Natural Product: NPC56413

Natural Product IDNPC56413
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sculponeatin N
IUPAC Name n.a.
Synonyms Sculponeatin N
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2022475
PubChem CID 49870969
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 CRJKTSIXXJOHPU-PULXTJHUSA-N
Standard InCHI InChI=1S/C20H28O4/c1-12-13-5-6-14-19(8-4-7-18(2,3)15(19)10-21)11-24-17(23)20(14,9-13)16(12)22/h13-15,21H,1,4-11H2,2-3H3/t13-,14+,15-,19-,20+/m1/s1
SMILES C=C1[C@@H]2CC[C@H]3[C@@]4(CCCC(C)(C)[C@H]4CO)COC(=O)[C@]3(C2)C1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.2 Volume:   347.502
?
Van der Waals volume.
Dense:   0.956 LogP:   1.691
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.857
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.242
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   63.6
?
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:   0.455 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.089 Fsp3:   0.8
MCE-18:   100.5
?
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:   0.206 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
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:   0.489 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.527 MDCK Permeability:   -5.101
Pgp-inhibitor:   0.241 Pgp-substrate:   0.023
PAMPA:   0.1
?
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):   0.001
20% Bioavailability (F20%):   0.028 30% Bioavailability (F30%):   0.135
50% Bioavailability (F50%):   0.355

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.599 MRP1:   0.357
Plasma Protein Binding (PPB):   90.651% Volume Distribution (VD):   0.249
Fu: 7.352%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.169
BSEP inhibitor:   0.639

ADMET: Metabolism

CYP1A2-inhibitor:   0.79 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.932 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.515 CYP2D6-substrate:   0.275
CYP3A4-inhibitor:   0.964 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.782
?
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):  3.99 Half-life (T1/2):  1.435

ADMET: Toxicity

hERG Blockers:  0.048 hERG Blockers (10um):  0.328
Human Hepatotoxicity (H-HT):  0.779 Drug-induced Liver Injury (DILI):  0.242
AMES Toxicity:  0.508 Rat Oral Acute Toxicity:  0.304
Maximum Recommended Daily Dose:  0.4 Skin Sensitization:  0.962
Carcinogencity:  0.85 Eye Corrosion:  0.005
Eye Irritation:  0.283 Respiratory Toxicity:  0.285
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.654
Hematotoxicity:  0.363 Drug-induced Nephrotoxicity:  0.672
Genotoxicity:  0.654 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.346
BCF:   1.64
?
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:   4.177
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.765
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.162
?
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
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. PMID[19099464]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19697926]
NPO8991 Carcinus maenas Species Carcinidae Eukaryota n.a. n.a. n.a. PMID[2421673]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota aerial parts Muli County, Sichuan Province, China 2011-AUG PMID[24219809]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. leaf n.a. PMID[9599286]
NPO17240 Crematogaster brevis Species Formicidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20336 Arctotheca calendula Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16021 Boletus bovinus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8991 Carcinus maenas Species Carcinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19889 Cereus stellatus Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17508 Danae racemosa Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20470 Elaeagnus orientalis Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20115 Melampodium argophyllum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19763 Meloidogyne incognita Species Meloidogynidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1558 Ozothamnus obcordatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20543 Psydrax livida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16409 Quercus pedunculata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21614 Urceolaria scruposa Species Trichodinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19768 Xylosalsola arbuscula Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16021 Boletus bovinus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17508 Danae racemosa Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19768 Xylosalsola arbuscula Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20336 Arctotheca calendula Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8991 Carcinus maenas Species Carcinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20470 Elaeagnus orientalis Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16409 Quercus pedunculata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1558 Ozothamnus obcordatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20543 Psydrax livida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17240 Crematogaster brevis Species Formicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20115 Melampodium argophyllum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19889 Cereus stellatus Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19763 Meloidogyne incognita Species Meloidogynidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21614 Urceolaria scruposa Species Trichodinidae 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
NPT111 Cell line K562 Homo sapiens IC50 = 210.0 nM PMID[22483090]

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 NPC56413 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
0.623 Remote Similarity NPC41649
0.5373 Remote Similarity NPC236585
0.5231 Remote Similarity NPC267921

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC56413 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