Natural Product: NPC302462

Natural Product IDNPC302462
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MWLHJCBZAWPKEY-UEHSGRLWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12966869
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 MWLHJCBZAWPKEY-UEHSGRLWSA-N
Standard InCHI InChI=1S/C20H26O5/c1-10(9-21)11-7-12-13-8-14-19(2,3)5-4-6-20(14,18(24)25-13)15(12)17(23)16(11)22/h7,10,13-14,21-23H,4-6,8-9H2,1-3H3/t10-,13-,14-,20+/m0/s1
SMILES C[C@@H](CO)c1cc2[C@@H]3C[C@H]4C(C)(C)CCC[C@@]4(c2c(c1O)O)C(=O)O3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.18 Volume:   353.656
?
Van der Waals volume.
Dense:   0.979 LogP:   2.408
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.291
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.951
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.565 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.525 Fsp3:   0.65
MCE-18:   121.091
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.375 Fluc inhibitor:   0.045
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.299
?
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:   0.094 Promiscuous compounds:   0.114

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.492 MDCK Permeability:   -4.946
Pgp-inhibitor:   0.006 Pgp-substrate:   0.091
PAMPA:   0.942
?
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%):   0.014 30% Bioavailability (F30%):   0.014
50% Bioavailability (F50%):   0.125

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.115 MRP1:   0.988
Plasma Protein Binding (PPB):   75.864% Volume Distribution (VD):   0.074
Fu: 24.175%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.409 BCRP inhibitor:   0.004
BSEP inhibitor:   0.51

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.018 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.098
CYP3A4-inhibitor:   0.201 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.008
HLM stability:   0.015
?
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):  12.404 Half-life (T1/2):  1.789

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.386
Human Hepatotoxicity (H-HT):  0.775 Drug-induced Liver Injury (DILI):  0.633
AMES Toxicity:  0.833 Rat Oral Acute Toxicity:  0.667
Maximum Recommended Daily Dose:  0.967 Skin Sensitization:  0.995
Carcinogencity:  0.922 Eye Corrosion:  0.0
Eye Irritation:  0.259 Respiratory Toxicity:  0.503
Drug-induced Neurotoxicity:  0.505 Ototoxicity:  0.626
Hematotoxicity:  0.623 Drug-induced Nephrotoxicity:  0.982
Genotoxicity:  0.918 RPMI-8226 Immunitoxicity:  0.207
A549 Cytotoxicity:  0.884 Hek293 Cytotoxicity:  0.427
BCF:   1.217
?
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:   3.894
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.488
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.805
?
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
NPO17119 Dalea versicolor Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15043439]
NPO18606 Achyrocline bogotensis Species Asteraceae Eukaryota n.a. Colombian n.a. PMID[15844937]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. root n.a. PMID[18401845]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[19775092]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota aerial parts Shangrila, Yunnan Province, China 2008-AUG PMID[21534539]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[21534539]
NPO12148.2 Acer pictum subsp. okamotoanum Subspecies Sapindaceae Eukaryota n.a. n.a. n.a. PMID[9461665]
NPO17119 Dalea versicolor Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12148.2 Acer pictum subsp. okamotoanum Subspecies Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17911 Blepharisma japonicum Species Blepharismidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18606 Achyrocline bogotensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19522 Arthropsis truncata Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13832 Aspilia hispida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15497 Caria ino Species Riodinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2377 Cetraria ciliaris Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19580 Chamaemelum fuscatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18356 Stachys tuberifera Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16990 Verbesina virgata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18435 Tylophora atrofolliculata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16997 Talaromyces aculeatus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17783 Sideritis cystosiphon Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13414 Senecio fuertesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19638 Scutellaria albida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4984 Salvia cana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4230 Protoparmeliopsis peltata Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19777 Pholiota adiposa Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17643 Penicillium pedemontanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10852 Felimare midatlantica Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16567 Doriopsilla areolata Species Dendrodorididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19311 Dasymaschalon blumei Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18435 Tylophora atrofolliculata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18356 Stachys tuberifera Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18356 Stachys tuberifera Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18435 Tylophora atrofolliculata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17362 Alstonia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18055 Isodon adenolomus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3291 Cynanchum auriculatum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17911 Blepharisma japonicum Species Blepharismidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15497 Caria ino Species Riodinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2377 Cetraria ciliaris Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13414 Senecio fuertesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19580 Chamaemelum fuscatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4984 Salvia cana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19638 Scutellaria albida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4230 Protoparmeliopsis peltata Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19522 Arthropsis truncata Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19311 Dasymaschalon blumei Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17783 Sideritis cystosiphon Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10852 Felimare midatlantica Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16997 Talaromyces aculeatus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17643 Penicillium pedemontanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16990 Verbesina virgata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18356 Stachys tuberifera Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16567 Doriopsilla areolata Species Dendrodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18435 Tylophora atrofolliculata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18606 Achyrocline bogotensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19777 Pholiota adiposa Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12148.2 Acer pictum subsp. okamotoanum Subspecies Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17119 Dalea versicolor Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13832 Aspilia hispida Species Asteraceae 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

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 NPC302462 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
1.0 High Similarity NPC474991
0.9107 High Similarity NPC487093
0.8571 High Similarity NPC84786
0.6 Remote Similarity NPC127046
0.5455 Remote Similarity NPC99795
0.5224 Remote Similarity NPC471853
0.5224 Remote Similarity NPC478653
0.5139 Remote Similarity NPC191899
0.507 Remote Similarity NPC246229
0.507 Remote Similarity NPC605250

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC302462 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