Natural Product: NPC488570

Natural Product IDNPC488570
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LJSZZGXUGKBJHC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 LJSZZGXUGKBJHC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H22O6/c1-13(2)7-8-27-15-10-17(23)21-20(11-15)28-12-16(22(21)24)14-5-6-18(25-3)19(9-14)26-4/h5-7,9-12,23H,8H2,1-4H3
SMILES CC(=CCOc1cc(c2c(c1)occ(c1ccc(c(c1)OC)OC)c2=O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.14 Volume:   392.412
?
Van der Waals volume.
Dense:   0.974 LogP:   4.048
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.208
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.1
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.631 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.501 Fsp3:   0.227
MCE-18:   19.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.6 Fluc inhibitor:   0.641
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.901
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.632
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.252 Promiscuous compounds:   0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.738 MDCK Permeability:   -4.616
Pgp-inhibitor:   0.878 Pgp-substrate:   0.354
PAMPA:   0.139
?
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):   0.083
20% Bioavailability (F20%):   0.094 30% Bioavailability (F30%):   0.442
50% Bioavailability (F50%):   0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.933
Plasma Protein Binding (PPB):   96.489% Volume Distribution (VD):   0.183
Fu: 2.707%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.855
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.992
BSEP inhibitor:   0.963

ADMET: Metabolism

CYP1A2-inhibitor:   0.946 CYP1A2-substrate:   0.927
CYP2C19-inhibitor:   0.17 CYP2C19-substrate:   0.602
CYP2C9-inhibitor:   0.98 CYP2C9-substrate:   0.028
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.38
CYP3A4-inhibitor:   0.091 CYP3A4-substrate:   0.94
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.989
HLM stability:   0.948
?
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):  6.763 Half-life (T1/2):  1.186

ADMET: Toxicity

hERG Blockers:  0.277 hERG Blockers (10um):  0.637
Human Hepatotoxicity (H-HT):  0.562 Drug-induced Liver Injury (DILI):  0.916
AMES Toxicity:  0.526 Rat Oral Acute Toxicity:  0.427
Maximum Recommended Daily Dose:  0.561 Skin Sensitization:  0.569
Carcinogencity:  0.735 Eye Corrosion:  0.005
Eye Irritation:  0.823 Respiratory Toxicity:  0.833
Drug-induced Neurotoxicity:  0.272 Ototoxicity:  0.307
Hematotoxicity:  0.323 Drug-induced Nephrotoxicity:  0.339
Genotoxicity:  0.507 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.156 Hek293 Cytotoxicity:  0.302
BCF:   1.676
?
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:   4.295
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.573
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.029
?
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
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]

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
NPT34 Cell line BV-2 Mus musculus IC50 > 50000.0 nM PMID[29482940]

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 NPC488570 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
0.8548 High Similarity NPC133400
0.8254 Intermediate Similarity NPC249824
0.8226 Intermediate Similarity NPC203636
0.7463 Intermediate Similarity NPC479305
0.7015 Intermediate Similarity NPC185401
0.6667 Remote Similarity NPC116632
0.6364 Remote Similarity NPC200316
0.6176 Remote Similarity NPC114192
0.6061 Remote Similarity NPC303644
0.5857 Remote Similarity NPC254741
0.5811 Remote Similarity NPC280937
0.557 Remote Similarity NPC233502
0.5522 Remote Similarity NPC185607
0.5507 Remote Similarity NPC471590
0.5467 Remote Similarity NPC474993
0.5385 Remote Similarity NPC469404
0.5362 Remote Similarity NPC294409
0.5362 Remote Similarity NPC490701
0.5352 Remote Similarity NPC90665
0.5309 Remote Similarity NPC604503
0.5256 Remote Similarity NPC488567
0.5244 Remote Similarity NPC189270
0.5244 Remote Similarity NPC5840
0.5224 Remote Similarity NPC195919
0.5211 Remote Similarity NPC12377
0.5205 Remote Similarity NPC104728
0.5128 Remote Similarity NPC253822
0.5122 Remote Similarity NPC487213
0.507 Remote Similarity NPC166753
0.5065 Remote Similarity NPC233918
0.5062 Remote Similarity NPC160515
0.506 Remote Similarity NPC73511
0.5059 Remote Similarity NPC484041

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488570 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