Natural Product: NPC61071

Natural Product IDNPC61071
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Enemin
IUPAC Name n.a.
Synonyms Enemin; Enmein
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL453801
PubChem CID 352542
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 MQOJPNKACWKUGI-CDKPERABSA-N
Standard InCHI InChI=1S/C20H26O6/c1-9-10-4-5-11-19(7-10,15(9)22)17(24)26-13-6-12(21)18(2,3)14-16(23)25-8-20(11,13)14/h10-14,16,21,23H,1,4-8H2,2-3H3/t10-,11-,12+,13+,14-,16-,19+,20-/m1/s1
SMILES C=C1[C@@H]2CC[C@@H]3[C@@](C2)(C1=O)C(=O)O[C@H]1C[C@@H](C(C)(C)[C@H]2[C@H](O)OC[C@@]312)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   356.526
?
Van der Waals volume.
Dense:   1.016 LogP:   0.952
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.301
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.342
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   26.0
TPSA:   93.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.382 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.568 Fsp3:   0.8
MCE-18:   124.667
?
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:   0.567 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.215 Promiscuous compounds:   0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.132 MDCK Permeability:   -4.984
Pgp-inhibitor:   0.203 Pgp-substrate:   0.641
PAMPA:   0.582
?
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):   0.083
20% Bioavailability (F20%):   0.676 30% Bioavailability (F30%):   0.907
50% Bioavailability (F50%):   0.944

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.03 MRP1:   0.735
Plasma Protein Binding (PPB):   63.599% Volume Distribution (VD):   -0.047
Fu: 38.121%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.038
BSEP inhibitor:   0.868

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.449 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.007
HLM stability:   0.014
?
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):  6.018 Half-life (T1/2):  2.92

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.297
Human Hepatotoxicity (H-HT):  0.724 Drug-induced Liver Injury (DILI):  0.794
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.303
Maximum Recommended Daily Dose:  0.834 Skin Sensitization:  0.968
Carcinogencity:  0.701 Eye Corrosion:  0.0
Eye Irritation:  0.17 Respiratory Toxicity:  0.709
Drug-induced Neurotoxicity:  0.107 Ototoxicity:  0.833
Hematotoxicity:  0.464 Drug-induced Nephrotoxicity:  0.905
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.072 Hek293 Cytotoxicity:  0.198
BCF:   0.55
?
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:   3.365
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.187
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.365
?
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
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[17020288]
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]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[20949916]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota aerial parts n.a. n.a. PMID[20949916]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[22624550]
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]
NPO26123 Isodon serra Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[32993289]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. leaf n.a. PMID[9599286]
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]
NPO16021 Boletus bovinus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20336 Arctotheca calendula Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14541 Isodon oresbia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1558 Ozothamnus obcordatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28268 Enhydra fluctuans Species Mustelidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8333 Isodon trichocarpa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16019 Isodon japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26123 Isodon serra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19768 Xylosalsola arbuscula Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21614 Urceolaria scruposa Species Trichodinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16409 Quercus pedunculata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20543 Psydrax livida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31425 Lsodon oresbia n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19763 Meloidogyne incognita Species Meloidogynidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20115 Melampodium argophyllum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19475 Isodon sculponeatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20470 Elaeagnus orientalis Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17508 Danae racemosa Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17240 Crematogaster brevis Species Formicidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28268 Enhydra fluctuans Species Mustelidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16019 Isodon japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14541 Isodon oresbia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8333 Isodon trichocarpa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8333 Isodon trichocarpa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26123 Isodon serra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16019 Isodon japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14541 Isodon oresbia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28268 Enhydra fluctuans Species Mustelidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO31127 Lsodon japonica n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31425 Lsodon oresbia n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21614 Urceolaria scruposa Species Trichodinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17508 Danae racemosa Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1927 Isodon eriocalyx Species Lamiaceae 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]
NPO26123 Isodon serra Species Lamiaceae 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]
NPO16021 Boletus bovinus Species Boletaceae 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]

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 = 1620.0 nM PMID[19697926]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[19697926]
NPT65 Cell line HepG2 Homo sapiens IC50 = 2020.0 nM PMID[19697926]
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[24219809]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[24219809]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[24219809]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 40000.0 nM PMID[24219809]
NPT116 Cell line HL-60 Homo sapiens IC50 > 40000.0 nM PMID[24219809]
NPT181 Cell line Bel-7402 Homo sapiens IC50 = 14180.0 nM PMID[30921757]
NPT515 Cell line SGC-7901 Homo sapiens IC50 = 26230.0 nM PMID[30921757]
NPT116 Cell line HL-60 Homo sapiens IC50 = 19520.0 nM PMID[30921757]
NPT306 Cell line PC-3 Homo sapiens IC50 = 19350.0 nM PMID[30921757]
NPT81 Cell line A549 Homo sapiens IC50 = 12070.0 nM PMID[30921757]
NPT111 Cell line K562 Homo sapiens IC50 = 2760.0 nM PMID[30921757]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 114.6 n.a. DOI[10.1021/np50017a016]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 33.6 n.a. DOI[10.1021/np50017a016]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 103.6 n.a. DOI[10.1021/np50017a016]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 186.0 n.a. DOI[10.1021/np50017a016]
NPT21742 Cell line L02 Homo sapiens IC50 = 25470.0 nM PMID[30921757]
NPT2 Others Unspecified n.a. Ratio = 3.41 n.a. DOI[10.1021/np50017a016]
NPT2 Others Unspecified n.a. Ratio = 1.62 n.a. DOI[10.1021/np50017a016]

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 NPC61071 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 NPC483215
0.7705 Intermediate Similarity NPC483232
0.7377 Intermediate Similarity NPC483212
0.7377 Intermediate Similarity NPC101842
0.6825 Remote Similarity NPC483231
0.5882 Remote Similarity NPC96333
0.5882 Remote Similarity NPC88833
0.5882 Remote Similarity NPC483211
0.5735 Remote Similarity NPC88469
0.5493 Remote Similarity NPC124053
0.5294 Remote Similarity NPC483214
0.507 Remote Similarity NPC483209
0.507 Remote Similarity NPC483210

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC61071 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