Natural Product: NPC600900

Natural Product IDNPC600900
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZYVBPTWKKGRSOZ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2296064
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 ZYVBPTWKKGRSOZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O8/c1-23-15-7-10(17(24-2)19(26-4)18(15)25-3)13-8-12(22)16-11(21)5-9(20)6-14(16)27-13/h5-8,20-21H,1-4H3
SMILES COc1cc(-c2cc(=O)c3c(O)cc(O)cc3o2)c(OC)c(OC)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   360.741
?
Van der Waals volume.
Dense:   1.037 LogP:   2.191
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.049
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.877
?
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:   2.566 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:   0 PAINS Alert:   0
Colloidal aggregators:   0.155 Fluc inhibitor:   0.254
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.804
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.566
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.347 Promiscuous compounds:   0.843

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.202 MDCK Permeability:   -4.795
Pgp-inhibitor:   0.161 Pgp-substrate:   0.284
PAMPA:   0.05
?
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):   0.002
20% Bioavailability (F20%):   0.129 30% Bioavailability (F30%):   0.522
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.214 MRP1:   0.978
Plasma Protein Binding (PPB):   96.705% Volume Distribution (VD):   -0.283
Fu: 2.613%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.653
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.984
BSEP inhibitor:   0.89

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.06
CYP2C19-inhibitor:   0.046 CYP2C19-substrate:   0.027
CYP2C9-inhibitor:   0.59 CYP2C9-substrate:   0.517
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.346 CYP3A4-substrate:   0.122
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.976
HLM stability:   0.778
?
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):  4.326 Half-life (T1/2):  1.184

ADMET: Toxicity

hERG Blockers:  0.101 hERG Blockers (10um):  0.575
Human Hepatotoxicity (H-HT):  0.398 Drug-induced Liver Injury (DILI):  0.759
AMES Toxicity:  0.446 Rat Oral Acute Toxicity:  0.434
Maximum Recommended Daily Dose:  0.706 Skin Sensitization:  0.641
Carcinogencity:  0.782 Eye Corrosion:  0.569
Eye Irritation:  0.991 Respiratory Toxicity:  0.819
Drug-induced Neurotoxicity:  0.159 Ototoxicity:  0.11
Hematotoxicity:  0.161 Drug-induced Nephrotoxicity:  0.052
Genotoxicity:  0.633 RPMI-8226 Immunitoxicity:  0.115
A549 Cytotoxicity:  0.281 Hek293 Cytotoxicity:  0.708
BCF:   1.268
?
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:   3.417
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.541
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.741
?
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
NPO25700 Psiadia punctulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25700 Psiadia punctulata 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
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 15.0 ug.mL-1 DOI[10.1007/s00044-013-0485-8]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 7.4 ug.mL-1 DOI[10.1007/s00044-013-0485-8]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 48.0 ug.mL-1 DOI[10.1007/s00044-013-0485-8]

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 NPC600900 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
0.7885 Intermediate Similarity NPC62536
0.6909 Remote Similarity NPC120464
0.6909 Remote Similarity NPC483773
0.6842 Remote Similarity NPC12200
0.6842 Remote Similarity NPC606638
0.6607 Remote Similarity NPC231772
0.6607 Remote Similarity NPC601901
0.6441 Remote Similarity NPC183950
0.6271 Remote Similarity NPC52005
0.625 Remote Similarity NPC183
0.614 Remote Similarity NPC219330
0.6034 Remote Similarity NPC610359
0.5968 Remote Similarity NPC605634
0.5942 Remote Similarity NPC63454
0.5942 Remote Similarity NPC183851
0.5893 Remote Similarity NPC274121
0.5818 Remote Similarity NPC50898
0.5818 Remote Similarity NPC78540
0.5789 Remote Similarity NPC213216
0.5789 Remote Similarity NPC600022
0.5714 Remote Similarity NPC175013
0.5676 Remote Similarity NPC101731
0.5614 Remote Similarity NPC279121
0.5593 Remote Similarity NPC605617
0.5574 Remote Similarity NPC328119
0.55 Remote Similarity NPC33265
0.5424 Remote Similarity NPC610974
0.5395 Remote Similarity NPC172202
0.5395 Remote Similarity NPC284127
0.5385 Remote Similarity NPC84324
0.5345 Remote Similarity NPC607658
0.5323 Remote Similarity NPC159103
0.5278 Remote Similarity NPC272064
0.5246 Remote Similarity NPC78341
0.5246 Remote Similarity NPC28274
0.5238 Remote Similarity NPC162351
0.5238 Remote Similarity NPC603596
0.5238 Remote Similarity NPC609179
0.5211 Remote Similarity NPC150908
0.5211 Remote Similarity NPC600972
0.5195 Remote Similarity NPC88023
0.5195 Remote Similarity NPC309025
0.5185 Remote Similarity NPC476410
0.5167 Remote Similarity NPC75279
0.5156 Remote Similarity NPC133953
0.5139 Remote Similarity NPC290830
0.5139 Remote Similarity NPC71061
0.5139 Remote Similarity NPC72425
0.5139 Remote Similarity NPC303485
0.5082 Remote Similarity NPC123886
0.5082 Remote Similarity NPC184536
0.5082 Remote Similarity NPC103342
0.5079 Remote Similarity NPC608498
0.507 Remote Similarity NPC134796
0.5068 Remote Similarity NPC186227

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600900 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
0.5614 Remote Similarity NPD1511 Phase 2

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