Natural Product: NPC473352

Natural Product IDNPC473352
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Xerophilusin N
IUPAC Name n.a.
Synonyms Xerophilusin N
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL402260
PubChem CID 44445776
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 CGLKYUSLUAHYRT-JKFOIHFYSA-N
Standard InCHI InChI=1S/C20H26O6/c1-9-10-5-6-11-18-8-4-7-17(2,3)12(18)15(23)20(25,26-16(18)24)19(11,13(9)21)14(10)22/h10-12,14-15,22-23,25H,1,4-8H2,2-3H3/t10-,11-,12+,14+,15-,18+,19-,20-/m0/s1
SMILES CC1(CCCC23C1C(C(C45C2CCC(C4O)C(=C)C5=O)(OC3=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   356.526
?
Van der Waals volume.
Dense:   1.016 LogP:   1.613
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.065
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.534
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   104.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.437 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.86 Fsp3:   0.8
MCE-18:   132.222
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.019 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.049
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.115 Promiscuous compounds:   0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.064 MDCK Permeability:   -4.801
Pgp-inhibitor:   0.008 Pgp-substrate:   0.037
PAMPA:   0.984
?
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):   0.925
20% Bioavailability (F20%):   0.191 30% Bioavailability (F30%):   0.944
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.886
Plasma Protein Binding (PPB):   67.725% Volume Distribution (VD):   -0.142
Fu: 37.636%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.848
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.006
BSEP inhibitor:   0.28

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.019 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.973 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.085 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.024
HLM stability:   0.504
?
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):  3.916 Half-life (T1/2):  2.44

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.324
Human Hepatotoxicity (H-HT):  0.761 Drug-induced Liver Injury (DILI):  0.349
AMES Toxicity:  0.454 Rat Oral Acute Toxicity:  0.465
Maximum Recommended Daily Dose:  0.926 Skin Sensitization:  0.142
Carcinogencity:  0.444 Eye Corrosion:  0.0
Eye Irritation:  0.011 Respiratory Toxicity:  0.487
Drug-induced Neurotoxicity:  0.39 Ototoxicity:  0.929
Hematotoxicity:  0.28 Drug-induced Nephrotoxicity:  0.37
Genotoxicity:  0.843 RPMI-8226 Immunitoxicity:  0.15
A549 Cytotoxicity:  0.074 Hek293 Cytotoxicity:  0.646
BCF:   1.396
?
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:   4.048
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.759
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.02
?
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
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[10843567]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17665952]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[21534539]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota aerial parts Shangrila, Yunnan Province, China 2008-AUG PMID[21534539]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[33325237]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8404 Isodon xerophilus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18055 Isodon adenolomus Species Lamiaceae 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
NPT111 Cell line K562 Homo sapiens IC50 = 1200.0 nM PMID[26317881]
NPT1097 Cell line MKN-45 Homo sapiens IC50 = 4800.0 nM DrugMatrix in vitro pharmacology data
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[21524582]
NPT116 Cell line HL-60 Homo sapiens IC50 = 3800.0 nM PMID[11076565]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 = 3600.0 nM PMID[11076565]
NPT81 Cell line A549 Homo sapiens IC50 = 9700.0 nM PMID[11076565]
NPT83 Cell line MCF7 Homo sapiens IC50 = 7900.0 nM PMID[18321710]
NPT660 Cell line SW480 Homo sapiens IC50 = 3500.0 nM PMID[18321710]

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 NPC473352 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
0.5938 Remote Similarity NPC88945
0.5833 Remote Similarity NPC55973
0.5833 Remote Similarity NPC471461
0.5833 Remote Similarity NPC89860
0.5833 Remote Similarity NPC189663
0.5833 Remote Similarity NPC153234
0.5714 Remote Similarity NPC471244
0.5714 Remote Similarity NPC471093
0.5625 Remote Similarity NPC145625
0.5625 Remote Similarity NPC102741
0.5614 Remote Similarity NPC471241
0.5484 Remote Similarity NPC471476
0.5484 Remote Similarity NPC473324
0.5455 Remote Similarity NPC471245
0.5397 Remote Similarity NPC63244
0.5397 Remote Similarity NPC122339
0.5385 Remote Similarity NPC132668
0.5238 Remote Similarity NPC488144
0.5238 Remote Similarity NPC483202
0.5231 Remote Similarity NPC488143
0.5161 Remote Similarity NPC252679
0.5161 Remote Similarity NPC118721
0.5156 Remote Similarity NPC488145
0.5152 Remote Similarity NPC488142
0.5152 Remote Similarity NPC213320

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473352 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