Natural Product: NPC49730

Natural Product IDNPC49730
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sculponeatin C
IUPAC Name n.a.
Synonyms Sculponeatin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1081517
PubChem CID 46883441
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 JWBVQJZXSQDXKU-ZYPWQORTSA-N
Standard InCHI InChI=1S/C20H24O6/c1-9-10-5-11(21)13-19(6-10,15(9)22)17(23)25-8-20(13)12-3-4-18(2)7-24-16(26-12)14(18)20/h10-14,16,21H,1,3-8H2,2H3/t10-,11-,12-,13-,14-,16+,18+,19+,20+/m1/s1
SMILES C=C1[C@@H]2C[C@H]([C@@H]3[C@@](C2)(C1=O)C(=O)OC[C@@]13[C@H]2CC[C@@]3(C)CO[C@H]([C@@H]13)O2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.16 Volume:   347.969
?
Van der Waals volume.
Dense:   1.035 LogP:   0.834
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.254
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.621
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   29.0
TPSA:   82.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.397 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.176 Fsp3:   0.8
MCE-18:   138.0
?
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:   0.628 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.169 Promiscuous compounds:   0.489

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.626 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.026 Pgp-substrate:   0.556
PAMPA:   0.787
?
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%):   0.298 30% Bioavailability (F30%):   0.15
50% Bioavailability (F50%):   0.664

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.054 MRP1:   0.277
Plasma Protein Binding (PPB):   45.493% Volume Distribution (VD):   -0.022
Fu: 57.556%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.971 BCRP inhibitor:   0.059
BSEP inhibitor:   0.942

ADMET: Metabolism

CYP1A2-inhibitor:   0.091 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.565 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.011 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.023
CYP3A4-inhibitor:   0.812 CYP3A4-substrate:   0.263
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.006
HLM stability:   0.318
?
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):  3.032 Half-life (T1/2):  2.99

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.499
Human Hepatotoxicity (H-HT):  0.777 Drug-induced Liver Injury (DILI):  0.736
AMES Toxicity:  0.88 Rat Oral Acute Toxicity:  0.771
Maximum Recommended Daily Dose:  0.844 Skin Sensitization:  0.979
Carcinogencity:  0.596 Eye Corrosion:  0.001
Eye Irritation:  0.254 Respiratory Toxicity:  0.828
Drug-induced Neurotoxicity:  0.499 Ototoxicity:  0.722
Hematotoxicity:  0.798 Drug-induced Nephrotoxicity:  0.633
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.13 Hek293 Cytotoxicity:  0.365
BCF:   0.565
?
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:   3.39
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.11
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.262
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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
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19697926]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota aerial parts Muli County, Sichuan Province, China 2011-AUG PMID[24219809]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19485 Isodon sculponeata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19485 Isodon sculponeata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19485 Isodon sculponeata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19475 Isodon sculponeatus 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
NPT111 Cell line K562 Homo sapiens IC50 = 780.0 nM PMID[19697926]
NPT81 Cell line A549 Homo sapiens IC50 = 2730.0 nM PMID[19697926]
NPT65 Cell line HepG2 Homo sapiens IC50 = 680.0 nM PMID[19697926]

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 NPC49730 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
0.8033 Intermediate Similarity NPC98069
0.8033 Intermediate Similarity NPC483216
0.7031 Intermediate Similarity NPC244247
0.6716 Remote Similarity NPC96217
0.6418 Remote Similarity NPC164600
0.6418 Remote Similarity NPC103172
0.6286 Remote Similarity NPC483251
0.6286 Remote Similarity NPC483252
0.5882 Remote Similarity NPC98633
0.5882 Remote Similarity NPC483233
0.5714 Remote Similarity NPC148279
0.5507 Remote Similarity NPC267921
0.5278 Remote Similarity NPC96333
0.5278 Remote Similarity NPC88833
0.5278 Remote Similarity NPC483211
0.5211 Remote Similarity NPC26270
0.5205 Remote Similarity NPC483234

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC49730 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