Natural Product: NPC601901

Natural Product IDNPC601901
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ONKNGUOZRAKQPG-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3960030
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 ONKNGUOZRAKQPG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O7/c1-22-16-11(20)2-7(3-12(16)21)13-6-10(19)15-9(18)4-8(17)5-14(15)23-13/h2-6,17-18,20-21H,1H3
SMILES COc1c(O)cc(-c2cc(=O)c3c(O)cc(O)cc3o2)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.06 Volume:   300.063
?
Van der Waals volume.
Dense:   1.053 LogP:   2.019
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.017
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.507
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   120.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.572 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.639 Fsp3:   0.062
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.83 Fluc inhibitor:   0.664
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.68
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.568 Promiscuous compounds:   0.91

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.056 MDCK Permeability:   -4.807
Pgp-inhibitor:   0.026 Pgp-substrate:   0.608
PAMPA:   0.296
?
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):   0.005
20% Bioavailability (F20%):   0.236 30% Bioavailability (F30%):   0.87
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.038 MRP1:   0.872
Plasma Protein Binding (PPB):   93.764% Volume Distribution (VD):   -0.669
Fu: 3.887%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.739
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.949
BSEP inhibitor:   0.128

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.19
CYP2C19-inhibitor:   0.013 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.627
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.967
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.065
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.914
?
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):  3.71 Half-life (T1/2):  1.477

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.532
Human Hepatotoxicity (H-HT):  0.392 Drug-induced Liver Injury (DILI):  0.755
AMES Toxicity:  0.61 Rat Oral Acute Toxicity:  0.506
Maximum Recommended Daily Dose:  0.839 Skin Sensitization:  0.793
Carcinogencity:  0.675 Eye Corrosion:  0.423
Eye Irritation:  0.998 Respiratory Toxicity:  0.863
Drug-induced Neurotoxicity:  0.034 Ototoxicity:  0.093
Hematotoxicity:  0.06 Drug-induced Nephrotoxicity:  0.032
Genotoxicity:  0.954 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.521 Hek293 Cytotoxicity:  0.736
BCF:   0.862
?
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:   3.405
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.514
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.823
?
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
NPO50670 Asarina procumbens Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47926 Nonea pulla Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45870 Nonea lutea Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54320 Passiflora palmeri Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 37000.0 nM PMID[27955927]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 59300.0 nM PMID[27955927]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 112.0 % PMID[27955927]
NPT32 Organism Mus musculus Mus musculus Activity = 119.0 % PMID[27955927]





 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 NPC601901 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 NPC52005
0.7925 Intermediate Similarity NPC606638
0.7358 Intermediate Similarity NPC231772
0.7358 Intermediate Similarity NPC62536
0.7358 Intermediate Similarity NPC120464
0.7358 Intermediate Similarity NPC483773
0.717 Intermediate Similarity NPC123886
0.7143 Intermediate Similarity NPC183950
0.7059 Intermediate Similarity NPC175013
0.7037 Intermediate Similarity NPC50403
0.6964 Remote Similarity NPC12200
0.6607 Remote Similarity NPC600900
0.6604 Remote Similarity NPC279121
0.6538 Remote Similarity NPC50898
0.6538 Remote Similarity NPC78540
0.6102 Remote Similarity NPC162351
0.6102 Remote Similarity NPC609179
0.6094 Remote Similarity NPC183
0.6066 Remote Similarity NPC605634
0.6034 Remote Similarity NPC256283
0.5965 Remote Similarity NPC241498
0.5932 Remote Similarity NPC82325
0.5932 Remote Similarity NPC54394
0.5862 Remote Similarity NPC100887
0.5789 Remote Similarity NPC293183
0.5735 Remote Similarity NPC150908
0.5735 Remote Similarity NPC600972
0.5714 Remote Similarity NPC274121
0.569 Remote Similarity NPC284552
0.569 Remote Similarity NPC184536
0.569 Remote Similarity NPC156222
0.569 Remote Similarity NPC103342
0.569 Remote Similarity NPC605617
0.5652 Remote Similarity NPC290830
0.5652 Remote Similarity NPC71061
0.5652 Remote Similarity NPC72425
0.5652 Remote Similarity NPC303485
0.5614 Remote Similarity NPC213216
0.5593 Remote Similarity NPC286342
0.5593 Remote Similarity NPC59951
0.5593 Remote Similarity NPC610359
0.5574 Remote Similarity NPC177298
0.5574 Remote Similarity NPC223579
0.5571 Remote Similarity NPC63454
0.5571 Remote Similarity NPC183851
0.5571 Remote Similarity NPC272064
0.5571 Remote Similarity NPC186227
0.5538 Remote Similarity NPC112954
0.5517 Remote Similarity NPC610974
0.5493 Remote Similarity NPC215203
0.5484 Remote Similarity NPC133953
0.5484 Remote Similarity NPC279989
0.5424 Remote Similarity NPC301323
0.5424 Remote Similarity NPC219330
0.5417 Remote Similarity NPC601565
0.541 Remote Similarity NPC83508
0.541 Remote Similarity NPC255350
0.5405 Remote Similarity NPC191306
0.5373 Remote Similarity NPC34089
0.5373 Remote Similarity NPC196179
0.5362 Remote Similarity NPC134796
0.5333 Remote Similarity NPC241838
0.5333 Remote Similarity NPC234133
0.5333 Remote Similarity NPC28274
0.5333 Remote Similarity NPC188203
0.5323 Remote Similarity NPC287101
0.5323 Remote Similarity NPC603596
0.5323 Remote Similarity NPC607642
0.5303 Remote Similarity NPC301217
0.5263 Remote Similarity NPC88023
0.5263 Remote Similarity NPC172202
0.5263 Remote Similarity NPC284127
0.5263 Remote Similarity NPC309025
0.5254 Remote Similarity NPC131624
0.5246 Remote Similarity NPC108406
0.5238 Remote Similarity NPC125062
0.5205 Remote Similarity NPC265530
0.5167 Remote Similarity NPC127447
0.5167 Remote Similarity NPC29353
0.5167 Remote Similarity NPC600177
0.5161 Remote Similarity NPC212678
0.5161 Remote Similarity NPC159103
0.5152 Remote Similarity NPC138299
0.5152 Remote Similarity NPC111112
0.5147 Remote Similarity NPC254351
0.5132 Remote Similarity NPC101731
0.5128 Remote Similarity NPC600989
0.5082 Remote Similarity NPC33265
0.5082 Remote Similarity NPC184136
0.5082 Remote Similarity NPC48479
0.5079 Remote Similarity NPC160951
0.5075 Remote Similarity NPC291746
0.5072 Remote Similarity NPC224714
0.5072 Remote Similarity NPC603692
0.5072 Remote Similarity NPC610480
0.5068 Remote Similarity NPC143851
0.5065 Remote Similarity NPC165970
0.5063 Remote Similarity NPC84324

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC601901 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
0.6604 Remote Similarity NPD1511 Phase 2
0.541 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