Natural Product: NPC236716

Natural Product IDNPC236716
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WHRDRHNMTIXZNY-CJZVHFPTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 92043456
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003782] Kaurane 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 WHRDRHNMTIXZNY-CJZVHFPTSA-N
Standard InCHI InChI=1S/C20H26O6/c1-8-9-4-5-10-18-11(21)6-7-17(2,3)12(18)14(23)20(24)19(10,13(8)22)15(9)25-16(18)26-20/h9-12,14-16,21,23-24H,1,4-7H2,2-3H3/t9?,10-,11-,12+,14-,15-,16-,18-,19-,20+/m0/s1
SMILES C=C1C2CC[C@H]3[C@]45[C@H](CCC(C)(C)[C@H]4[C@@H]([C@@]4([C@@]3(C1=O)[C@H]2O[C@H]5O4)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   350.606
?
Van der Waals volume.
Dense:   1.033 LogP:   1.222
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.679
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.871
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   26.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   8.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.55 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.491 Fsp3:   0.85
MCE-18:   148.622
?
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:   0.189 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.172 Promiscuous compounds:   0.401

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.079 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.005 Pgp-substrate:   0.364
PAMPA:   0.962
?
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):   0.386
20% Bioavailability (F20%):   0.561 30% Bioavailability (F30%):   0.919
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.026 MRP1:   0.71
Plasma Protein Binding (PPB):   44.3% Volume Distribution (VD):   -0.235
Fu: 54.446%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.111
BSEP inhibitor:   0.419

ADMET: Metabolism

CYP1A2-inhibitor:   0.157 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.891 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.091 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.454 CYP2D6-substrate:   0.075
CYP3A4-inhibitor:   0.01 CYP3A4-substrate:   0.835
CYP2B6-substrate:   0.581 CYP2C8-inhibitor:   0.033
HLM stability:   0.072
?
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):  4.294 Half-life (T1/2):  3.048

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.334
Human Hepatotoxicity (H-HT):  0.566 Drug-induced Liver Injury (DILI):  0.253
AMES Toxicity:  0.775 Rat Oral Acute Toxicity:  0.913
Maximum Recommended Daily Dose:  0.972 Skin Sensitization:  0.944
Carcinogencity:  0.296 Eye Corrosion:  0.0
Eye Irritation:  0.109 Respiratory Toxicity:  0.978
Drug-induced Neurotoxicity:  0.206 Ototoxicity:  0.885
Hematotoxicity:  0.412 Drug-induced Nephrotoxicity:  0.67
Genotoxicity:  0.987 RPMI-8226 Immunitoxicity:  0.392
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.23
BCF:   1.568
?
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:   3.882
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.335
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.745
?
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
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[25590529]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28626 Isodon rubescens 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

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 NPC236716 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
1.0 High Similarity NPC94141
1.0 High Similarity NPC320451
0.7586 Intermediate Similarity NPC157929
0.6615 Remote Similarity NPC229752
0.6212 Remote Similarity NPC107385
0.5938 Remote Similarity NPC17165
0.5692 Remote Similarity NPC63244
0.5692 Remote Similarity NPC122339
0.5522 Remote Similarity NPC471244
0.5429 Remote Similarity NPC78836
0.5303 Remote Similarity NPC471247
0.5286 Remote Similarity NPC471245

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC236716 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