Natural Product: NPC99760

Natural Product IDNPC99760
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PDDUOBCTLLRRFF-AWKHGQQRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3752158
PubChem CID 50905842
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003487] Cyclic ketones
              • [CHEMONTID:0004325] Cyclohexenones

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 PDDUOBCTLLRRFF-AWKHGQQRSA-N
Standard InCHI InChI=1S/C17H22O4/c1-9(2)10-4-5-16(3)12(10)6-11-14(21-16)13-7-17(19,8-20-13)15(11)18/h10,12-13,19H,1,4-8H2,2-3H3/t10-,12-,13-,16+,17+/m0/s1
SMILES C=C(C)[C@@H]1CC[C@]2(C)[C@H]1CC1=C([C@@H]3C[C@@](CO3)(C1=O)O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.15 Volume:   295.614
?
Van der Waals volume.
Dense:   0.982 LogP:   2.464
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.556
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.401
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.752 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.763 Fsp3:   0.706
MCE-18:   67.241
?
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:   0.094 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.01
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.559 Promiscuous compounds:   0.628

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.732 MDCK Permeability:   -4.448
Pgp-inhibitor:   0.117 Pgp-substrate:   0.671
PAMPA:   0.756
?
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):   0.0
20% Bioavailability (F20%):   0.056 30% Bioavailability (F30%):   0.161
50% Bioavailability (F50%):   0.882

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.882
Plasma Protein Binding (PPB):   88.204% Volume Distribution (VD):   0.62
Fu: 12.236%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.953 BCRP inhibitor:   0.349
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.19 CYP1A2-substrate:   0.088
CYP2C19-inhibitor:   0.509 CYP2C19-substrate:   0.074
CYP2C9-inhibitor:   0.19 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.058
CYP3A4-inhibitor:   0.029 CYP3A4-substrate:   0.016
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.416
HLM stability:   0.711
?
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):  5.962 Half-life (T1/2):  1.435

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.199
Human Hepatotoxicity (H-HT):  0.913 Drug-induced Liver Injury (DILI):  0.39
AMES Toxicity:  0.902 Rat Oral Acute Toxicity:  0.859
Maximum Recommended Daily Dose:  0.815 Skin Sensitization:  0.968
Carcinogencity:  0.978 Eye Corrosion:  0.002
Eye Irritation:  0.57 Respiratory Toxicity:  0.468
Drug-induced Neurotoxicity:  0.559 Ototoxicity:  0.373
Hematotoxicity:  0.51 Drug-induced Nephrotoxicity:  0.734
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.166
A549 Cytotoxicity:  0.348 Hek293 Cytotoxicity:  0.507
BCF:   1.395
?
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:   3.823
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.618
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.868
?
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
NPO17605 Adenaria floribunda Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[15043429]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22209460]
NPO4617 Tanacetum cinerariifolium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24253739]
NPO40151 Guignardia sp. Species Phyllostictaceae Eukaryota n.a. n.a. n.a. PMID[26577190]
NPO17605 Adenaria floribunda Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29077 Marsupella emarginata Species Gymnomitriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29186 Nardosmia laevigata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29328 Genista tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29197 Mimosa hostilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28860 Saprosma scortechinii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29527 Stemonoporus affinis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12447 Plagiochila yokogurensis Species Plagiochilaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4617 Tanacetum cinerariifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28580 Tetragonia tetragonioides Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40151 Guignardia sp. Species Phyllostictaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29342 Astraeus hygrometricus Species Astraeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29328 Genista tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4617 Tanacetum cinerariifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28860 Saprosma scortechinii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29328 Genista tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29527 Stemonoporus affinis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29291 Diplopappus fruticosus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO29122 Scyphiphora hydrophyllacea Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29186 Nardosmia laevigata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22440 Arctanthemum arcticum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29342 Astraeus hygrometricus Species Astraeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29197 Mimosa hostilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29077 Marsupella emarginata Species Gymnomitriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12447 Plagiochila yokogurensis Species Plagiochilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29448 Centaurea thessala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28860 Saprosma scortechinii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4617 Tanacetum cinerariifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17605 Adenaria floribunda Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29328 Genista tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28580 Tetragonia tetragonioides Species Aizoaceae 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
NPT20 Organism Candida albicans Candida albicans MIC=>80 > 200.0 ug ml-1 PMID[26577190]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 100.0 ug.mL-1 PMID[26577190]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[26577190]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[26577190]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 25.5 ug.mL-1 PMID[26577190]

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 NPC99760 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
0.82 Intermediate Similarity NPC101018
0.7736 Intermediate Similarity NPC482798
0.7736 Intermediate Similarity NPC482797
0.7091 Intermediate Similarity NPC482793
0.6667 Remote Similarity NPC482794
0.6429 Remote Similarity NPC611467
0.5167 Remote Similarity NPC482790

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99760 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