Natural Product: NPC602026

Natural Product IDNPC602026
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KJRQQECDVUXBCO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL441526
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 KJRQQECDVUXBCO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O4/c1-19-14-9-8-12-13(18)10-15(11-6-4-3-5-7-11)21-16(12)17(14)20-2/h3-10H,1-2H3
SMILES COc1ccc2c(=O)cc(-c3ccccc3)oc2c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   282.09 Volume:   290.988
?
Van der Waals volume.
Dense:   0.969 LogP:   3.052
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.022
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.152
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   48.67
?
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:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.976 Fsp3:   0.118
MCE-18:   16.0
?
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:   0.149 Fluc inhibitor:   0.839
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.942
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.75
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.544 Promiscuous compounds:   0.67

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.606 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.972 Pgp-substrate:   0.036
PAMPA:   0.137
?
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):   0.003
20% Bioavailability (F20%):   0.08 30% Bioavailability (F30%):   0.213
50% Bioavailability (F50%):   0.601

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.518 MRP1:   0.951
Plasma Protein Binding (PPB):   98.435% Volume Distribution (VD):   -0.049
Fu: 0.984%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.958
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.905
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.482 CYP1A2-substrate:   0.971
CYP2C19-inhibitor:   0.909 CYP2C19-substrate:   0.291
CYP2C9-inhibitor:   0.834 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.541 CYP2D6-substrate:   0.068
CYP3A4-inhibitor:   0.954 CYP3A4-substrate:   0.985
CYP2B6-substrate:   0.157 CYP2C8-inhibitor:   0.996
HLM stability:   0.777
?
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):  5.032 Half-life (T1/2):  1.515

ADMET: Toxicity

hERG Blockers:  0.153 hERG Blockers (10um):  0.471
Human Hepatotoxicity (H-HT):  0.515 Drug-induced Liver Injury (DILI):  0.882
AMES Toxicity:  0.607 Rat Oral Acute Toxicity:  0.472
Maximum Recommended Daily Dose:  0.656 Skin Sensitization:  0.36
Carcinogencity:  0.84 Eye Corrosion:  0.217
Eye Irritation:  0.947 Respiratory Toxicity:  0.67
Drug-induced Neurotoxicity:  0.466 Ototoxicity:  0.139
Hematotoxicity:  0.39 Drug-induced Nephrotoxicity:  0.279
Genotoxicity:  0.883 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.136 Hek293 Cytotoxicity:  0.436
BCF:   1.369
?
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:   4.111
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.882
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.584
?
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
NPO11139 Godmania aesculifolia Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11139 Godmania aesculifolia Species Bignoniaceae 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
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens Inhibition = 5.97 % PMID[28049590]
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens Inhibition n.a. n.a. % PMID[28049590]
NPT1333 Individual protein Enoyl-acyl-carrier protein reductase Plasmodium falciparum Activity n.a. n.a. n.a. PMID[16722653]
NPT1332 Individual protein Fatty acid synthase Plasmodium falciparum Activity n.a. n.a. n.a. PMID[16722653]
NPT1334 Individual protein 3-oxoacyl-acyl-carrier protein reductase Plasmodium falciparum Activity n.a. n.a. n.a. PMID[16722653]
NPT29338 Single protein BDNF/NT-3 growth factors receptor Rattus norvegicus Activity n.a. n.a. n.a. PMID[21073191]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense EC50 = 21600.0 nM PMID[30234295]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 40900.0 nM PMID[16722653]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Activity n.a. n.a. n.a. PMID[16722653]

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 NPC602026 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
0.75 Intermediate Similarity NPC136278
0.6667 Remote Similarity NPC60972
0.6471 Remote Similarity NPC284424
0.6111 Remote Similarity NPC306821
0.5962 Remote Similarity NPC607644
0.5536 Remote Similarity NPC488084
0.5536 Remote Similarity NPC205522
0.5472 Remote Similarity NPC41721
0.5455 Remote Similarity NPC129680
0.537 Remote Similarity NPC604293
0.5357 Remote Similarity NPC131624
0.5357 Remote Similarity NPC602963
0.5273 Remote Similarity NPC299582
0.5273 Remote Similarity NPC2771
0.5273 Remote Similarity NPC106461
0.5238 Remote Similarity NPC472408
0.5098 Remote Similarity NPC32298
0.5091 Remote Similarity NPC40818

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602026 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