Natural Product: NPC481065

Natural Product IDNPC481065
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RMMGXDAHEJFECG-GHZUSETOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132487992
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0002051] Agarofurans

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 RMMGXDAHEJFECG-GHZUSETOSA-N
Standard InCHI InChI=1S/C29H34O5/c1-19-15-16-23(32-25(30)20-11-7-5-8-12-20)28(4)24(33-26(31)21-13-9-6-10-14-21)17-22-18-29(19,28)34-27(22,2)3/h5-14,19,22-24H,15-18H2,1-4H3/t19-,22-,23+,24+,28+,29+/m1/s1
SMILES C[C@@H]1CC[C@@H]([C@@]2(C)[C@H](C[C@@H]3C[C@]12OC3(C)C)OC(=O)c1ccccc1)OC(=O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.24 Volume:   490.217
?
Van der Waals volume.
Dense:   0.943 LogP:   4.622
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.963
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.616
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   28.0
TPSA:   61.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.535 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.201 Fsp3:   0.517
MCE-18:   144.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.784 Fluc inhibitor:   0.486
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.045
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.05

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.896 MDCK Permeability:   -4.618
Pgp-inhibitor:   1.0 Pgp-substrate:   0.231
PAMPA:   0.086
?
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):   0.0
20% Bioavailability (F20%):   0.131 30% Bioavailability (F30%):   0.251
50% Bioavailability (F50%):   0.815

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.354 MRP1:   0.999
Plasma Protein Binding (PPB):   96.884% Volume Distribution (VD):   -0.022
Fu: 2.684%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.439 BCRP inhibitor:   0.171
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.021
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   0.828
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.092
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.893
?
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):  6.724 Half-life (T1/2):  0.326

ADMET: Toxicity

hERG Blockers:  0.124 hERG Blockers (10um):  0.733
Human Hepatotoxicity (H-HT):  0.113 Drug-induced Liver Injury (DILI):  0.756
AMES Toxicity:  0.331 Rat Oral Acute Toxicity:  0.283
Maximum Recommended Daily Dose:  0.463 Skin Sensitization:  0.969
Carcinogencity:  0.776 Eye Corrosion:  0.022
Eye Irritation:  0.752 Respiratory Toxicity:  0.302
Drug-induced Neurotoxicity:  0.729 Ototoxicity:  0.253
Hematotoxicity:  0.045 Drug-induced Nephrotoxicity:  0.729
Genotoxicity:  0.262 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.415 Hek293 Cytotoxicity:  0.512
BCF:   1.438
?
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:   4.49
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.378
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.248
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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
NPO40471 Celastrus subspicata Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[28548851]

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
NPT2 Others Unspecified n.a. IC50 = 27600.0 nM PMID[28548851]

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 NPC481065 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
0.9038 High Similarity NPC147561
0.8 Intermediate Similarity NPC66985
0.6949 Remote Similarity NPC481066
0.6667 Remote Similarity NPC156077
0.5846 Remote Similarity NPC473869
0.5846 Remote Similarity NPC84129
0.5775 Remote Similarity NPC36021
0.5625 Remote Similarity NPC283375
0.5625 Remote Similarity NPC183122
0.5625 Remote Similarity NPC474608
0.5538 Remote Similarity NPC100913
0.5522 Remote Similarity NPC483879
0.5455 Remote Similarity NPC475429
0.5455 Remote Similarity NPC476094
0.5417 Remote Similarity NPC214550
0.5333 Remote Similarity NPC276735
0.5303 Remote Similarity NPC301556
0.5195 Remote Similarity NPC483872
0.5072 Remote Similarity NPC475759

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481065 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