Natural Product: NPC487284

Natural Product IDNPC487284
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VUZUKTHJOMFUTI-TZPHJZDLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 118711159
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003487] Cyclic ketones
              • [CHEMONTID:0004325] Cyclohexenones

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 VUZUKTHJOMFUTI-TZPHJZDLSA-N
Standard InCHI InChI=1S/C22H32O5/c1-13-5-6-16-20(2,12-24)7-4-8-21(16,3)15(13)10-22-17(25)9-14(11-23)18(26)19(22)27-22/h9,15-16,18-19,23-24,26H,1,4-8,10-12H2,2-3H3/t15-,16-,18-,19-,20-,21+,22+/m0/s1
SMILES C=C1CC[C@H]2[C@@](C)(CCC[C@]2(C)[C@H]1C[C@@]12C(=O)C=C(CO)[C@@H]([C@@H]1O2)O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.22 Volume:   390.884
?
Van der Waals volume.
Dense:   0.962 LogP:   2.269
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.501
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.625
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   90.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.517 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.148 Fsp3:   0.773
MCE-18:   73.231
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.195 Fluc inhibitor:   0.031
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.02
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.171 Promiscuous compounds:   0.442

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.684 MDCK Permeability:   -4.647
Pgp-inhibitor:   0.007 Pgp-substrate:   0.003
PAMPA:   0.706
?
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):   0.001
20% Bioavailability (F20%):   0.084 30% Bioavailability (F30%):   0.405
50% Bioavailability (F50%):   0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.478 MRP1:   0.124
Plasma Protein Binding (PPB):   71.042% Volume Distribution (VD):   0.001
Fu: 28.106%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.628
BSEP inhibitor:   0.582

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.361 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.14
CYP2D6-inhibitor:   0.927 CYP2D6-substrate:   0.033
CYP3A4-inhibitor:   0.981 CYP3A4-substrate:   0.97
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.329
HLM stability:   0.216
?
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):  7.148 Half-life (T1/2):  1.652

ADMET: Toxicity

hERG Blockers:  0.094 hERG Blockers (10um):  0.336
Human Hepatotoxicity (H-HT):  0.623 Drug-induced Liver Injury (DILI):  0.483
AMES Toxicity:  0.691 Rat Oral Acute Toxicity:  0.262
Maximum Recommended Daily Dose:  0.44 Skin Sensitization:  0.98
Carcinogencity:  0.761 Eye Corrosion:  0.001
Eye Irritation:  0.335 Respiratory Toxicity:  0.542
Drug-induced Neurotoxicity:  0.554 Ototoxicity:  0.583
Hematotoxicity:  0.402 Drug-induced Nephrotoxicity:  0.665
Genotoxicity:  0.691 RPMI-8226 Immunitoxicity:  0.158
A549 Cytotoxicity:  0.072 Hek293 Cytotoxicity:  0.451
BCF:   1.069
?
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:   3.752
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.554
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.64
?
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
NPO40209 Myrothecium sp. SC0265 Strain Stachybotryaceae Eukaryota n.a. n.a. n.a. PMID[25089733]
NPO40209 Myrothecium sp. SC0265 Strain Stachybotryaceae 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
NPT81 Cell line A549 Homo sapiens IC50 = 39800.0 nM PMID[25089733]
NPT165 Cell line HeLa Homo sapiens IC50 = 29300.0 nM PMID[25089733]
NPT65 Cell line HepG2 Homo sapiens IC50 = 48500.0 nM PMID[25089733]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[25089733]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 100.0 ug.mL-1 PMID[25089733]

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 NPC487284 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 NPC487285
0.8621 High Similarity NPC87335
0.7812 Intermediate Similarity NPC487286
0.7812 Intermediate Similarity NPC487287
0.7705 Intermediate Similarity NPC607567
0.7031 Intermediate Similarity NPC487283
0.597 Remote Similarity NPC131366
0.5616 Remote Similarity NPC608618
0.5467 Remote Similarity NPC601221
0.5429 Remote Similarity NPC607574
0.5254 Remote Similarity NPC481631
0.5077 Remote Similarity NPC106416
0.5077 Remote Similarity NPC86316
0.5077 Remote Similarity NPC476601
0.5077 Remote Similarity NPC609165

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487284 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