Natural Product: NPC201249

Natural Product IDNPC201249
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZTMPDTJBTNGZJH-MIBLXWLASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 52041672
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0003002] Hydroxycinnamic acid esters
            • [CHEMONTID:0000465] Coumaric acid esters

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 ZTMPDTJBTNGZJH-MIBLXWLASA-N
Standard InCHI InChI=1S/C21H28O9/c22-11-16-18(26)19(27)20(21(29-16)28-15-4-2-1-3-14(15)24)30-17(25)10-7-12-5-8-13(23)9-6-12/h5-10,14-16,18-24,26-27H,1-4,11H2/b10-7+/t14-,15-,16+,18+,19-,20+,21+/m0/s1
SMILES C1CC[C@@H]([C@H](C1)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)OC(=O)/C=C/c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.17 Volume:   412.033
?
Van der Waals volume.
Dense:   1.029 LogP:   0.908
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.425
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.605
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   145.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.316 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.045 Fsp3:   0.571
MCE-18:   69.667
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.761 Fluc inhibitor:   0.691
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.248
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.235
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.204 Promiscuous compounds:   0.393

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.048 MDCK Permeability:   -5.116
Pgp-inhibitor:   0.003 Pgp-substrate:   0.096
PAMPA:   0.983
?
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):   0.606
20% Bioavailability (F20%):   0.859 30% Bioavailability (F30%):   0.991
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.005
Plasma Protein Binding (PPB):   71.379% Volume Distribution (VD):   -0.291
Fu: 29.527%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.027
BSEP inhibitor:   0.087

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.284
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.034
?
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):  2.832 Half-life (T1/2):  2.051

ADMET: Toxicity

hERG Blockers:  0.054 hERG Blockers (10um):  0.214
Human Hepatotoxicity (H-HT):  0.644 Drug-induced Liver Injury (DILI):  0.706
AMES Toxicity:  0.906 Rat Oral Acute Toxicity:  0.059
Maximum Recommended Daily Dose:  0.157 Skin Sensitization:  0.999
Carcinogencity:  0.224 Eye Corrosion:  0.001
Eye Irritation:  0.533 Respiratory Toxicity:  0.054
Drug-induced Neurotoxicity:  0.147 Ototoxicity:  0.805
Hematotoxicity:  0.219 Drug-induced Nephrotoxicity:  0.526
Genotoxicity:  0.202 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.641 Hek293 Cytotoxicity:  0.647
BCF:   0.462
?
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:   3.168
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.828
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.982
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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
NPO40921 Salix glandulosa Species n.a. n.a. Twigs n.a. n.a. PMID[25098650]

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 > 10000.0 nM PMID[25098650]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 > 10000.0 nM PMID[25098650]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 15500.0 nM PMID[25098650]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[25098650]
NPT27 Others Unspecified n.a. Activity = 93.6 % PMID[25098650]

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 NPC201249 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 NPC253668
1.0 High Similarity NPC57039
1.0 High Similarity NPC83218
1.0 High Similarity NPC479471
1.0 High Similarity NPC126991
1.0 High Similarity NPC479467
1.0 High Similarity NPC479470
1.0 High Similarity NPC479472
0.6232 Remote Similarity NPC471157
0.6066 Remote Similarity NPC11724
0.5714 Remote Similarity NPC479473
0.5714 Remote Similarity NPC275721
0.5714 Remote Similarity NPC479468
0.5714 Remote Similarity NPC479474
0.561 Remote Similarity NPC487695
0.561 Remote Similarity NPC487694
0.561 Remote Similarity NPC487696
0.5556 Remote Similarity NPC472132
0.5526 Remote Similarity NPC149011
0.5287 Remote Similarity NPC487698
0.5287 Remote Similarity NPC487697
0.5246 Remote Similarity NPC224208
0.5246 Remote Similarity NPC41661
0.5217 Remote Similarity NPC52097
0.5063 Remote Similarity NPC479268

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201249 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