Natural Product: NPC200743

Natural Product IDNPC200743
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Polysin
IUPAC Name n.a.
Synonyms Polysin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1083627
PubChem CID 46871703
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles

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 NEPLKJAINOWIJL-DHNNRRLOSA-N
Standard InCHI InChI=1S/C23H29NO/c1-21(2)18-9-12-23(4)19(22(18,3)11-10-20(21)25)14-16-13-15-7-5-6-8-17(15)24(16)23/h5-8,13,18-19H,9-12,14H2,1-4H3/t18-,19-,22-,23+/m0/s1
SMILES CC1(C)[C@@H]2CC[C@]3(C)[C@@H](Cc4cc5ccccc5n34)[C@@]2(C)CCC1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   335.22 Volume:   370.187
?
Van der Waals volume.
Dense:   0.906 LogP:   3.377
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.322
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.29
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   22.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.637 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.201 Fsp3:   0.609
MCE-18:   109.757
?
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:   0.433 Fluc inhibitor:   0.118
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.107
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.013
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.061 Promiscuous compounds:   0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.513 MDCK Permeability:   -4.631
Pgp-inhibitor:   0.952 Pgp-substrate:   0.01
PAMPA:   0.039
?
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%):   0.017 30% Bioavailability (F30%):   0.316
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.226 MRP1:   0.861
Plasma Protein Binding (PPB):   95.339% Volume Distribution (VD):   0.558
Fu: 4.324%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.882
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.349 CYP1A2-substrate:   0.835
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.391
CYP2C9-inhibitor:   0.201 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.969
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.178
?
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):  8.749 Half-life (T1/2):  0.254

ADMET: Toxicity

hERG Blockers:  0.151 hERG Blockers (10um):  0.549
Human Hepatotoxicity (H-HT):  0.697 Drug-induced Liver Injury (DILI):  0.288
AMES Toxicity:  0.596 Rat Oral Acute Toxicity:  0.614
Maximum Recommended Daily Dose:  0.821 Skin Sensitization:  0.59
Carcinogencity:  0.915 Eye Corrosion:  0.004
Eye Irritation:  0.535 Respiratory Toxicity:  0.738
Drug-induced Neurotoxicity:  0.789 Ototoxicity:  0.504
Hematotoxicity:  0.435 Drug-induced Nephrotoxicity:  0.64
Genotoxicity:  0.921 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.247 Hek293 Cytotoxicity:  0.586
BCF:   2.339
?
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:   4.4
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.686
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.324
?
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
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO4501 Caragana intermedia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15620236]
NPO16473 Araucaria bidwillii Species Araucariaceae Eukaryota n.a. n.a. n.a. PMID[36542210]
NPO25009 Cystoseira myrica Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[36827158]
NPO24939 Veronica officinalis Species Plantaginaceae Eukaryota n.a. n.a. n.a. PMID[37765408]
NPO16473 Araucaria bidwillii Species Araucariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14893 Streptomyces eurocidicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21816 Calea jamaicensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24939 Veronica officinalis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28729 Spirostachys africana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24561 Sesuvium portulacastrum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24342 Lupinus albus Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16473 Araucaria bidwillii Species Araucariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16473 Araucaria bidwillii Species Araucariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12599.1 Pinus leiophylla var. chihuahuana Varieties Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23170 Orobanche coerulescens Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14893 Streptomyces eurocidicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO24723 Ophiorrhiza bracteata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21816 Calea jamaicensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25164 Polyalthia suaveolens Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24593 Campanula pyramidalis Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16473 Araucaria bidwillii Species Araucariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24561 Sesuvium portulacastrum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25009 Cystoseira myrica Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4501 Caragana intermedia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24939 Veronica officinalis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13718 Poria tenuis Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24123 Ramalina scopulorum Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28729 Spirostachys africana Species Euphorbiaceae 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
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Ki = 9000.0 nM PMID[20529682]
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Ki/Km = 0.05 n.a. PMID[20529682]

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 NPC200743 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
0.6818 Remote Similarity NPC126492

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC200743 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