Natural Product: NPC123177

Natural Product IDNPC123177
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Linifolin A
IUPAC Name [(3aS,5R,5aR,8aR,9R,9aR)-5,8a-dimethyl-1-methylidene-2,8-dioxo-3a,4,5,5a,9,9a-hexahydroazuleno[6,5-b]furan-9-yl] acetate
Synonyms Linifolin A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL270297
PubChem CID 442272
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

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 DCNRYQODUSSOKC-JKSXDGAISA-N
Standard InCHI InChI=1S/C17H20O5/c1-8-7-12-14(9(2)16(20)22-12)15(21-10(3)18)17(4)11(8)5-6-13(17)19/h5-6,8,11-12,14-15H,2,7H2,1,3-4H3/t8-,11+,12+,14-,15-,17+/m1/s1
SMILES CC(=O)O[C@@H]1[C@H]2[C@@H](OC(=O)C2=C)C[C@H]([C@H]2[C@@]1(C)C(=O)C=C2)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.13 Volume:   307.688
?
Van der Waals volume.
Dense:   0.988 LogP:   1.184
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.402
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.754
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   69.67
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.546 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.678 Fsp3:   0.588
MCE-18:   52.889
?
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:   0.601 Fluc inhibitor:   0.019
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.065
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.55 Promiscuous compounds:   0.454

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.96 MDCK Permeability:   -4.58
Pgp-inhibitor:   0.784 Pgp-substrate:   0.335
PAMPA:   0.71
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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):   0.387
20% Bioavailability (F20%):   0.765 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.807
Plasma Protein Binding (PPB):   64.574% Volume Distribution (VD):   -0.011
Fu: 37.198%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.009
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   0.162
CYP2C19-inhibitor:   0.213 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.17 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.035
CYP3A4-inhibitor:   0.117 CYP3A4-substrate:   0.288
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.932
?
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):  5.119 Half-life (T1/2):  1.189

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.096
Human Hepatotoxicity (H-HT):  0.719 Drug-induced Liver Injury (DILI):  0.931
AMES Toxicity:  0.833 Rat Oral Acute Toxicity:  0.373
Maximum Recommended Daily Dose:  0.474 Skin Sensitization:  0.996
Carcinogencity:  0.857 Eye Corrosion:  0.612
Eye Irritation:  0.953 Respiratory Toxicity:  0.376
Drug-induced Neurotoxicity:  0.395 Ototoxicity:  0.398
Hematotoxicity:  0.807 Drug-induced Nephrotoxicity:  0.914
Genotoxicity:  0.851 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.206 Hek293 Cytotoxicity:  0.183
BCF:   0.645
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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:   3.354
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.717
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.23
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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
NPO33469 Asteraceae Family Asteraceae Eukaryota n.a. n.a. n.a. PMID[18329753]
NPO33393 pimelea sp. Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[4031900]
NPO33469 Asteraceae Family Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33393 pimelea sp. Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT168 Cell line P388 Mus musculus T/C = 107.0 % PMID[4031900]
NPT91 Cell line KB Homo sapiens ED50 = 2.0 umol/L Open TG-GATES in vivo data: Biochemistry
NPT20967 Cell line Platelet n.a. IC50 = 11440.0 nM PMID[18271521]

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 NPC123177 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 NPC70595
1.0 High Similarity NPC150978
0.8667 High Similarity NPC74103
0.8667 High Similarity NPC604741
0.8667 High Similarity NPC607377
0.8298 Intermediate Similarity NPC610944
0.8125 Intermediate Similarity NPC141191
0.7959 Intermediate Similarity NPC169205
0.6327 Remote Similarity NPC70555
0.6327 Remote Similarity NPC104961
0.6154 Remote Similarity NPC253144
0.6078 Remote Similarity NPC238593
0.6038 Remote Similarity NPC284185
0.6038 Remote Similarity NPC610110
0.5962 Remote Similarity NPC191339
0.5962 Remote Similarity NPC286341
0.58 Remote Similarity NPC21471
0.58 Remote Similarity NPC33570
0.5686 Remote Similarity NPC161957
0.566 Remote Similarity NPC70422
0.5614 Remote Similarity NPC185553
0.5472 Remote Similarity NPC193645
0.5472 Remote Similarity NPC48803
0.5472 Remote Similarity NPC275960
0.5472 Remote Similarity NPC90121
0.5472 Remote Similarity NPC610233
0.537 Remote Similarity NPC54843
0.537 Remote Similarity NPC610675
0.5357 Remote Similarity NPC604654
0.5263 Remote Similarity NPC171759
0.5185 Remote Similarity NPC289004
0.5185 Remote Similarity NPC471149
0.5088 Remote Similarity NPC203659

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC123177 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
0.5472 Remote Similarity NPD1698 Clinical (unspecified phase)

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