Natural Product: NPC211014

Natural Product IDNPC211014
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SZMVUVJWZJONPP-KIPYVINTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23955874
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 SZMVUVJWZJONPP-KIPYVINTSA-N
Standard InCHI InChI=1S/C21H20O8/c1-10-17(23)19(25)20(26)21(28-10)29-13-6-7-14-16(8-13)27-9-15(18(14)24)11-2-4-12(22)5-3-11/h2-10,17,19-23,25-26H,1H3/t10-,17-,19+,20+,21-/m0/s1
SMILES C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)Oc1ccc2c(c1)occ(c1ccc(cc1)O)c2=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.12 Volume:   386.776
?
Van der Waals volume.
Dense:   1.034 LogP:   1.213
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.539
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.294
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   129.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.519 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.654 Fsp3:   0.286
MCE-18:   80.889
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.544 Fluc inhibitor:   0.601
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.94
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.583
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.271 Promiscuous compounds:   0.315

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.012 MDCK Permeability:   -5.123
Pgp-inhibitor:   0.0 Pgp-substrate:   0.353
PAMPA:   0.998
?
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):   0.447
20% Bioavailability (F20%):   0.569 30% Bioavailability (F30%):   0.927
50% Bioavailability (F50%):   0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.246
Plasma Protein Binding (PPB):   83.663% Volume Distribution (VD):   -0.141
Fu: 17.473%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.129
BSEP inhibitor:   0.067

ADMET: Metabolism

CYP1A2-inhibitor:   0.876 CYP1A2-substrate:   0.842
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.353
CYP2C9-inhibitor:   0.59 CYP2C9-substrate:   0.902
CYP2D6-inhibitor:   0.769 CYP2D6-substrate:   0.116
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.001
?
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):  2.869 Half-life (T1/2):  3.544

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.43
Human Hepatotoxicity (H-HT):  0.586 Drug-induced Liver Injury (DILI):  0.926
AMES Toxicity:  0.804 Rat Oral Acute Toxicity:  0.217
Maximum Recommended Daily Dose:  0.212 Skin Sensitization:  0.824
Carcinogencity:  0.206 Eye Corrosion:  0.0
Eye Irritation:  0.747 Respiratory Toxicity:  0.186
Drug-induced Neurotoxicity:  0.138 Ototoxicity:  0.76
Hematotoxicity:  0.214 Drug-induced Nephrotoxicity:  0.678
Genotoxicity:  0.758 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.515 Hek293 Cytotoxicity:  0.512
BCF:   0.964
?
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:   3.651
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.65
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.283
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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
NPO40231 Streptomyces sp. RB1 Strain Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[28006913]
NPO40231 Streptomyces sp. RB1 Strain Streptomycetaceae Bacteria 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
NPT857 Cell line LLC-PK1 Sus scrofa Activity > 80.0 % PMID[28006913]
NPT1173 Organism Candida albicans SC5314 Candida albicans SC5314 MIC > 100.0 ug.mL-1 PMID[28006913]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC > 100.0 ug.mL-1 PMID[28006913]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[28006913]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[28006913]

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 NPC211014 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
0.8507 High Similarity NPC25547
0.8429 Intermediate Similarity NPC161749
0.7778 Intermediate Similarity NPC259070
0.7534 Intermediate Similarity NPC348541
0.6933 Remote Similarity NPC45165
0.6711 Remote Similarity NPC160515
0.6625 Remote Similarity NPC229729
0.6567 Remote Similarity NPC181124
0.6538 Remote Similarity NPC105511
0.6364 Remote Similarity NPC487214
0.6329 Remote Similarity NPC197896
0.6329 Remote Similarity NPC258035
0.6329 Remote Similarity NPC313163
0.6279 Remote Similarity NPC303913
0.6222 Remote Similarity NPC231194
0.622 Remote Similarity NPC601607
0.6173 Remote Similarity NPC100720
0.6 Remote Similarity NPC51326
0.5976 Remote Similarity NPC205076
0.593 Remote Similarity NPC487212
0.5679 Remote Similarity NPC135345
0.5638 Remote Similarity NPC235575
0.5556 Remote Similarity NPC479405
0.5495 Remote Similarity NPC479404
0.5488 Remote Similarity NPC331652
0.5476 Remote Similarity NPC73511
0.5465 Remote Similarity NPC43761
0.5357 Remote Similarity NPC156457
0.5352 Remote Similarity NPC605229
0.5287 Remote Similarity NPC610187
0.5278 Remote Similarity NPC479067
0.5238 Remote Similarity NPC249281
0.5238 Remote Similarity NPC108831
0.5238 Remote Similarity NPC182634
0.5176 Remote Similarity NPC603782
0.5172 Remote Similarity NPC80140
0.5169 Remote Similarity NPC479407
0.5143 Remote Similarity NPC182428
0.5116 Remote Similarity NPC46420
0.5056 Remote Similarity NPC479406
0.5054 Remote Similarity NPC475155

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC211014 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
0.8429 Intermediate Similarity NPD4381 Clinical (unspecified phase)
0.5875 Remote Similarity NPD3818 Discontinued
0.5278 Remote Similarity NPD2796 Phase 2

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