Natural Product: NPC485550

Natural Product IDNPC485550
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ICHOEKDQGHSBSI-VFCLNGDNSA-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]
    • [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 ICHOEKDQGHSBSI-VFCLNGDNSA-N
Standard InCHI InChI=1S/C20H34O3/c1-18(2)16-6-5-13-11-14(12-21)20(4,23)10-7-15(13)19(16,3)9-8-17(18)22/h11,14-17,21-23H,5-10,12H2,1-4H3/t14-,15-,16-,17-,19+,20+/m1/s1
SMILES CC1(C)[C@H]2CCC3=C[C@H](CO)[C@](C)(CC[C@H]3[C@]2(C)CC[C@H]1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.25 Volume:   352.541
?
Van der Waals volume.
Dense:   0.914 LogP:   2.415
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.588
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.132
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.649 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.581 Fsp3:   0.9
MCE-18:   61.737
?
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:   0.339 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
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:   0.551 Promiscuous compounds:   0.287

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.586 MDCK Permeability:   -5.1
Pgp-inhibitor:   0.164 Pgp-substrate:   0.517
PAMPA:   0.968
?
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):   0.108
20% Bioavailability (F20%):   0.525 30% Bioavailability (F30%):   0.449
50% Bioavailability (F50%):   0.934

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.192 MRP1:   0.716
Plasma Protein Binding (PPB):   72.813% Volume Distribution (VD):   -0.215
Fu: 24.876%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.361
BSEP inhibitor:   0.652

ADMET: Metabolism

CYP1A2-inhibitor:   0.305 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.972 CYP2C19-substrate:   0.047
CYP2C9-inhibitor:   0.371 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.031
CYP3A4-inhibitor:   0.011 CYP3A4-substrate:   0.975
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.075
HLM stability:   0.075
?
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):  10.086 Half-life (T1/2):  1.257

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.111
Human Hepatotoxicity (H-HT):  0.718 Drug-induced Liver Injury (DILI):  0.119
AMES Toxicity:  0.469 Rat Oral Acute Toxicity:  0.33
Maximum Recommended Daily Dose:  0.442 Skin Sensitization:  0.996
Carcinogencity:  0.846 Eye Corrosion:  0.023
Eye Irritation:  0.861 Respiratory Toxicity:  0.641
Drug-induced Neurotoxicity:  0.108 Ototoxicity:  0.501
Hematotoxicity:  0.188 Drug-induced Nephrotoxicity:  0.616
Genotoxicity:  0.149 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.754 Hek293 Cytotoxicity:  0.265
BCF:   1.059
?
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:   3.291
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.679
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.006
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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
NPO26395 Siegesbeckia pubescens Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[28009521]
NPO26395 Siegesbeckia pubescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 10000.0 nM PMID[28009521]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 100000.0 nM PMID[28009521]

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 NPC485550 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
0.6154 Remote Similarity NPC485549
0.5769 Remote Similarity NPC66566
0.5769 Remote Similarity NPC11829
0.5769 Remote Similarity NPC477923
0.5741 Remote Similarity NPC48362
0.5283 Remote Similarity NPC477138
0.5102 Remote Similarity NPC144650

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485550 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