Natural Product: NPC477356

Natural Product IDNPC477356
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WOQBUFGEWLXSNN-AHUQOVQWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1801687
PubChem CID 56662974
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 WOQBUFGEWLXSNN-AHUQOVQWSA-N
Standard InCHI InChI=1S/C22H32O5/c1-11-9-15-14(20(15,4)5)7-8-21(6)19(27-21)16-17(24)12(2)10-22(16,18(11)25)26-13(3)23/h9,12,14-17,19,24H,7-8,10H2,1-6H3/b11-9+/t12-,14-,15-,16+,17-,19+,21+,22+/m0/s1
SMILES C/C/1=C[C@H]2[C@H](CC[C@]3(C)[C@@H]([C@H]4[C@H]([C@@H](C)C[C@@]4(C1=O)OC(=O)C)O)O3)C2(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.22 Volume:   390.884
?
Van der Waals volume.
Dense:   0.962 LogP:   2.312
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.642
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.864
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   76.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.562 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.379 Fsp3:   0.818
MCE-18:   78.0
?
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:   0.826 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.17 Promiscuous compounds:   0.529

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.236 MDCK Permeability:   -5.004
Pgp-inhibitor:   0.879 Pgp-substrate:   0.057
PAMPA:   0.398
?
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):   0.014
20% Bioavailability (F20%):   0.623 30% Bioavailability (F30%):   0.402
50% Bioavailability (F50%):   0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.141 MRP1:   0.963
Plasma Protein Binding (PPB):   85.12% Volume Distribution (VD):   -0.056
Fu: 14.289%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.01
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.014 CYP1A2-substrate:   0.342
CYP2C19-inhibitor:   0.064 CYP2C19-substrate:   0.253
CYP2C9-inhibitor:   0.028 CYP2C9-substrate:   0.166
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.078
CYP3A4-inhibitor:   0.249 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.948
HLM stability:   0.984
?
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):  10.127 Half-life (T1/2):  1.275

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.259
Human Hepatotoxicity (H-HT):  0.625 Drug-induced Liver Injury (DILI):  0.727
AMES Toxicity:  0.785 Rat Oral Acute Toxicity:  0.342
Maximum Recommended Daily Dose:  0.544 Skin Sensitization:  0.963
Carcinogencity:  0.849 Eye Corrosion:  0.023
Eye Irritation:  0.783 Respiratory Toxicity:  0.438
Drug-induced Neurotoxicity:  0.298 Ototoxicity:  0.306
Hematotoxicity:  0.676 Drug-induced Nephrotoxicity:  0.764
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.173
A549 Cytotoxicity:  0.281 Hek293 Cytotoxicity:  0.61
BCF:   1.398
?
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:   3.844
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.182
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.726
?
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
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[12542364]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[19036584]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota stems Botanical Garden, Osmania University, Hyderabad, Andhra Pradesh 2006-AUG PMID[21534583]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[30817151]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO520 Euphorbia lathyris Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28682 Jatropha multifida Species Euphorbiaceae 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

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 > 100000.0 nM PMID[30817151]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 50000.0 nM PMID[30817151]
NPT177 Tissue Aorta Rattus norvegicus Activity < 30.0 % PMID[21534583]

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 NPC477356 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
0.7246 Intermediate Similarity NPC37968
0.7049 Intermediate Similarity NPC601506
0.6912 Remote Similarity NPC117417
0.65 Remote Similarity NPC87090
0.6133 Remote Similarity NPC482297
0.6032 Remote Similarity NPC482430
0.6 Remote Similarity NPC482348
0.5873 Remote Similarity NPC601088
0.5873 Remote Similarity NPC610420
0.5538 Remote Similarity NPC482431
0.5352 Remote Similarity NPC610678
0.5147 Remote Similarity NPC482196

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477356 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