Natural Product: NPC475836

Natural Product IDNPC475836
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rautandiol A
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL517074
PubChem CID 11674519
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 MGXPFABBMNBNJN-CJESRSHOSA-N
Standard InCHI InChI=1S/C20H20O5/c1-20(2)18(22)6-10-5-13-16(8-15(10)25-20)23-9-14-12-4-3-11(21)7-17(12)24-19(13)14/h3-5,7-8,14,18-19,21-22H,6,9H2,1-2H3/t14-,18?,19-/m0/s1
SMILES CC1(C(CC2=CC3=C(C=C2O1)OCC4C3OC5=C4C=CC(=C5)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   339.826
?
Van der Waals volume.
Dense:   1.001 LogP:   2.689
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.621
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.123
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.771 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.949 Fsp3:   0.4
MCE-18:   96.0
?
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:   0.253 Fluc inhibitor:   0.074
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.41
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.255
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.22 Promiscuous compounds:   0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.851 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.001 Pgp-substrate:   0.678
PAMPA:   0.447
?
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):   0.005
20% Bioavailability (F20%):   0.677 30% Bioavailability (F30%):   0.611
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.719 MRP1:   0.964
Plasma Protein Binding (PPB):   91.134% Volume Distribution (VD):   0.195
Fu: 12.642%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.201
OATP1B3 inhibitor:   0.955 BCRP inhibitor:   0.62
BSEP inhibitor:   0.912

ADMET: Metabolism

CYP1A2-inhibitor:   0.109 CYP1A2-substrate:   0.794
CYP2C19-inhibitor:   0.967 CYP2C19-substrate:   0.535
CYP2C9-inhibitor:   0.75 CYP2C9-substrate:   0.069
CYP2D6-inhibitor:   0.659 CYP2D6-substrate:   0.358
CYP3A4-inhibitor:   0.936 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.647
HLM stability:   0.349
?
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):  6.792 Half-life (T1/2):  2.397

ADMET: Toxicity

hERG Blockers:  0.273 hERG Blockers (10um):  0.708
Human Hepatotoxicity (H-HT):  0.581 Drug-induced Liver Injury (DILI):  0.269
AMES Toxicity:  0.441 Rat Oral Acute Toxicity:  0.512
Maximum Recommended Daily Dose:  0.814 Skin Sensitization:  0.198
Carcinogencity:  0.625 Eye Corrosion:  0.001
Eye Irritation:  0.804 Respiratory Toxicity:  0.804
Drug-induced Neurotoxicity:  0.366 Ototoxicity:  0.774
Hematotoxicity:  0.118 Drug-induced Nephrotoxicity:  0.213
Genotoxicity:  0.495 RPMI-8226 Immunitoxicity:  0.035
A549 Cytotoxicity:  0.291 Hek293 Cytotoxicity:  0.755
BCF:   1.231
?
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:   3.646
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.581
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.557
?
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
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16562843]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24293 Neorautanenia mitis 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
NPT83 Cell line MCF7 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[16933872]
NPT81 Cell line A549 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[16933872]
NPT81 Cell line A549 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[28189086]

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 NPC475836 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
0.7302 Intermediate Similarity NPC101376
0.6984 Remote Similarity NPC474687
0.6825 Remote Similarity NPC236014
0.6418 Remote Similarity NPC296915
0.6316 Remote Similarity NPC471215
0.6316 Remote Similarity NPC262573
0.6032 Remote Similarity NPC32633
0.597 Remote Similarity NPC605244
0.5303 Remote Similarity NPC39064
0.5303 Remote Similarity NPC47283
0.5286 Remote Similarity NPC150011
0.5278 Remote Similarity NPC223008
0.5211 Remote Similarity NPC118114
0.5205 Remote Similarity NPC121925
0.5152 Remote Similarity NPC27495
0.5143 Remote Similarity NPC85264

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475836 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