Natural Product: NPC307079

Natural Product IDNPC307079
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ORJVLIMAQARNOU-LXNAOKSISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44602428
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones
            • [CHEMONTID:0001771] Germacranolides and derivatives

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 ORJVLIMAQARNOU-LXNAOKSISA-N
Standard InCHI InChI=1S/C17H22O4/c1-10-6-5-7-11(2)9-15-16(12(3)17(19)21-15)14(8-10)20-13(4)18/h7-8,14-16H,3,5-6,9H2,1-2,4H3/b10-8+,11-7+/t14-,15?,16?/m0/s1
SMILES C/C/1=C[C@@H](C2C(=C)C(=O)OC2C/C(=C/CC1)/C)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.15 Volume:   307.454
?
Van der Waals volume.
Dense:   0.944 LogP:   2.144
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.238
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.322
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   52.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.423 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.52 Fsp3:   0.529
MCE-18:   34.462
?
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:   0.266 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.236
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.623 Promiscuous compounds:   0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.671 MDCK Permeability:   -4.61
Pgp-inhibitor:   0.968 Pgp-substrate:   0.006
PAMPA:   0.073
?
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):   0.191
20% Bioavailability (F20%):   0.365 30% Bioavailability (F30%):   0.646
50% Bioavailability (F50%):   0.74

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.856
Plasma Protein Binding (PPB):   87.939% Volume Distribution (VD):   -0.196
Fu: 10.627%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.001
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.02 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.083 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   0.967 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.939
HLM stability:   0.458
?
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):  6.551 Half-life (T1/2):  1.274

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.171
Human Hepatotoxicity (H-HT):  0.734 Drug-induced Liver Injury (DILI):  0.975
AMES Toxicity:  0.478 Rat Oral Acute Toxicity:  0.146
Maximum Recommended Daily Dose:  0.584 Skin Sensitization:  0.864
Carcinogencity:  0.627 Eye Corrosion:  0.035
Eye Irritation:  0.829 Respiratory Toxicity:  0.063
Drug-induced Neurotoxicity:  0.747 Ototoxicity:  0.316
Hematotoxicity:  0.398 Drug-induced Nephrotoxicity:  0.689
Genotoxicity:  0.709 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.036 Hek293 Cytotoxicity:  0.288
BCF:   1.299
?
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:   3.976
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.659
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.184
?
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
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. DOI[10.1080/10412905.2001.9699624]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[11912066]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[12419922]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[21188975]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[30813368]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38695450]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38851735]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29515 Laurus nobilis Species Lauraceae 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 NPC307079 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
0.925 High Similarity NPC171204
0.925 High Similarity NPC606745
0.9024 High Similarity NPC611318
0.7551 Intermediate Similarity NPC470755
0.7551 Intermediate Similarity NPC298801
0.68 Remote Similarity NPC481909
0.68 Remote Similarity NPC158756
0.68 Remote Similarity NPC601035
0.6667 Remote Similarity NPC476028
0.6522 Remote Similarity NPC97516
0.6415 Remote Similarity NPC469910
0.6364 Remote Similarity NPC481911
0.6327 Remote Similarity NPC270126
0.6087 Remote Similarity NPC58956
0.6087 Remote Similarity NPC163003
0.6087 Remote Similarity NPC295633
0.6087 Remote Similarity NPC269206
0.5882 Remote Similarity NPC50637
0.5769 Remote Similarity NPC250940
0.5769 Remote Similarity NPC169575
0.5741 Remote Similarity NPC482131
0.5686 Remote Similarity NPC609300
0.5686 Remote Similarity NPC610417
0.5636 Remote Similarity NPC482130
0.5636 Remote Similarity NPC482128
0.5636 Remote Similarity NPC482129
0.5636 Remote Similarity NPC605339
0.56 Remote Similarity NPC301477
0.56 Remote Similarity NPC25684
0.5536 Remote Similarity NPC269509
0.551 Remote Similarity NPC167881
0.551 Remote Similarity NPC98557
0.5472 Remote Similarity NPC116177
0.5472 Remote Similarity NPC165383
0.5455 Remote Similarity NPC281132
0.5455 Remote Similarity NPC482126
0.5455 Remote Similarity NPC320630
0.5455 Remote Similarity NPC266957
0.5439 Remote Similarity NPC40746
0.537 Remote Similarity NPC473390
0.537 Remote Similarity NPC194871
0.537 Remote Similarity NPC488296
0.5357 Remote Similarity NPC307411
0.5345 Remote Similarity NPC134725
0.5345 Remote Similarity NPC48657
0.5294 Remote Similarity NPC488306
0.5283 Remote Similarity NPC470256
0.5283 Remote Similarity NPC476355
0.5283 Remote Similarity NPC600792
0.5283 Remote Similarity NPC610427
0.5273 Remote Similarity NPC178702
0.5273 Remote Similarity NPC272814
0.5263 Remote Similarity NPC131669
0.5263 Remote Similarity NPC482127
0.5263 Remote Similarity NPC481806
0.5263 Remote Similarity NPC17585
0.5185 Remote Similarity NPC151770
0.5185 Remote Similarity NPC7563
0.5185 Remote Similarity NPC609663
0.5179 Remote Similarity NPC202672
0.5179 Remote Similarity NPC250315
0.5172 Remote Similarity NPC486031
0.5167 Remote Similarity NPC184463
0.5098 Remote Similarity NPC140287
0.5091 Remote Similarity NPC607063
0.5091 Remote Similarity NPC607495
0.5091 Remote Similarity NPC610688
0.5082 Remote Similarity NPC486034
0.5082 Remote Similarity NPC482132

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC307079 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