Natural Product: NPC603112

Natural Product IDNPC603112
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TUEHVMYACGCKDL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1094586
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 TUEHVMYACGCKDL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O8/c1-23-12-6-5-9(7-10(12)20)16-19(26-4)15(22)14-11(21)8-13(24-2)17(25-3)18(14)27-16/h5-8,20-21H,1-4H3
SMILES COc1ccc(-c2oc3c(OC)c(OC)cc(O)c3c(=O)c2OC)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   360.741
?
Van der Waals volume.
Dense:   1.037 LogP:   2.311
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.352
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.151
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   107.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.494 Fsp3:   0.211
MCE-18:   20.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.146 Fluc inhibitor:   0.342
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.873
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.636
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.328 Promiscuous compounds:   0.512

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.216 MDCK Permeability:   -4.749
Pgp-inhibitor:   0.715 Pgp-substrate:   0.15
PAMPA:   0.1
?
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):   0.076
20% Bioavailability (F20%):   0.074 30% Bioavailability (F30%):   0.259
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.874
Plasma Protein Binding (PPB):   96.4% Volume Distribution (VD):   -0.427
Fu: 2.87%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.501
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.946
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   0.1
CYP2C19-inhibitor:   0.527 CYP2C19-substrate:   0.208
CYP2C9-inhibitor:   0.702 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.874 CYP2D6-substrate:   0.587
CYP3A4-inhibitor:   0.974 CYP3A4-substrate:   0.438
CYP2B6-substrate:   0.009 CYP2C8-inhibitor:   0.637
HLM stability:   0.951
?
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):  4.349 Half-life (T1/2):  1.865

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.492
Human Hepatotoxicity (H-HT):  0.454 Drug-induced Liver Injury (DILI):  0.723
AMES Toxicity:  0.494 Rat Oral Acute Toxicity:  0.403
Maximum Recommended Daily Dose:  0.415 Skin Sensitization:  0.584
Carcinogencity:  0.743 Eye Corrosion:  0.236
Eye Irritation:  0.954 Respiratory Toxicity:  0.753
Drug-induced Neurotoxicity:  0.201 Ototoxicity:  0.196
Hematotoxicity:  0.309 Drug-induced Nephrotoxicity:  0.213
Genotoxicity:  0.341 RPMI-8226 Immunitoxicity:  0.142
A549 Cytotoxicity:  0.218 Hek293 Cytotoxicity:  0.349
BCF:   1.059
?
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:   3.478
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.433
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.832
?
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
NPO28215 Centaurea africana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56203 Ricinocarpos muricatus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50771 Ricinocarpos stylosus Genus Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO64091 Solanum paludosum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28215 Centaurea africana Species Asteraceae 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
NPT91 Cell line KB Homo sapiens Activity = 9.0 % PMID[20356063]
NPT28438 Unchecked Unchecked n.a. Inhibition = 0.0 % PMID[20356063]

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 NPC603112 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
0.7925 Intermediate Similarity NPC32557
0.7778 Intermediate Similarity NPC607913
0.7636 Intermediate Similarity NPC178854
0.7407 Intermediate Similarity NPC189960
0.7368 Intermediate Similarity NPC152166
0.7273 Intermediate Similarity NPC605144
0.7193 Intermediate Similarity NPC4481
0.7018 Intermediate Similarity NPC270620
0.7018 Intermediate Similarity NPC265511
0.7 Intermediate Similarity NPC603082
0.6724 Remote Similarity NPC204854
0.6441 Remote Similarity NPC82325
0.6333 Remote Similarity NPC25495
0.6271 Remote Similarity NPC9609
0.6167 Remote Similarity NPC300943
0.5833 Remote Similarity NPC176665
0.5738 Remote Similarity NPC86485
0.5738 Remote Similarity NPC603827
0.5667 Remote Similarity NPC262094
0.5645 Remote Similarity NPC605582
0.5574 Remote Similarity NPC143828
0.5556 Remote Similarity NPC235215
0.5556 Remote Similarity NPC236769
0.5556 Remote Similarity NPC7846
0.5556 Remote Similarity NPC605494
0.55 Remote Similarity NPC245546
0.5484 Remote Similarity NPC22472
0.541 Remote Similarity NPC306821
0.5397 Remote Similarity NPC200740
0.5397 Remote Similarity NPC253634
0.5323 Remote Similarity NPC301123
0.5323 Remote Similarity NPC188871
0.5312 Remote Similarity NPC189179
0.5312 Remote Similarity NPC196439
0.5312 Remote Similarity NPC223579
0.5312 Remote Similarity NPC206604
0.5231 Remote Similarity NPC19687
0.5231 Remote Similarity NPC78326
0.5161 Remote Similarity NPC103904
0.5161 Remote Similarity NPC292107
0.5147 Remote Similarity NPC99671
0.5125 Remote Similarity NPC265115
0.5079 Remote Similarity NPC59951
0.5079 Remote Similarity NPC105242
0.5079 Remote Similarity NPC76376
0.5079 Remote Similarity NPC130894
0.5079 Remote Similarity NPC146679
0.5079 Remote Similarity NPC606763
0.5077 Remote Similarity NPC78302
0.5077 Remote Similarity NPC603596

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603112 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