Natural Product: NPC481303

Natural Product IDNPC481303
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NAGFIUAMMBWFJS-ZULIBDNHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 NAGFIUAMMBWFJS-ZULIBDNHSA-N
Standard InCHI InChI=1S/C15H20O7/c1-2-3-8-4-5-10(9(17)6-8)21-15-14(20)13(19)12(18)11(7-16)22-15/h2-6,11-20H,7H2,1H3/b3-2+/t11-,12-,13+,14-,15-/m1/s1
SMILES C/C=C/c1ccc(c(c1)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.12 Volume:   301.869
?
Van der Waals volume.
Dense:   1.034 LogP:   0.677
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.174
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.41
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   119.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.513 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.704 Fsp3:   0.467
MCE-18:   48.364
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.386 Fluc inhibitor:   0.621
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.065
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.166
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.441 Promiscuous compounds:   0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.835 MDCK Permeability:   -5.189
Pgp-inhibitor:   0.0 Pgp-substrate:   0.085
PAMPA:   0.871
?
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):   0.298
20% Bioavailability (F20%):   0.341 30% Bioavailability (F30%):   0.952
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.035 MRP1:   0.176
Plasma Protein Binding (PPB):   82.243% Volume Distribution (VD):   -0.361
Fu: 17.072%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.05
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.399
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.932
HLM stability:   0.1
?
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):  3.031 Half-life (T1/2):  2.627

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.131
Human Hepatotoxicity (H-HT):  0.665 Drug-induced Liver Injury (DILI):  0.634
AMES Toxicity:  0.823 Rat Oral Acute Toxicity:  0.021
Maximum Recommended Daily Dose:  0.021 Skin Sensitization:  0.998
Carcinogencity:  0.285 Eye Corrosion:  0.002
Eye Irritation:  0.626 Respiratory Toxicity:  0.025
Drug-induced Neurotoxicity:  0.012 Ototoxicity:  0.855
Hematotoxicity:  0.235 Drug-induced Nephrotoxicity:  0.596
Genotoxicity:  0.103 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.236 Hek293 Cytotoxicity:  0.161
BCF:   0.703
?
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:   3.173
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.062
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.091
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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
NPO18983 Cleidion brevipetiolatum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[31419126]
NPO18983 Cleidion brevipetiolatum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18983 Cleidion brevipetiolatum 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 = 29200.0 nM PMID[31419126]

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 NPC481303 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
0.8182 Intermediate Similarity NPC100389
0.7895 Intermediate Similarity NPC202700
0.7368 Intermediate Similarity NPC59324
0.7308 Intermediate Similarity NPC200092
0.7288 Intermediate Similarity NPC186418
0.6964 Remote Similarity NPC19470
0.6667 Remote Similarity NPC310064
0.6515 Remote Similarity NPC488085
0.6296 Remote Similarity NPC9248
0.625 Remote Similarity NPC98777
0.6111 Remote Similarity NPC476864
0.6102 Remote Similarity NPC205054
0.6102 Remote Similarity NPC604356
0.6027 Remote Similarity NPC476866
0.6 Remote Similarity NPC26080
0.6 Remote Similarity NPC210015
0.6 Remote Similarity NPC165686
0.597 Remote Similarity NPC88043
0.5857 Remote Similarity NPC232228
0.5789 Remote Similarity NPC476865
0.5781 Remote Similarity NPC65530
0.5758 Remote Similarity NPC106944
0.5735 Remote Similarity NPC186406
0.5692 Remote Similarity NPC185778
0.5652 Remote Similarity NPC191046
0.5645 Remote Similarity NPC248355
0.5614 Remote Similarity NPC60589
0.5614 Remote Similarity NPC469708
0.5588 Remote Similarity NPC116229
0.5588 Remote Similarity NPC606353
0.5574 Remote Similarity NPC251102
0.5574 Remote Similarity NPC210298
0.5571 Remote Similarity NPC72249
0.5556 Remote Similarity NPC55040
0.5556 Remote Similarity NPC25292
0.5538 Remote Similarity NPC294166
0.5538 Remote Similarity NPC115022
0.5536 Remote Similarity NPC294470
0.55 Remote Similarity NPC310661
0.5469 Remote Similarity NPC302378
0.5455 Remote Similarity NPC212729
0.5455 Remote Similarity NPC142319
0.5455 Remote Similarity NPC604095
0.5455 Remote Similarity NPC604498
0.5441 Remote Similarity NPC259767
0.5424 Remote Similarity NPC221090
0.5397 Remote Similarity NPC105827
0.5385 Remote Similarity NPC26928
0.5357 Remote Similarity NPC269242
0.5357 Remote Similarity NPC484157
0.5342 Remote Similarity NPC292443
0.5333 Remote Similarity NPC166168
0.5333 Remote Similarity NPC214454
0.5323 Remote Similarity NPC479028
0.5323 Remote Similarity NPC479031
0.5303 Remote Similarity NPC242028
0.5303 Remote Similarity NPC203230
0.5303 Remote Similarity NPC252169
0.5303 Remote Similarity NPC174377
0.5303 Remote Similarity NPC469661
0.5294 Remote Similarity NPC189115
0.5294 Remote Similarity NPC212770
0.5283 Remote Similarity NPC228907
0.5263 Remote Similarity NPC192810
0.5254 Remote Similarity NPC12308
0.5246 Remote Similarity NPC40377
0.5246 Remote Similarity NPC9912
0.5238 Remote Similarity NPC214910
0.5238 Remote Similarity NPC210478
0.5231 Remote Similarity NPC85799
0.5231 Remote Similarity NPC473045
0.5231 Remote Similarity NPC303422
0.5231 Remote Similarity NPC218003
0.5231 Remote Similarity NPC97326
0.5224 Remote Similarity NPC8497
0.5217 Remote Similarity NPC57587
0.5211 Remote Similarity NPC45400
0.5205 Remote Similarity NPC145319
0.5161 Remote Similarity NPC232880
0.5161 Remote Similarity NPC49074
0.5156 Remote Similarity NPC479029
0.5152 Remote Similarity NPC157554
0.5135 Remote Similarity NPC481307
0.5132 Remote Similarity NPC476867
0.5128 Remote Similarity NPC476868
0.5085 Remote Similarity NPC609376
0.5079 Remote Similarity NPC162093
0.5079 Remote Similarity NPC270849
0.5079 Remote Similarity NPC23084
0.5077 Remote Similarity NPC222455
0.5077 Remote Similarity NPC599943
0.5072 Remote Similarity NPC475084

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481303 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