Natural Product: NPC26241

Natural Product IDNPC26241
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SMFKCIHIAHWGGL-AWOKGZDASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2349426
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001292] Cyclic alcohols and derivatives
            • [CHEMONTID:0002509] Cyclitols and derivatives
              • [CHEMONTID:0002512] Quinic acids 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 SMFKCIHIAHWGGL-AWOKGZDASA-N
Standard InCHI InChI=1S/C17H20O9/c1-25-16(23)17(24)7-12(20)15(13(21)8-17)26-14(22)5-3-9-2-4-10(18)11(19)6-9/h2-6,12-13,15,18-21,24H,7-8H2,1H3/b5-3+/t12-,13-,15-,17+/m1/s1
SMILES COC(=O)[C@]1(O)C[C@@H](O)[C@H]([C@@H](C1)O)OC(=O)/C=C/c1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.11 Volume:   348.769
?
Van der Waals volume.
Dense:   1.055 LogP:   0.964
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.31
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.284
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   153.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.267 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.606 Fsp3:   0.412
MCE-18:   59.5
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.524 Fluc inhibitor:   0.954
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.116
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.334
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.339 Promiscuous compounds:   0.509

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.075 MDCK Permeability:   -5.085
Pgp-inhibitor:   0.001 Pgp-substrate:   0.509
PAMPA:   0.99
?
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):   0.094
20% Bioavailability (F20%):   0.986 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.515
Plasma Protein Binding (PPB):   50.461% Volume Distribution (VD):   -0.1
Fu: 49.175%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.117
BSEP inhibitor:   0.108

ADMET: Metabolism

CYP1A2-inhibitor:   0.013 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.086
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.986
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.905
HLM stability:   0.143
?
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):  7.113 Half-life (T1/2):  2.093

ADMET: Toxicity

hERG Blockers:  0.066 hERG Blockers (10um):  0.255
Human Hepatotoxicity (H-HT):  0.65 Drug-induced Liver Injury (DILI):  0.369
AMES Toxicity:  0.532 Rat Oral Acute Toxicity:  0.308
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.977
Carcinogencity:  0.476 Eye Corrosion:  0.003
Eye Irritation:  0.564 Respiratory Toxicity:  0.582
Drug-induced Neurotoxicity:  0.049 Ototoxicity:  0.829
Hematotoxicity:  0.061 Drug-induced Nephrotoxicity:  0.341
Genotoxicity:  0.817 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.799 Hek293 Cytotoxicity:  0.194
BCF:   0.562
?
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:   3.226
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.838
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.184
?
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
NPO33307 pimpinella brachycarpa Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[23462643]
NPO33307 pimpinella brachycarpa Species Apiaceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 92.6 % PMID[12061875]
NPT34 Cell line BV-2 Mus musculus IC50 = 16570.0 nM PMID[23394284]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 13.02 % PMID[19921834]

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 NPC26241 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
0.8302 Intermediate Similarity NPC474875
0.8235 Intermediate Similarity NPC182217
0.74 Intermediate Similarity NPC474275
0.7368 Intermediate Similarity NPC277315
0.7368 Intermediate Similarity NPC472016
0.7368 Intermediate Similarity NPC192831
0.7308 Intermediate Similarity NPC605000
0.7222 Intermediate Similarity NPC258469
0.7222 Intermediate Similarity NPC43158
0.7222 Intermediate Similarity NPC610147
0.6897 Remote Similarity NPC295492
0.6897 Remote Similarity NPC303683
0.6897 Remote Similarity NPC274891
0.6415 Remote Similarity NPC224208
0.6415 Remote Similarity NPC41661
0.6364 Remote Similarity NPC306343
0.6346 Remote Similarity NPC233669
0.6271 Remote Similarity NPC219428
0.6269 Remote Similarity NPC93498
0.6226 Remote Similarity NPC281277
0.6111 Remote Similarity NPC309434
0.6094 Remote Similarity NPC163883
0.6042 Remote Similarity NPC226250
0.5968 Remote Similarity NPC319628
0.5818 Remote Similarity NPC147192
0.5781 Remote Similarity NPC205751
0.569 Remote Similarity NPC470849
0.5645 Remote Similarity NPC233350
0.5645 Remote Similarity NPC70680
0.5517 Remote Similarity NPC168799
0.5507 Remote Similarity NPC322660
0.5479 Remote Similarity NPC19380
0.5424 Remote Similarity NPC488563
0.5424 Remote Similarity NPC474895
0.5286 Remote Similarity NPC146277
0.5254 Remote Similarity NPC106406
0.5246 Remote Similarity NPC470848
0.5238 Remote Similarity NPC13818
0.5094 Remote Similarity NPC95381
0.5091 Remote Similarity NPC217472
0.5075 Remote Similarity NPC206095
0.5075 Remote Similarity NPC35702
0.5075 Remote Similarity NPC224389

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC26241 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