Natural Product: NPC604085

Natural Product IDNPC604085
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RMPRESDCJMOAHW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1339927
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 RMPRESDCJMOAHW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O4/c1-19-12-5-2-10(3-6-12)16-9-14(18)13-8-11(17)4-7-15(13)20-16/h2-9,17H,1H3
SMILES COc1ccc(-c2cc(=O)c3cc(O)ccc3o2)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.07 Volume:   273.692
?
Van der Waals volume.
Dense:   0.979 LogP:   2.74
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.963
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.727
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.775 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.932 Fsp3:   0.062
MCE-18:   16.0
?
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:   0.534 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.993
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.839
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.797 Promiscuous compounds:   0.501

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.768 MDCK Permeability:   -4.693
Pgp-inhibitor:   0.298 Pgp-substrate:   0.147
PAMPA:   0.665
?
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):   0.103
20% Bioavailability (F20%):   0.644 30% Bioavailability (F30%):   0.525
50% Bioavailability (F50%):   0.937

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.024 MRP1:   0.756
Plasma Protein Binding (PPB):   94.786% Volume Distribution (VD):   -0.15
Fu: 4.968%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.864
BSEP inhibitor:   0.942

ADMET: Metabolism

CYP1A2-inhibitor:   0.64 CYP1A2-substrate:   0.966
CYP2C19-inhibitor:   0.368 CYP2C19-substrate:   0.184
CYP2C9-inhibitor:   0.898 CYP2C9-substrate:   0.672
CYP2D6-inhibitor:   0.989 CYP2D6-substrate:   0.755
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.818
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.913
?
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):  8.586 Half-life (T1/2):  1.01

ADMET: Toxicity

hERG Blockers:  0.146 hERG Blockers (10um):  0.434
Human Hepatotoxicity (H-HT):  0.464 Drug-induced Liver Injury (DILI):  0.815
AMES Toxicity:  0.672 Rat Oral Acute Toxicity:  0.384
Maximum Recommended Daily Dose:  0.738 Skin Sensitization:  0.287
Carcinogencity:  0.829 Eye Corrosion:  0.231
Eye Irritation:  0.982 Respiratory Toxicity:  0.754
Drug-induced Neurotoxicity:  0.317 Ototoxicity:  0.122
Hematotoxicity:  0.238 Drug-induced Nephrotoxicity:  0.193
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.149 Hek293 Cytotoxicity:  0.542
BCF:   1.313
?
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:   4.065
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.908
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.529
?
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
NPO49034 Pimelea decora Species Thymelaeaceae 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
NPT105 Individual protein Muscleblind-like protein 1 Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 1584.9 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 92.0 nM PubChem BioAssay data set
NPT157 Individual protein Breast cancer type 1 susceptibility protein Homo sapiens Potency n.a. 1258.9 nM PubChem BioAssay data set
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 316.2 nM PubChem BioAssay data set
NPT537 Individual protein Ras-related protein Rab-9A Homo sapiens Potency = 1584.9 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 4466.8 nM PubChem BioAssay data set
NPT29671 Protein complex group Nuclear factor NF-kappa-B complex Homo sapiens EC50 = 6991.0 nM PubChem BioAssay data set
NPT4770 Individual protein High-affinity choline transporter Homo sapiens IC50 n.a. 4383.69 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 1694.4 nM PubChem BioAssay data set
NPT4770 Individual protein High-affinity choline transporter Homo sapiens IC50 n.a. 3642.61 nM PubChem BioAssay data set
NPT538 Individual protein Niemann-Pick C1 protein Homo sapiens Potency = 1412.5 nM PubChem BioAssay data set
NPT28644 Nucleic-acid microRNA 21 Homo sapiens Potency = 414.0 nM PubChem BioAssay data set
NPT28599 Protein complex group Casein kinase II Homo sapiens IC50 = 30000.0 nM PMID[24011954]
NPT28599 Protein complex group Casein kinase II Homo sapiens Activity = 49.0 % PMID[24011954]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 7568.6 nM PubChem BioAssay data set
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 5802.4 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 4107.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 1471.6 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 5623.4 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 1778.3 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. IC50 = 78600.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. AC50 > 420000.0 nM PubChem BioAssay data set
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC > 32.0 ug.mL-1 PMID[31986405]
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set

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 NPC604085 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
0.7037 Intermediate Similarity NPC266597
0.6604 Remote Similarity NPC2771
0.625 Remote Similarity NPC125887
0.614 Remote Similarity NPC231772
0.614 Remote Similarity NPC250266
0.6111 Remote Similarity NPC604293
0.5965 Remote Similarity NPC156222
0.5965 Remote Similarity NPC29353
0.5862 Remote Similarity NPC184136
0.5862 Remote Similarity NPC57030
0.5862 Remote Similarity NPC22519
0.5862 Remote Similarity NPC145379
0.5818 Remote Similarity NPC607644
0.5763 Remote Similarity NPC603662
0.5645 Remote Similarity NPC295036
0.5574 Remote Similarity NPC604422
0.5574 Remote Similarity NPC607642
0.5484 Remote Similarity NPC610914
0.5439 Remote Similarity NPC101294
0.5424 Remote Similarity NPC274327
0.5424 Remote Similarity NPC52611
0.5424 Remote Similarity NPC600177
0.5357 Remote Similarity NPC22783
0.5357 Remote Similarity NPC12367
0.5345 Remote Similarity NPC14958
0.5333 Remote Similarity NPC176775
0.5333 Remote Similarity NPC234133
0.5333 Remote Similarity NPC604462
0.5323 Remote Similarity NPC605336
0.5323 Remote Similarity NPC606525
0.5254 Remote Similarity NPC599976
0.5172 Remote Similarity NPC284424
0.5167 Remote Similarity NPC77955
0.5167 Remote Similarity NPC241498
0.5167 Remote Similarity NPC483774
0.5167 Remote Similarity NPC47815
0.5167 Remote Similarity NPC608264
0.5161 Remote Similarity NPC20830
0.5085 Remote Similarity NPC333230
0.5082 Remote Similarity NPC198826
0.5082 Remote Similarity NPC281207
0.5082 Remote Similarity NPC120163
0.5082 Remote Similarity NPC605146
0.5079 Remote Similarity NPC115323
0.507 Remote Similarity NPC601984

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604085 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