Natural Product: NPC599976

Natural Product IDNPC599976
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LLLIKVGWTVPYAL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3039144
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 LLLIKVGWTVPYAL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O4/c1-19-12-5-3-4-11(8-12)17-10-15(18)14-9-13(20-2)6-7-16(14)21-17/h3-10H,1-2H3
SMILES COc1cccc(-c2cc(=O)c3cc(OC)ccc3o2)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   282.09 Volume:   290.988
?
Van der Waals volume.
Dense:   0.969 LogP:   2.881
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.991
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.251
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.888 Fsp3:   0.118
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:   0.481 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.981
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.834
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.609 Promiscuous compounds:   0.949

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.581 MDCK Permeability:   -4.522
Pgp-inhibitor:   0.968 Pgp-substrate:   0.062
PAMPA:   0.028
?
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):   0.067
20% Bioavailability (F20%):   0.166 30% Bioavailability (F30%):   0.163
50% Bioavailability (F50%):   0.866

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.566
Plasma Protein Binding (PPB):   92.758% Volume Distribution (VD):   -0.177
Fu: 4.816%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.995
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.885 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.812
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.782
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.438
CYP2B6-substrate:   0.442 CYP2C8-inhibitor:   0.751
HLM stability:   0.982
?
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):  7.763 Half-life (T1/2):  0.895

ADMET: Toxicity

hERG Blockers:  0.177 hERG Blockers (10um):  0.422
Human Hepatotoxicity (H-HT):  0.456 Drug-induced Liver Injury (DILI):  0.915
AMES Toxicity:  0.71 Rat Oral Acute Toxicity:  0.373
Maximum Recommended Daily Dose:  0.735 Skin Sensitization:  0.138
Carcinogencity:  0.879 Eye Corrosion:  0.303
Eye Irritation:  0.978 Respiratory Toxicity:  0.772
Drug-induced Neurotoxicity:  0.45 Ototoxicity:  0.113
Hematotoxicity:  0.373 Drug-induced Nephrotoxicity:  0.347
Genotoxicity:  0.941 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.129 Hek293 Cytotoxicity:  0.483
BCF:   1.424
?
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:   4.002
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.995
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.611
?
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
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[21049973]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45769 Primula decora Genus Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19812 Pimelea simplex Species Thymelaeaceae 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
NPT2816 Individual protein Bromodomain-containing protein 4 Homo sapiens Inhibition = 4.26 % PMID[34908415]
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 120.39 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 131.7 % PMID[23571415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 50000.0 nM PMID[34908415]
NPT784 Cell line MDA-MB-468 Homo sapiens IC50 > 50000.0 nM PMID[34908415]
NPT28438 Unchecked Unchecked n.a. log(ratio) = -0.09 n.a. PMID[35576701]
NPT22915 Protein family Casein kinase 2 Homo sapiens Inhibition = 10.37 % PMID[34908415]
NPT29337 Protein family Cytochrome P450 Homo sapiens Inhibition < 15.0 % PMID[35576701]

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 NPC599976 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
0.8085 Intermediate Similarity NPC607644
0.78 Intermediate Similarity NPC608264
0.6167 Remote Similarity NPC130015
0.6167 Remote Similarity NPC602126
0.5926 Remote Similarity NPC2771
0.5926 Remote Similarity NPC483772
0.5893 Remote Similarity NPC77955
0.5636 Remote Similarity NPC284424
0.5636 Remote Similarity NPC93653
0.5536 Remote Similarity NPC333230
0.5357 Remote Similarity NPC603094
0.5345 Remote Similarity NPC113089
0.5345 Remote Similarity NPC125887
0.5273 Remote Similarity NPC41721
0.5254 Remote Similarity NPC604085
0.5179 Remote Similarity NPC604293
0.5172 Remote Similarity NPC23955
0.5085 Remote Similarity NPC483774

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC599976 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