Natural Product: NPC605144

Natural Product IDNPC605144
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IUKBSFKDMZKGMT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL165890
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 IUKBSFKDMZKGMT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-12-8-11(20)13-14(21)18(24-3)15(25-17(13)16(12)23-2)9-4-6-10(19)7-5-9/h4-8,19-20H,1-3H3
SMILES COc1cc(O)c2c(=O)c(OC)c(-c3ccc(O)cc3)oc2c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   2.453
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.372
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.844
?
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:   2.396 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:   0.155 Fluc inhibitor:   0.354
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.904
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.571
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.322 Promiscuous compounds:   0.726

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.079 MDCK Permeability:   -4.765
Pgp-inhibitor:   0.674 Pgp-substrate:   0.144
PAMPA:   0.363
?
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):   0.008
20% Bioavailability (F20%):   0.042 30% Bioavailability (F30%):   0.093
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.04 MRP1:   0.905
Plasma Protein Binding (PPB):   96.761% Volume Distribution (VD):   -0.252
Fu: 2.443%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.255
OATP1B3 inhibitor:   0.918 BCRP inhibitor:   0.918
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.702 CYP1A2-substrate:   0.124
CYP2C19-inhibitor:   0.306 CYP2C19-substrate:   0.276
CYP2C9-inhibitor:   0.113 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.891 CYP2D6-substrate:   0.912
CYP3A4-inhibitor:   0.524 CYP3A4-substrate:   0.164
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.966
HLM stability:   0.928
?
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):  7.414 Half-life (T1/2):  1.368

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.499
Human Hepatotoxicity (H-HT):  0.452 Drug-induced Liver Injury (DILI):  0.697
AMES Toxicity:  0.466 Rat Oral Acute Toxicity:  0.447
Maximum Recommended Daily Dose:  0.521 Skin Sensitization:  0.577
Carcinogencity:  0.76 Eye Corrosion:  0.182
Eye Irritation:  0.963 Respiratory Toxicity:  0.663
Drug-induced Neurotoxicity:  0.218 Ototoxicity:  0.169
Hematotoxicity:  0.205 Drug-induced Nephrotoxicity:  0.116
Genotoxicity:  0.754 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.208 Hek293 Cytotoxicity:  0.549
BCF:   1.239
?
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:   3.686
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.391
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.89
?
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
NPO25088 Larrea tridentata Species Zygophyllaceae Eukaryota n.a. n.a. n.a. PMID[12960376]
NPO25088 Larrea tridentata Species Zygophyllaceae Eukaryota n.a. n.a. n.a. PMID[2166136]
NPO51266 Fagonia bruguieri Species Zygophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52215 Cleome viscosa Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25088 Larrea tridentata Species Zygophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8790 Cyanostegia angustifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO64557 Ozothamnus spp. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49900 Cleome spinosa Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50771 Ricinocarpos stylosus Genus Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45545 Calceolaria chelidonioides Species Calceolariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56528 Calceolaria tripartita Species Calceolariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25088 Larrea tridentata Species Zygophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25088 Larrea tridentata Species Zygophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8790 Cyanostegia angustifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8790 Cyanostegia angustifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25088 Larrea tridentata Species Zygophyllaceae 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
NPT29317 Organism Enterovirus C Enterovirus C Minimal dose = 0.3 ug ml-1 PMID[1847431]
NPT29317 Organism Enterovirus C Enterovirus C Reduction factor = 1000000.0 n.a. PMID[1847431]
NPT29317 Organism Enterovirus C Enterovirus C ED99 = 0.25 ug ml-1 PMID[1847431]
NPT30043 Cell line Vero Chlorocebus sabaeus CyD50 > 100.0 ug ml-1 PMID[1847431]
NPT1538 Organism Human rhinovirus sp. Human rhinovirus sp. CyD50 > 100.0 ug ml-1 PMID[1847431]
NPT1538 Organism Human rhinovirus sp. Human rhinovirus sp. ED99 = 0.5 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 = 25.0 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 NPC605144 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
0.8235 Intermediate Similarity NPC607913
0.82 Intermediate Similarity NPC189960
0.8039 Intermediate Similarity NPC32557
0.7778 Intermediate Similarity NPC152166
0.7407 Intermediate Similarity NPC178854
0.7273 Intermediate Similarity NPC603112
0.7037 Intermediate Similarity NPC105242
0.7037 Intermediate Similarity NPC606763
0.678 Remote Similarity NPC603082
0.6727 Remote Similarity NPC146679
0.6545 Remote Similarity NPC191459
0.625 Remote Similarity NPC103342
0.614 Remote Similarity NPC101830
0.5965 Remote Similarity NPC266960
0.5862 Remote Similarity NPC176665
0.5789 Remote Similarity NPC245546
0.5763 Remote Similarity NPC22472
0.569 Remote Similarity NPC306821
0.569 Remote Similarity NPC292107
0.5667 Remote Similarity NPC178343
0.5667 Remote Similarity NPC253634
0.5593 Remote Similarity NPC301123
0.5593 Remote Similarity NPC188871
0.5593 Remote Similarity NPC143828
0.5517 Remote Similarity NPC136840
0.55 Remote Similarity NPC86485
0.5484 Remote Similarity NPC19687
0.5424 Remote Similarity NPC90582
0.5424 Remote Similarity NPC103904
0.5424 Remote Similarity NPC262094
0.5333 Remote Similarity NPC286342
0.5333 Remote Similarity NPC130894
0.5323 Remote Similarity NPC7846
0.5238 Remote Similarity NPC78326
0.5231 Remote Similarity NPC259411
0.5167 Remote Similarity NPC71334
0.5167 Remote Similarity NPC287979
0.5167 Remote Similarity NPC184536
0.5167 Remote Similarity NPC285144
0.5167 Remote Similarity NPC104700
0.5128 Remote Similarity NPC265115
0.5082 Remote Similarity NPC59951
0.5082 Remote Similarity NPC143799
0.5082 Remote Similarity NPC234133
0.5082 Remote Similarity NPC76376
0.5082 Remote Similarity NPC231018
0.5079 Remote Similarity NPC288669
0.5079 Remote Similarity NPC235215
0.5079 Remote Similarity NPC236769
0.5079 Remote Similarity NPC4481
0.5079 Remote Similarity NPC605494
0.5075 Remote Similarity NPC306488

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605144 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