumida Species Lecideaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27972 Clitocybe phosphorea Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28007 Cakile maritima Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6223 Ceiba insignis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28142 Anthoceros agrestis Species Anthocerotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5402 Hypogymnia billardieri Species Parmeliaceae 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
NPT2854 Individual protein Voltage-gated potassium channel subunit Kv1.3 Homo sapiens Inhibition = 20.4 % PMID[37796721]
NPT2854 Individual protein Voltage-gated potassium channel subunit Kv1.3 Homo sapiens Inhibition n.a. n.a. % PMID[37796721]
NPT98 Individual protein HERG Homo sapiens Inhibition n.a. n.a. % PMID[37796721]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Activity n.a. n.a. n.a. PMID[36858948]
NPT71 Cell line HEK293 Homo sapiens Activity n.a. n.a. n.a. PMID[37796721]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 33820.0 nM PMID[36858948]

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 NPC31361 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
0.7321 Intermediate Similarity NPC611260
0.7143 Intermediate Similarity NPC221111
0.7143 Intermediate Similarity NPC280149
0.6842 Remote Similarity NPC606478
0.6102 Remote Similarity NPC34555
0.5968 Remote Similarity NPC482370
0.5902 Remote Similarity NPC479261
0.5806 Remote Similarity NPC296152
0.5714 Remote Similarity NPC479259
0.5538 Remote Similarity NPC482371
0.55 Remote Similarity NPC611362
0.541 Remote Similarity NPC479258
0.5217 Remote Similarity NPC482372
0.5082 Remote Similarity NPC609118

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC31361 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