Natural Product: NPC603596

Natural Product IDNPC603596
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TWMBFWDMMIGYEO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL350720
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 TWMBFWDMMIGYEO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-12-5-4-9(6-13(12)23-2)17-18(24-3)16(21)15-11(20)7-10(19)8-14(15)25-17/h4-8,19-20H,1-3H3
SMILES COc1ccc(-c2oc3cc(O)cc(O)c3c(=O)c2OC)cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   2.535
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.361
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.683
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   98.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.751 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.305 Fsp3:   0.167
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.21 Fluc inhibitor:   0.413
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.872
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.699
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.34 Promiscuous compounds:   0.777

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.152 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.903 Pgp-substrate:   0.389
PAMPA:   0.067
?
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):   0.095
20% Bioavailability (F20%):   0.03 30% Bioavailability (F30%):   0.32
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.695
Plasma Protein Binding (PPB):   97.473% Volume Distribution (VD):   -0.143
Fu: 2.084%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.124
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.998
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.986 CYP1A2-substrate:   0.009
CYP2C19-inhibitor:   0.076 CYP2C19-substrate:   0.254
CYP2C9-inhibitor:   0.527 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.5 CYP3A4-substrate:   0.188
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.973
?
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):  5.15 Half-life (T1/2):  1.353

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.482
Human Hepatotoxicity (H-HT):  0.408 Drug-induced Liver Injury (DILI):  0.73
AMES Toxicity:  0.552 Rat Oral Acute Toxicity:  0.439
Maximum Recommended Daily Dose:  0.647 Skin Sensitization:  0.493
Carcinogencity:  0.792 Eye Corrosion:  0.692
Eye Irritation:  0.993 Respiratory Toxicity:  0.768
Drug-induced Neurotoxicity:  0.112 Ototoxicity:  0.097
Hematotoxicity:  0.153 Drug-induced Nephrotoxicity:  0.063
Genotoxicity:  0.83 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.553
BCF:   1.082
?
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:   3.735
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.418
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.956
?
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
NPO1119 Pulicaria canariensis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15844941]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[32372353]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[33588649]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[37849964]
NPO49758 Eucryphia lucida Species Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63478 Betula nigra Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63039 Eriodictyon trichocalyx Species Namaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56776 Barbacenia conicostigma Genus Velloziaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44053 Barbacenia rubro-virens Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49717 Cistus spp. Genus Cistaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25093 Ericameria diffusa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45016 Eucryphia Genus Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58693 Eucryphia milliganii Species Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20678 Grindelia nana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58025 Grindelia robusta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42491 Iochroma warscewiczii Genus Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55492 Mimulus lewisii Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51583 Petunia surfinia Genus Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51642 Siegesbeckia jorullensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1119 Pulicaria canariensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7897 Passiflora foetida Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28508 Flourensia cernua Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28508 Flourensia cernua Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28508 Flourensia cernua Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28508 Flourensia cernua Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1119 Pulicaria canariensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7897 Passiflora foetida Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25093 Ericameria diffusa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20678 Grindelia nana 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
NPT137 Cell line L1210 Mus musculus Activity n.a. n.a. n.a. PMID[469554]
NPT139 Cell line HT-29 Homo sapiens Activity = 74.2 n.a. PMID[15828817]
NPT139 Cell line HT-29 Homo sapiens Caspase induction = 1.1 n.a. PMID[15828817]
NPT139 Cell line HT-29 Homo sapiens Activity = 87.9 n.a. PMID[15828817]
NPT29317 Organism Enterovirus C Enterovirus C Minimal dose = 2.5 ug ml-1 PMID[1847431]

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
Enterovirus C Enterovirus C Max non-toxic dose = 50.0 ug ml-1 PMID[1847431]

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 NPC603596 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 NPC59951
0.7925 Intermediate Similarity NPC610359
0.7636 Intermediate Similarity NPC82325
0.75 Intermediate Similarity NPC162351
0.7407 Intermediate Similarity NPC184536
0.7407 Intermediate Similarity NPC103342
0.7368 Intermediate Similarity NPC279989
0.7321 Intermediate Similarity NPC115798
0.7321 Intermediate Similarity NPC159103
0.7273 Intermediate Similarity NPC286342
0.7193 Intermediate Similarity NPC236769
0.7193 Intermediate Similarity NPC12200
0.7091 Intermediate Similarity NPC123886
0.6724 Remote Similarity NPC176300
0.6441 Remote Similarity NPC178854
0.6333 Remote Similarity NPC7846
0.6333 Remote Similarity NPC605494
0.619 Remote Similarity NPC158874
0.6167 Remote Similarity NPC54394
0.6102 Remote Similarity NPC241838
0.6094 Remote Similarity NPC99671
0.6034 Remote Similarity NPC259058
0.5932 Remote Similarity NPC219330
0.5882 Remote Similarity NPC470458
0.5882 Remote Similarity NPC269285
0.5846 Remote Similarity NPC269906
0.5833 Remote Similarity NPC231772
0.5833 Remote Similarity NPC62536
0.5821 Remote Similarity NPC97255
0.5806 Remote Similarity NPC52005
0.5806 Remote Similarity NPC200316
0.5806 Remote Similarity NPC606638
0.5806 Remote Similarity NPC609179
0.5781 Remote Similarity NPC605634
0.5763 Remote Similarity NPC472438
0.5738 Remote Similarity NPC9609
0.5692 Remote Similarity NPC76482
0.5667 Remote Similarity NPC203891
0.5667 Remote Similarity NPC299923
0.5667 Remote Similarity NPC262094
0.5667 Remote Similarity NPC310259
0.5645 Remote Similarity NPC29841
0.5588 Remote Similarity NPC259632
0.5588 Remote Similarity NPC183
0.5574 Remote Similarity NPC50403
0.5574 Remote Similarity NPC28274
0.5574 Remote Similarity NPC76376
0.5526 Remote Similarity NPC609478
0.5507 Remote Similarity NPC56786
0.5479 Remote Similarity NPC470461
0.5469 Remote Similarity NPC133953
0.5469 Remote Similarity NPC125062
0.5467 Remote Similarity NPC472459
0.5455 Remote Similarity NPC603082
0.541 Remote Similarity NPC266960
0.5397 Remote Similarity NPC50728
0.5397 Remote Similarity NPC270620
0.5397 Remote Similarity NPC166753
0.5397 Remote Similarity NPC255350
0.5395 Remote Similarity NPC219904
0.5393 Remote Similarity NPC477895
0.5352 Remote Similarity NPC280493
0.5333 Remote Similarity NPC201547
0.5325 Remote Similarity NPC120099
0.5323 Remote Similarity NPC214138
0.5323 Remote Similarity NPC110070
0.5323 Remote Similarity NPC146679
0.5323 Remote Similarity NPC120464
0.5323 Remote Similarity NPC163524
0.5323 Remote Similarity NPC483773
0.5323 Remote Similarity NPC601901
0.5312 Remote Similarity NPC25495
0.5312 Remote Similarity NPC206604
0.5312 Remote Similarity NPC604422
0.5256 Remote Similarity NPC223747
0.5246 Remote Similarity NPC607530
0.5238 Remote Similarity NPC600900
0.5231 Remote Similarity NPC183950
0.5231 Remote Similarity NPC34725
0.5231 Remote Similarity NPC78326
0.5222 Remote Similarity NPC48984
0.52 Remote Similarity NPC470460
0.52 Remote Similarity NPC64305
0.5195 Remote Similarity NPC175107
0.519 Remote Similarity NPC203050
0.519 Remote Similarity NPC225434
0.5167 Remote Similarity NPC179271
0.5161 Remote Similarity NPC287979
0.5161 Remote Similarity NPC103904
0.5156 Remote Similarity NPC300943
0.5156 Remote Similarity NPC253634
0.5152 Remote Similarity NPC483775
0.5147 Remote Similarity NPC153512
0.5139 Remote Similarity NPC54802
0.5139 Remote Similarity NPC197304
0.5079 Remote Similarity NPC149127
0.5079 Remote Similarity NPC32557
0.5079 Remote Similarity NPC260895
0.5079 Remote Similarity NPC176665
0.5079 Remote Similarity NPC188871
0.5079 Remote Similarity NPC101830
0.5077 Remote Similarity NPC224137
0.5077 Remote Similarity NPC104459
0.5077 Remote Similarity NPC195202
0.5077 Remote Similarity NPC236223
0.5077 Remote Similarity NPC603112
0.5068 Remote Similarity NPC288084
0.5068 Remote Similarity NPC276222
0.5068 Remote Similarity NPC274618
0.5068 Remote Similarity NPC118284
0.5068 Remote Similarity NPC608147
0.5067 Remote Similarity NPC104677
0.5065 Remote Similarity NPC216496
0.5065 Remote Similarity NPC325555
0.5065 Remote Similarity NPC226304
0.5063 Remote Similarity NPC88023
0.5063 Remote Similarity NPC309025

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603596 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
0.5397 Remote Similarity NPD2801 Pre-clinical

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