Natural Product: NPC20479

Natural Product IDNPC20479
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Inflexinol
IUPAC Name n.a.
Synonyms Inflexinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL225258
PubChem CID 44421641
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 ZMYDEPIDSFWDLQ-AZPRSEESSA-N
Standard InCHI InChI=1S/C24H34O7/c1-11-14-7-16(30-12(2)25)20-23(6)17(28)8-18(31-13(3)26)22(4,5)19(23)15(27)10-24(20,9-14)21(11)29/h14-20,27-28H,1,7-10H2,2-6H3/t14-,15+,16+,17+,18+,19-,20+,23-,24+/m1/s1
SMILES C=C1[C@@H]2C[C@@H]([C@H]3[C@]4(C)[C@H](C[C@@H](C(C)(C)[C@H]4[C@H](C[C@]3(C2)C1=O)O)OC(=O)C)O)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   434.23 Volume:   440.42
?
Van der Waals volume.
Dense:   0.986 LogP:   1.742
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.988
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.517
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   110.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.506 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.153 Fsp3:   0.792
MCE-18:   116.837
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.615 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.328 Promiscuous compounds:   0.34

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.327 MDCK Permeability:   -5.03
Pgp-inhibitor:   0.869 Pgp-substrate:   0.407
PAMPA:   0.307
?
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):   0.031
20% Bioavailability (F20%):   0.329 30% Bioavailability (F30%):   0.821
50% Bioavailability (F50%):   0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.945
Plasma Protein Binding (PPB):   48.884% Volume Distribution (VD):   -0.255
Fu: 52.257%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.021
BSEP inhibitor:   0.848

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.011
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.142
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.391
CYP3A4-inhibitor:   0.851 CYP3A4-substrate:   0.986
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.94
HLM stability:   0.727
?
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):  4.454 Half-life (T1/2):  1.921

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.115
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.563
AMES Toxicity:  0.627 Rat Oral Acute Toxicity:  0.697
Maximum Recommended Daily Dose:  0.659 Skin Sensitization:  0.922
Carcinogencity:  0.756 Eye Corrosion:  0.001
Eye Irritation:  0.084 Respiratory Toxicity:  0.418
Drug-induced Neurotoxicity:  0.11 Ototoxicity:  0.603
Hematotoxicity:  0.653 Drug-induced Nephrotoxicity:  0.785
Genotoxicity:  0.968 RPMI-8226 Immunitoxicity:  0.099
A549 Cytotoxicity:  0.207 Hek293 Cytotoxicity:  0.231
BCF:   0.509
?
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:   3.373
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.318
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.62
?
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
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[10896056]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11374970]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17338565]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21273070]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[22066578]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26913 Isodon excisus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26913 Isodon excisus 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 440.0 nM PMID[17338565]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 940.0 nM PMID[17338565]

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 NPC20479 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
0.7368 Intermediate Similarity NPC98837
0.7241 Intermediate Similarity NPC28864
0.7167 Intermediate Similarity NPC38296
0.7167 Intermediate Similarity NPC293866
0.6721 Remote Similarity NPC38471
0.6557 Remote Similarity NPC53890
0.5873 Remote Similarity NPC89099
0.5873 Remote Similarity NPC162459
0.5625 Remote Similarity NPC10864
0.5584 Remote Similarity NPC324253
0.5556 Remote Similarity NPC98639
0.5469 Remote Similarity NPC46848
0.5467 Remote Similarity NPC327093
0.5395 Remote Similarity NPC316930
0.5385 Remote Similarity NPC275990
0.5294 Remote Similarity NPC166993
0.5152 Remote Similarity NPC301787
0.5077 Remote Similarity NPC130840
0.5075 Remote Similarity NPC29410
0.5072 Remote Similarity NPC138908
0.5072 Remote Similarity NPC176949

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC20479 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