Natural Product: NPC159150

Natural Product IDNPC159150
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sarmentosine
IUPAC Name (2E,6E)-7-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylhepta-2,6-dien-1-one
Synonyms Sarmentosine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2205105
PubChem CID 10935441
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 RUXALYXWBMBHLF-FCXRPNKRSA-N
Standard InCHI InChI=1S/C18H21NO3/c20-18(19-11-5-6-12-19)8-4-2-1-3-7-15-9-10-16-17(13-15)22-14-21-16/h3-4,7-10,13H,1-2,5-6,11-12,14H2/b7-3+,8-4+
SMILES O=C(N1CCCC1)/C=C/CC/C=C/c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.15 Volume:   315.764
?
Van der Waals volume.
Dense:   0.947 LogP:   3.489
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.07
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.232
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   38.77
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.618 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.459 Fsp3:   0.389
MCE-18:   33.6
?
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:   0.459 Fluc inhibitor:   0.996
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.433
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.747
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.018 Promiscuous compounds:   0.068

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.757 MDCK Permeability:   -4.733
Pgp-inhibitor:   0.976 Pgp-substrate:   0.0
PAMPA:   0.009
?
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):   0.004
20% Bioavailability (F20%):   0.281 30% Bioavailability (F30%):   0.03
50% Bioavailability (F50%):   0.377

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.226 MRP1:   0.011
Plasma Protein Binding (PPB):   98.211% Volume Distribution (VD):   0.055
Fu: 1.603%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.85
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.041
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.64 CYP1A2-substrate:   0.853
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.986
CYP2C9-inhibitor:   0.377 CYP2C9-substrate:   0.933
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.864
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.503
?
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):  5.514 Half-life (T1/2):  0.615

ADMET: Toxicity

hERG Blockers:  0.628 hERG Blockers (10um):  0.588
Human Hepatotoxicity (H-HT):  0.75 Drug-induced Liver Injury (DILI):  0.583
AMES Toxicity:  0.679 Rat Oral Acute Toxicity:  0.145
Maximum Recommended Daily Dose:  0.846 Skin Sensitization:  0.883
Carcinogencity:  0.369 Eye Corrosion:  0.003
Eye Irritation:  0.368 Respiratory Toxicity:  0.612
Drug-induced Neurotoxicity:  0.626 Ototoxicity:  0.317
Hematotoxicity:  0.334 Drug-induced Nephrotoxicity:  0.599
Genotoxicity:  0.661 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.188 Hek293 Cytotoxicity:  0.786
BCF:   1.451
?
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:   3.936
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.717
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.015
?
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
NPO3803 Ardisia japonica Species Primulaceae Eukaryota whole plants Sendai, Miyagi Prefecture, Japan 2000-Sep PMID[17243725]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. whole plant n.a. PMID[17243725]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. whole plant n.a. PMID[17397219]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. twig n.a. PMID[21973101]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota aerial parts Kego Nature Reserve, Hatinh Province, Vietnam 2008-DEC PMID[21973101]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. Kego Nature Reserve, Hatinh Province, Vietnam 2008-DEC PMID[21973101]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. inflorescence n.a. PMID[21973101]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. leaf n.a. PMID[21973101]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. stem n.a. PMID[21973101]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[22940450]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota leaves, twigs, and fruits Nui Chua National Park (11 43' N; 109 08' E; 730 m alt.), Ninh Thuan Province, Vietnam 2010-Jan PMID[23301897]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[31621322]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO992 Betula alnoides Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1912 Acanthosyris paulo-alvinii Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5657 Oocystis polymorpha Species Oocystaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61 Phoebe grandis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6614 Rubus pileatus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3803 Ardisia japonica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6614 Rubus pileatus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5657 Oocystis polymorpha Species Oocystaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2846 Piper sarmentosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO992 Betula alnoides Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO61 Phoebe grandis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1912 Acanthosyris paulo-alvinii Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3803 Ardisia japonica Species Primulaceae 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
NPT115 Organism Mycobacterium tuberculosis H37Ra Mycobacterium tuberculosis H37Ra MIC = 50.0 ug.mL-1 PMID[22280816]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 50.0 ug.mL-1 PMID[28628823]

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 NPC159150 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
0.9 High Similarity NPC193673
0.8824 High Similarity NPC230698
0.8824 High Similarity NPC99078
0.8824 High Similarity NPC96406
0.8654 High Similarity NPC103947
0.8654 High Similarity NPC45783
0.8491 Intermediate Similarity NPC73883
0.8491 Intermediate Similarity NPC251454
0.7818 Intermediate Similarity NPC328419
0.7679 Intermediate Similarity NPC220923
0.7679 Intermediate Similarity NPC196609
0.75 Intermediate Similarity NPC94280
0.7358 Intermediate Similarity NPC255817
0.7358 Intermediate Similarity NPC136330
0.7091 Intermediate Similarity NPC205178
0.7091 Intermediate Similarity NPC227218
0.7059 Intermediate Similarity NPC217574
0.6923 Remote Similarity NPC167096
0.6923 Remote Similarity NPC605721
0.6842 Remote Similarity NPC318862
0.6786 Remote Similarity NPC194359
0.6786 Remote Similarity NPC28641
0.6786 Remote Similarity NPC180647
0.6786 Remote Similarity NPC225745
0.6207 Remote Similarity NPC248505
0.6182 Remote Similarity NPC470707
0.5862 Remote Similarity NPC252107
0.5763 Remote Similarity NPC69670
0.5556 Remote Similarity NPC114845
0.5538 Remote Similarity NPC270811
0.5538 Remote Similarity NPC471073
0.541 Remote Similarity NPC145446
0.541 Remote Similarity NPC137172
0.5303 Remote Similarity NPC170583
0.5254 Remote Similarity NPC469808
0.5231 Remote Similarity NPC95366
0.5231 Remote Similarity NPC152186
0.52 Remote Similarity NPC127326
0.5152 Remote Similarity NPC156944

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC159150 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
0.7358 Intermediate Similarity NPD2492 Phase 2

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