Natural Product: NPC603109

Natural Product IDNPC603109
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OPAORDVBZRVVNQ-RNQWEJQRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2261562
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 OPAORDVBZRVVNQ-RNQWEJQRSA-N
Standard InCHI InChI=1S/C20H24O4/c1-13(9-15-5-7-17(21)19(11-15)23-3)14(2)10-16-6-8-18(22)20(12-16)24-4/h5-9,11-12,14,21-22H,10H2,1-4H3/b13-9-/t14-/m1/s1
SMILES COc1cc(/C=C(/C)[C@H](C)Cc2ccc(O)c(OC)c2)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   354.069
?
Van der Waals volume.
Dense:   0.927 LogP:   3.658
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.31
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.157
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   58.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.825 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.803 Fsp3:   0.3
MCE-18:   28.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.697 Fluc inhibitor:   0.924
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.137
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.093
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.658 Promiscuous compounds:   0.15

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.128 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.166 Pgp-substrate:   0.28
PAMPA:   0.004
?
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):   0.0
20% Bioavailability (F20%):   0.388 30% Bioavailability (F30%):   0.289
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.975
Plasma Protein Binding (PPB):   97.043% Volume Distribution (VD):   -0.2
Fu: 2.578%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.832
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.277 CYP1A2-substrate:   0.81
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.566 CYP2C9-substrate:   0.805
CYP2D6-inhibitor:   0.802 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.909
?
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):  8.497 Half-life (T1/2):  1.033

ADMET: Toxicity

hERG Blockers:  0.222 hERG Blockers (10um):  0.578
Human Hepatotoxicity (H-HT):  0.733 Drug-induced Liver Injury (DILI):  0.526
AMES Toxicity:  0.49 Rat Oral Acute Toxicity:  0.435
Maximum Recommended Daily Dose:  0.758 Skin Sensitization:  0.9
Carcinogencity:  0.333 Eye Corrosion:  0.148
Eye Irritation:  0.947 Respiratory Toxicity:  0.766
Drug-induced Neurotoxicity:  0.76 Ototoxicity:  0.301
Hematotoxicity:  0.198 Drug-induced Nephrotoxicity:  0.713
Genotoxicity:  0.504 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.41 Hek293 Cytotoxicity:  0.529
BCF:   1.442
?
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:   3.948
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.879
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.372
?
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
NPO1570 Guaiacum officinale Species Zygophyllaceae Eukaryota n.a. heartwood n.a. PMID[21391655]
NPO1570 Guaiacum officinale Species Zygophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1570 Guaiacum officinale 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
NPT68 Individual protein Aldose reductase Rattus norvegicus IC50 = 35481.34 nM DOI[10.1007/s00044-011-9681-6]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC603109 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
0.6364 Remote Similarity NPC165133
0.6364 Remote Similarity NPC242885
0.6364 Remote Similarity NPC95614
0.6364 Remote Similarity NPC232316
0.5965 Remote Similarity NPC90431
0.5814 Remote Similarity NPC156840
0.5745 Remote Similarity NPC85488
0.5686 Remote Similarity NPC127587
0.5652 Remote Similarity NPC473388
0.56 Remote Similarity NPC56214
0.56 Remote Similarity NPC487676
0.5517 Remote Similarity NPC110699
0.5517 Remote Similarity NPC106055
0.549 Remote Similarity NPC227217
0.549 Remote Similarity NPC117780
0.5455 Remote Similarity NPC246358
0.5435 Remote Similarity NPC8547
0.5435 Remote Similarity NPC36108
0.5435 Remote Similarity NPC233731
0.5435 Remote Similarity NPC610203
0.54 Remote Similarity NPC31344
0.54 Remote Similarity NPC317769
0.5333 Remote Similarity NPC485282
0.5333 Remote Similarity NPC485283
0.5333 Remote Similarity NPC485281
0.5306 Remote Similarity NPC299406
0.5217 Remote Similarity NPC257124
0.5167 Remote Similarity NPC487681
0.5106 Remote Similarity NPC221049
0.5106 Remote Similarity NPC140359
0.5102 Remote Similarity NPC57490
0.5102 Remote Similarity NPC71579
0.5094 Remote Similarity NPC276014

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603109 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
0.5217 Remote Similarity NPD228 Phase 0

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