Natural Product: NPC483847

Natural Product IDNPC483847
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GBINUJIXNLRFDG-BBJMFWAYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 134147873
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 GBINUJIXNLRFDG-BBJMFWAYSA-N
Standard InCHI InChI=1S/C26H34O8/c1-14-12-13-18(31-15(2)27)25(6)22(33-23(30)17-10-8-7-9-11-17)20(29)19-21(32-16(3)28)26(14,25)34-24(19,4)5/h7-11,14,18-22,29H,12-13H2,1-6H3/t14-,18+,19-,20-,21-,22-,25+,26-/m1/s1
SMILES C[C@@H]1CC[C@@H]([C@@]2(C)[C@@H]([C@@H]([C@@H]3[C@H]([C@]12OC3(C)C)OC(=O)C)O)OC(=O)c1ccccc1)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   474.23 Volume:   478.529
?
Van der Waals volume.
Dense:   0.991 LogP:   1.965
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.16
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.611
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   23.0
TPSA:   108.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.524 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.646 Fsp3:   0.654
MCE-18:   139.86
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.445 Fluc inhibitor:   0.038
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
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:   0.09 Promiscuous compounds:   0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.259 MDCK Permeability:   -4.782
Pgp-inhibitor:   0.993 Pgp-substrate:   0.542
PAMPA:   0.579
?
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):   0.001
20% Bioavailability (F20%):   0.148 30% Bioavailability (F30%):   0.58
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.158 MRP1:   0.993
Plasma Protein Binding (PPB):   70.714% Volume Distribution (VD):   -0.322
Fu: 31.363%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.566
BSEP inhibitor:   0.929

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.334
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.029
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.392
?
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):  7.544 Half-life (T1/2):  0.741

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.425
Human Hepatotoxicity (H-HT):  0.278 Drug-induced Liver Injury (DILI):  0.604
AMES Toxicity:  0.34 Rat Oral Acute Toxicity:  0.168
Maximum Recommended Daily Dose:  0.122 Skin Sensitization:  0.928
Carcinogencity:  0.663 Eye Corrosion:  0.021
Eye Irritation:  0.713 Respiratory Toxicity:  0.087
Drug-induced Neurotoxicity:  0.116 Ototoxicity:  0.385
Hematotoxicity:  0.062 Drug-induced Nephrotoxicity:  0.38
Genotoxicity:  0.415 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.057 Hek293 Cytotoxicity:  0.206
BCF:   0.559
?
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:   3.425
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.151
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.548
?
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
NPO40494 Maytenus bilocularis Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[27120798]

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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition > 30.0 % PMID[27120798]

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 NPC483847 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
0.931 High Similarity NPC475759
0.931 High Similarity NPC470152
0.7826 Intermediate Similarity NPC475122
0.7727 Intermediate Similarity NPC306146
0.7727 Intermediate Similarity NPC483841
0.7619 Intermediate Similarity NPC607964
0.7077 Intermediate Similarity NPC275592
0.7015 Intermediate Similarity NPC291599
0.6615 Remote Similarity NPC474608
0.6418 Remote Similarity NPC211137
0.6418 Remote Similarity NPC66761
0.6418 Remote Similarity NPC483843
0.6364 Remote Similarity NPC283375
0.6119 Remote Similarity NPC183122
0.6087 Remote Similarity NPC118080
0.5972 Remote Similarity NPC471101
0.5942 Remote Similarity NPC475429
0.5942 Remote Similarity NPC476094
0.5897 Remote Similarity NPC605086
0.5797 Remote Similarity NPC100913
0.5775 Remote Similarity NPC97947
0.5694 Remote Similarity NPC163087
0.5616 Remote Similarity NPC48017
0.5541 Remote Similarity NPC483842
0.5479 Remote Similarity NPC17877
0.5479 Remote Similarity NPC87448
0.5467 Remote Similarity NPC473758
0.5455 Remote Similarity NPC210591
0.5443 Remote Similarity NPC475039
0.5443 Remote Similarity NPC476035
0.5405 Remote Similarity NPC246480
0.5405 Remote Similarity NPC90257
0.5405 Remote Similarity NPC483845
0.5405 Remote Similarity NPC69357
0.5385 Remote Similarity NPC475652
0.5375 Remote Similarity NPC4421
0.5366 Remote Similarity NPC488916
0.5352 Remote Similarity NPC301556
0.5333 Remote Similarity NPC483846
0.5286 Remote Similarity NPC147561
0.525 Remote Similarity NPC29704
0.525 Remote Similarity NPC470157
0.5244 Remote Similarity NPC611111
0.52 Remote Similarity NPC483883
0.52 Remote Similarity NPC151585
0.5195 Remote Similarity NPC483844
0.519 Remote Similarity NPC472568
0.5135 Remote Similarity NPC90614
0.5128 Remote Similarity NPC252314

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483847 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