Natural Product: NPC70685

Natural Product IDNPC70685
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Warburganal
IUPAC Name (1S,4aS,8aS)-1-hydroxy-5,5,8a-trimethyl-4a,6,7,8-tetrahydro-4H-naphthalene-1,2-dicarbaldehyde
Synonyms Warburganal
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL452492
PubChem CID 72502
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001670] Tertiary alcohols

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 QGMWDUUHVVLHNP-AEGPPILISA-N
Standard InCHI InChI=1S/C15H22O3/c1-13(2)7-4-8-14(3)12(13)6-5-11(9-16)15(14,18)10-17/h5,9-10,12,18H,4,6-8H2,1-3H3/t12-,14-,15+/m0/s1
SMILES O=CC1=CC[C@@H]2[C@]([C@@]1(O)C=O)(C)CCCC2(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   250.16 Volume:   269.345
?
Van der Waals volume.
Dense:   0.929 LogP:   2.905
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.975
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.746
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   13.0
TPSA:   54.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.765 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.359 Fsp3:   0.733
MCE-18:   44.462
?
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:   0.096 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.046
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.909 Promiscuous compounds:   0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.575 MDCK Permeability:   -4.64
Pgp-inhibitor:   0.119 Pgp-substrate:   0.035
PAMPA:   0.744
?
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):   0.044
20% Bioavailability (F20%):   0.197 30% Bioavailability (F30%):   0.273
50% Bioavailability (F50%):   0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.423 MRP1:   0.179
Plasma Protein Binding (PPB):   85.398% Volume Distribution (VD):   0.449
Fu: 15.669%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.934 BCRP inhibitor:   0.231
BSEP inhibitor:   0.694

ADMET: Metabolism

CYP1A2-inhibitor:   0.113 CYP1A2-substrate:   0.708
CYP2C19-inhibitor:   0.659 CYP2C19-substrate:   0.528
CYP2C9-inhibitor:   0.121 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.383 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.662 CYP3A4-substrate:   0.04
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.508
HLM stability:   0.94
?
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):  4.618 Half-life (T1/2):  1.591

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.215
Human Hepatotoxicity (H-HT):  0.54 Drug-induced Liver Injury (DILI):  0.124
AMES Toxicity:  0.673 Rat Oral Acute Toxicity:  0.537
Maximum Recommended Daily Dose:  0.565 Skin Sensitization:  0.94
Carcinogencity:  0.963 Eye Corrosion:  0.808
Eye Irritation:  0.964 Respiratory Toxicity:  0.74
Drug-induced Neurotoxicity:  0.356 Ototoxicity:  0.193
Hematotoxicity:  0.327 Drug-induced Nephrotoxicity:  0.791
Genotoxicity:  0.975 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.362
BCF:   1.981
?
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:   4.85
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.636
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.121
?
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
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[10993146]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. Tsukuba, Japan 1998-JUN PMID[12381108]
NPO19593 Placida dendritica Species Limapontiidae Eukaryota n.a. n.a. n.a. PMID[14575447]
NPO19593 Placida dendritica Species Limapontiidae Eukaryota n.a. Mediterranean n.a. PMID[14575447]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. leaf n.a. PMID[24197199]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[24254087]
NPO23467 Lobaria scrobiculata Species Lobariaceae Eukaryota n.a. n.a. n.a. PMID[24725159]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. PMID[31861466]
NPO5929 Neoscopelus microchir Species Neoscopelidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4929 Pyropia perforata Species Bangiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17965 Helenium arizonicum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22984 Aframomum sceptrum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19593 Placida dendritica Species Limapontiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30896 Polygonum hydropiper Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30896 Polygonum hydropiper Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30896 Polygonum hydropiper Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[Nippon Kogaku Zasshi, 91, (1970), 762]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17965 Helenium arizonicum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30896 Polygonum hydropiper Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23467 Lobaria scrobiculata Species Lobariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5929 Neoscopelus microchir Species Neoscopelidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19593 Placida dendritica Species Limapontiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19652 Pittosporum phillyraeoides Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4929 Pyropia perforata Species Bangiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17965 Helenium arizonicum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14437 Rimularia gibbosa Species Trapeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22984 Aframomum sceptrum Species Zingiberaceae 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
NPT91 Cell line KB Homo sapiens Activity = 0.01 ug ml-1 DOI[10.1021/np50019a002]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC > 100.0 ug.mL-1 PMID[8254349]
NPT21 Organism Aspergillus niger Aspergillus niger MIC = 50.0 ug.mL-1 PMID[8254349]
NPT771 Organism Penicillium crustosum Penicillium crustosum MIC = 50.0 ug.mL-1 PMID[8254349]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 10.0 ppm DOI[10.1021/np50019a002]
NPT2780 Organism Locusta migratoria Locusta migratoria Activity = 85.0 % DOI[10.1021/np50019a002]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 100.0 ug.mL-1 PMID[8254349]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 3.13 ug.mL-1 PMID[8254349]
NPT767 Organism Pichia jadinii Cyberlindnera jadinii MIC = 3.13 ug.mL-1 PMID[8254349]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 12.5 ug ml-1 DOI[10.1021/np50019a002]
NPT767 Organism Pichia jadinii Cyberlindnera jadinii Activity = 3.1 ug ml-1 DOI[10.1021/np50019a002]
NPT3775 Organism Biomphalaria pfeifferi Biomphalaria pfeifferi Activity = 5.0 ppm DOI[10.1021/np50019a002]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[8254349]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[8254349]
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC > 100.0 ug.mL-1 PMID[8254349]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 100.0 ug.mL-1 PMID[8254349]
NPT765 Organism Schizosaccharomyces pombe Schizosaccharomyces pombe MIC = 12.5 ug.mL-1 PMID[8254349]
NPT769 Organism Mucor mucedo Mucor mucedo MIC = 25.0 ug.mL-1 PMID[8254349]
NPT770 Organism Rhizopus microsporus var. chinensis Rhizopus microsporus var. chinensis MIC = 100.0 ug.mL-1 PMID[8254349]
NPT772 Organism Pichia anomala Wickerhamomyces anomalus MIC = 12.5 ug.mL-1 PMID[8254349]
NPT1191 Organism Spodoptera exempta Spodoptera exempta Activity = 0.1 ppm DOI[10.1021/np50019a002]
NPT3772 Organism Schistocerca gregaria Schistocerca gregaria Activity = 85.0 % DOI[10.1021/np50019a002]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Activity = 50.0 ug ml-1 DOI[10.1021/np50019a002]
NPT769 Organism Mucor mucedo Mucor mucedo Activity = 100.0 ug ml-1 DOI[10.1021/np50019a002]
NPT3776 Organism Lymnaea natalensis Radix natalensis Activity = 10.0 ppm DOI[10.1021/np50019a002]
NPT768 Organism Sclerotinia Sclerotinia MIC = 3.13 ug.mL-1 PMID[8254349]
NPT3469 Organism Biomphalaria glabrata Biomphalaria glabrata Activity = 5.0 ppm DOI[10.1021/np50019a002]

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
- Mus musculus LD50 = 20.4 mg.kg-1 DOI[10.1021/np50019a002]

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 NPC70685 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
0.5682 Remote Similarity NPC172101
0.5208 Remote Similarity NPC174314

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC70685 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