Natural Product: NPC162419

Natural Product IDNPC162419
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MZQZXSHFWDHNOW-IONNQARKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10307877
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0002811] Phenylpropanes

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 MZQZXSHFWDHNOW-IONNQARKSA-N
Standard InCHI InChI=1S/C9H12O2/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9-11H,1H3/t7-,9+/m0/s1
SMILES C[C@@H]([C@H](c1ccccc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   152.08 Volume:   165.335
?
Van der Waals volume.
Dense:   0.92 LogP:   1.004
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.092
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.097
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.666 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.449 Fsp3:   0.333
MCE-18:   12.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.145 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.007
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.812 Promiscuous compounds:   0.35

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.551 MDCK Permeability:   -4.591
Pgp-inhibitor:   0.01 Pgp-substrate:   0.227
PAMPA:   0.817
?
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%):   0.03 30% Bioavailability (F30%):   0.186
50% Bioavailability (F50%):   0.469

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.639 MRP1:   0.474
Plasma Protein Binding (PPB):   44.784% Volume Distribution (VD):   0.246
Fu: 48.19%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.587
OATP1B3 inhibitor:   0.855 BCRP inhibitor:   0.089
BSEP inhibitor:   0.151

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.109 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.423
HLM stability:   0.904
?
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):  6.295 Half-life (T1/2):  3.944

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.382
Human Hepatotoxicity (H-HT):  0.708 Drug-induced Liver Injury (DILI):  0.008
AMES Toxicity:  0.285 Rat Oral Acute Toxicity:  0.085
Maximum Recommended Daily Dose:  0.179 Skin Sensitization:  0.715
Carcinogencity:  0.1 Eye Corrosion:  0.176
Eye Irritation:  0.972 Respiratory Toxicity:  0.034
Drug-induced Neurotoxicity:  0.388 Ototoxicity:  0.399
Hematotoxicity:  0.04 Drug-induced Nephrotoxicity:  0.121
Genotoxicity:  0.152 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.132 Hek293 Cytotoxicity:  0.083
BCF:   0.238
?
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:   2.369
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.577
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.729
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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
NPO9046 Aigialus parvus Species Aigialaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO14259 Euphorbia milii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5283 Schefflera actinophylla Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15162 Henricia sanguinolenta Species Echinasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9046 Aigialus parvus Species Aigialaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14259 Euphorbia milii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14259 Euphorbia milii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13752 Acacia mollissima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17993 Antitrogus parvulus Species Scarabaeidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9046 Aigialus parvus Species Aigialaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14259 Euphorbia milii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO640 Gloriosa modesta Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5283 Schefflera actinophylla Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13752 Acacia mollissima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6091 Gluta usitata Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15162 Henricia sanguinolenta Species Echinasteridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12172 Bauerella baueri n.a. n.a. n.a. 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

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 NPC162419 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
0.7 Intermediate Similarity NPC103326
0.7 Intermediate Similarity NPC99394
0.7 Intermediate Similarity NPC87299
0.5833 Remote Similarity NPC329319
0.5417 Remote Similarity NPC330967
0.5385 Remote Similarity NPC164514
0.5385 Remote Similarity NPC303611
0.5385 Remote Similarity NPC108606
0.5385 Remote Similarity NPC290515
0.5385 Remote Similarity NPC226096
0.5312 Remote Similarity NPC489737
0.5172 Remote Similarity NPC251306

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC162419 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
0.5385 Remote Similarity NPD9611 Phase 4
0.5385 Remote Similarity NPD9612 Approved
0.52 Remote Similarity NPD9395 Phase 4
0.5185 Remote Similarity NPD9609 Approved

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