Natural Product: NPC272

Natural Product IDNPC272
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MWQRAOGWLXTMIC-TUGJPZLJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 21630005
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003422] 7,9'-epoxylignans

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 MWQRAOGWLXTMIC-TUGJPZLJSA-N
Standard InCHI InChI=1S/C20H24O7/c1-25-17-7-11(3-5-15(17)22)19(24)14-10-27-20(13(14)9-21)12-4-6-16(23)18(8-12)26-2/h3-8,13-14,19-24H,9-10H2,1-2H3/t13-,14+,19+,20+/m0/s1
SMILES COc1cc(ccc1O)[C@H]([C@@H]1CO[C@H](c2ccc(c(c2)OC)O)[C@H]1CO)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.15 Volume:   374.52
?
Van der Waals volume.
Dense:   1.004 LogP:   0.381
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.699
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.677
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   108.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.612 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.716 Fsp3:   0.4
MCE-18:   62.429
?
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:   0
Colloidal aggregators:   0.413 Fluc inhibitor:   0.338
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.143
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.163 Promiscuous compounds:   0.337

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.702 MDCK Permeability:   -5.165
Pgp-inhibitor:   0.012 Pgp-substrate:   0.316
PAMPA:   0.213
?
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):   0.054
20% Bioavailability (F20%):   0.507 30% Bioavailability (F30%):   0.849
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.879
Plasma Protein Binding (PPB):   75.296% Volume Distribution (VD):   0.053
Fu: 26.312%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.621
BSEP inhibitor:   0.034

ADMET: Metabolism

CYP1A2-inhibitor:   0.015 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.092
CYP2C9-inhibitor:   0.302 CYP2C9-substrate:   0.029
CYP2D6-inhibitor:   0.758 CYP2D6-substrate:   0.185
CYP3A4-inhibitor:   0.921 CYP3A4-substrate:   0.588
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.924
HLM stability:   0.41
?
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):  9.19 Half-life (T1/2):  2.13

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.377
Human Hepatotoxicity (H-HT):  0.799 Drug-induced Liver Injury (DILI):  0.608
AMES Toxicity:  0.613 Rat Oral Acute Toxicity:  0.153
Maximum Recommended Daily Dose:  0.308 Skin Sensitization:  0.956
Carcinogencity:  0.351 Eye Corrosion:  0.002
Eye Irritation:  0.872 Respiratory Toxicity:  0.498
Drug-induced Neurotoxicity:  0.338 Ototoxicity:  0.733
Hematotoxicity:  0.155 Drug-induced Nephrotoxicity:  0.688
Genotoxicity:  0.835 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.518 Hek293 Cytotoxicity:  0.495
BCF:   0.486
?
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:   2.761
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.847
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.165
?
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
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[12217376]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota wood n.a. n.a. PMID[12444707]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota wood Yunnang Province, China 2000-OCT PMID[21138310]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. xylem n.a. PMID[21138310]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14834 Trachelospermum asiaticum Species Apocynaceae 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
NPT28833 No target No relevant target n.a. IC50 = 41200.0 nM PMID[36469853]
NPT1190 Organism Salmonella enterica Salmonella enterica MIC = 250.0 ug.mL-1 PMID[36469853]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 62.5 ug.mL-1 PMID[36469853]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 500.0 ug.mL-1 PMID[36469853]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 500.0 ug.mL-1 PMID[36469853]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 15.6 ug.mL-1 PMID[36469853]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 125.0 ug.mL-1 PMID[36469853]
NPT1242 Organism Salmonella typhi Salmonella enterica subsp. enterica serovar Typhi MIC = 31.3 ug.mL-1 PMID[36469853]

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 NPC272 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 NPC77040
1.0 High Similarity NPC485398
0.7759 Intermediate Similarity NPC287745
0.6852 Remote Similarity NPC478955
0.6852 Remote Similarity NPC478700
0.6364 Remote Similarity NPC473451
0.6271 Remote Similarity NPC187998
0.6271 Remote Similarity NPC257582
0.6271 Remote Similarity NPC241522
0.6154 Remote Similarity NPC115207
0.6154 Remote Similarity NPC158079
0.6154 Remote Similarity NPC228346
0.6154 Remote Similarity NPC242807
0.6154 Remote Similarity NPC40432
0.6154 Remote Similarity NPC161557
0.6154 Remote Similarity NPC153739
0.6066 Remote Similarity NPC282833
0.5882 Remote Similarity NPC476343
0.5714 Remote Similarity NPC126409
0.5714 Remote Similarity NPC99572
0.5672 Remote Similarity NPC470097
0.5625 Remote Similarity NPC42300
0.5556 Remote Similarity NPC486558
0.5424 Remote Similarity NPC27843
0.5424 Remote Similarity NPC7171
0.541 Remote Similarity NPC475875
0.5303 Remote Similarity NPC64201
0.5263 Remote Similarity NPC469480
0.5246 Remote Similarity NPC223185
0.5246 Remote Similarity NPC610778
0.5224 Remote Similarity NPC470098
0.5224 Remote Similarity NPC473266
0.5185 Remote Similarity NPC282703
0.5185 Remote Similarity NPC184733
0.5185 Remote Similarity NPC128208
0.5185 Remote Similarity NPC129570
0.5185 Remote Similarity NPC63238
0.5185 Remote Similarity NPC602603
0.5161 Remote Similarity NPC181049
0.5156 Remote Similarity NPC277804
0.5139 Remote Similarity NPC114119
0.5139 Remote Similarity NPC471415
0.5091 Remote Similarity NPC195292
0.5079 Remote Similarity NPC471942
0.5077 Remote Similarity NPC100675
0.5077 Remote Similarity NPC101624
0.5077 Remote Similarity NPC184938
0.5077 Remote Similarity NPC601691

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC272 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