Natural Product: NPC123360

Natural Product IDNPC123360
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ovatodiolide
IUPAC Name n.a.
Synonyms Ovatodiolide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470287
PubChem CID 6451060
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 KTYZKXFERQUCPX-XGKXUXTPSA-N
Standard InCHI InChI=1S/C20H24O4/c1-12-5-4-6-15-11-16(23-20(15)22)9-13(2)10-18-17(8-7-12)14(3)19(21)24-18/h5,10-11,16-18H,3-4,6-9H2,1-2H3/b12-5+,13-10+/t16-,17-,18+/m1/s1
SMILES C/C/1=CCCC2=C[C@H](OC2=O)C/C(=C/[C@H]2[C@H](CC1)C(=C)C(=O)O2)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   348.149
?
Van der Waals volume.
Dense:   0.943 LogP:   2.345
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.473
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.468
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   52.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.386 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.569 Fsp3:   0.5
MCE-18:   45.6
?
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:   0.615 Fluc inhibitor:   0.194
?
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:   0.078
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.714 Promiscuous compounds:   0.173

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.788 MDCK Permeability:   -4.639
Pgp-inhibitor:   0.961 Pgp-substrate:   0.039
PAMPA:   0.058
?
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):   0.039
20% Bioavailability (F20%):   0.099 30% Bioavailability (F30%):   0.895
50% Bioavailability (F50%):   0.795

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.826
Plasma Protein Binding (PPB):   95.729% Volume Distribution (VD):   0.041
Fu: 4.89%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.002
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.021
CYP2C19-inhibitor:   0.047 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.1 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.488
CYP3A4-inhibitor:   0.11 CYP3A4-substrate:   0.307
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.984
HLM stability:   0.882
?
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):  9.101 Half-life (T1/2):  1.466

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.148
Human Hepatotoxicity (H-HT):  0.814 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.788 Rat Oral Acute Toxicity:  0.245
Maximum Recommended Daily Dose:  0.881 Skin Sensitization:  0.999
Carcinogencity:  0.784 Eye Corrosion:  0.056
Eye Irritation:  0.798 Respiratory Toxicity:  0.262
Drug-induced Neurotoxicity:  0.938 Ototoxicity:  0.368
Hematotoxicity:  0.361 Drug-induced Nephrotoxicity:  0.971
Genotoxicity:  0.792 RPMI-8226 Immunitoxicity:  0.223
A549 Cytotoxicity:  0.488 Hek293 Cytotoxicity:  0.324
BCF:   1.76
?
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:   4.402
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.118
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.664
?
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
NPO33150 Artocarpus communis Species Moraceae Eukaryota heartwood n.a. n.a. PMID[16643064]
NPO9613 Anisomeles indica Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[18547115]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. PMID[19099464]
NPO28799 Hyptis suaveolens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
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]
NPO33150 Artocarpus communis Species Moraceae Eukaryota roots Khon Kaen, Thailand 2009-DEC PMID[25537111]
NPO28799 Hyptis suaveolens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[26178912]
NPO33150 Artocarpus communis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[26178912]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. leaf n.a. PMID[9599286]
NPO28799 Hyptis suaveolens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19475 Isodon sculponeatus 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]
NPO21139 Daphniphyllum calycinum Species Daphniphyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20543 Psydrax livida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9613 Anisomeles indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1558 Ozothamnus obcordatus 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]
NPO33150 Artocarpus communis Species Moraceae 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]
NPO20115 Melampodium argophyllum Species Asteraceae 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]
NPO17240 Crematogaster brevis Species Formicidae 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]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9613 Anisomeles indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28799 Hyptis suaveolens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21482 Crotalaria laburnifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9613 Anisomeles indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28799 Hyptis suaveolens 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]
NPO28799 Hyptis suaveolens Species Lamiaceae Eukaryota 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]
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]
NPO9613 Anisomeles indica Species Lamiaceae 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]
NPO28799 Hyptis suaveolens Species Lamiaceae 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
NPT65 Cell line HepG2 Homo sapiens IC50 = 10000.0 nM PMID[18547115]
NPT81 Cell line A549 Homo sapiens IC50 = 9600.0 nM PMID[18547115]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 9500.0 nM PMID[18547115]
NPT83 Cell line MCF7 Homo sapiens IC50 = 9500.0 nM PMID[18547115]
NPT111 Cell line K562 Homo sapiens IC50 = 1250.0 nM PMID[19697926]
NPT81 Cell line A549 Homo sapiens IC50 = 1960.0 nM PMID[19697926]
NPT65 Cell line HepG2 Homo sapiens IC50 = 1400.0 nM PMID[19697926]
NPT90 Cell line DU-145 Homo sapiens IC50 = 32600.0 nM PMID[26178912]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 7400.0 nM PMID[18547115]
NPT610 Others Molecular identity unknown n.a. IC50 = 4000.0 nM PMID[26178912]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 12100.0 nM PMID[26178912]
NPT20967 Cell line Platelet n.a. IC50 > 100000.0 nM PMID[18547115]
NPT20967 Cell line Platelet n.a. IC50 = 19700.0 nM PMID[18547115]

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 NPC123360 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
0.7308 Intermediate Similarity NPC173609
0.7174 Intermediate Similarity NPC58956
0.7174 Intermediate Similarity NPC163003
0.7174 Intermediate Similarity NPC295633
0.7174 Intermediate Similarity NPC269206
0.7083 Intermediate Similarity NPC140287
0.7037 Intermediate Similarity NPC284902
0.6909 Remote Similarity NPC295312
0.6863 Remote Similarity NPC476355
0.6809 Remote Similarity NPC601805
0.6491 Remote Similarity NPC475703
0.625 Remote Similarity NPC160138
0.614 Remote Similarity NPC215364
0.6111 Remote Similarity NPC7563
0.5789 Remote Similarity NPC267231
0.5741 Remote Similarity NPC609300
0.5741 Remote Similarity NPC610417
0.5636 Remote Similarity NPC610427
0.5577 Remote Similarity NPC151648
0.5517 Remote Similarity NPC250315
0.537 Remote Similarity NPC196653
0.537 Remote Similarity NPC603669
0.5357 Remote Similarity NPC600792
0.5333 Remote Similarity NPC93763
0.5273 Remote Similarity NPC471465
0.5263 Remote Similarity NPC609663
0.5246 Remote Similarity NPC108816
0.5185 Remote Similarity NPC329852
0.5172 Remote Similarity NPC607063
0.5172 Remote Similarity NPC607495
0.5172 Remote Similarity NPC610688
0.5094 Remote Similarity NPC235906
0.5088 Remote Similarity NPC470256
0.5085 Remote Similarity NPC606027
0.5085 Remote Similarity NPC606441
0.5082 Remote Similarity NPC611012

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC123360 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