Natural Product: NPC88022

Natural Product IDNPC88022
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IMVRWUJCOBUHCO-TVKJYDDYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44583907
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic 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 IMVRWUJCOBUHCO-TVKJYDDYSA-N
Standard InCHI InChI=1S/C15H16O9/c16-5-10-12(19)13(20)14(21)15(24-10)23-6-3-8(18)11-7(17)1-2-22-9(11)4-6/h1-4,10,12-16,18-21H,5H2/t10-,12-,13+,14-,15-/m1/s1
SMILES c1coc2cc(cc(c2c1=O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.08 Volume:   308.257
?
Van der Waals volume.
Dense:   1.103 LogP:   -0.712
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.283
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.757
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   149.82
?
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:   0.458 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.866 Fsp3:   0.4
MCE-18:   66.048
?
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:   0.612 Fluc inhibitor:   0.087
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.323
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.342
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.317

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.292 MDCK Permeability:   -5.138
Pgp-inhibitor:   0.001 Pgp-substrate:   0.607
PAMPA:   0.972
?
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):   0.839
20% Bioavailability (F20%):   0.2 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.174
Plasma Protein Binding (PPB):   66.88% Volume Distribution (VD):   -0.362
Fu: 33.715%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.516
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.013
HLM stability:   0.027
?
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):  2.816 Half-life (T1/2):  3.41

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.108
Human Hepatotoxicity (H-HT):  0.687 Drug-induced Liver Injury (DILI):  0.976
AMES Toxicity:  0.936 Rat Oral Acute Toxicity:  0.072
Maximum Recommended Daily Dose:  0.065 Skin Sensitization:  0.965
Carcinogencity:  0.428 Eye Corrosion:  0.0
Eye Irritation:  0.415 Respiratory Toxicity:  0.064
Drug-induced Neurotoxicity:  0.011 Ototoxicity:  0.887
Hematotoxicity:  0.354 Drug-induced Nephrotoxicity:  0.775
Genotoxicity:  0.869 RPMI-8226 Immunitoxicity:  0.134
A549 Cytotoxicity:  0.249 Hek293 Cytotoxicity:  0.243
BCF:   0.277
?
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:   2.731
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.212
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.299
?
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
NPO33204 acer mono Species Sapindaceae Eukaryota leaves n.a. n.a. PMID[15679328]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. PMID[21377852]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24093 Drynaria fortunei Species Polypodiaceae 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

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 NPC88022 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
0.7121 Intermediate Similarity NPC191154
0.7015 Intermediate Similarity NPC134819
0.6667 Remote Similarity NPC261866
0.6575 Remote Similarity NPC197896
0.6575 Remote Similarity NPC313163
0.6575 Remote Similarity NPC234739
0.6438 Remote Similarity NPC39360
0.6438 Remote Similarity NPC29763
0.6438 Remote Similarity NPC210003
0.6351 Remote Similarity NPC95090
0.6351 Remote Similarity NPC27408
0.6351 Remote Similarity NPC189142
0.6351 Remote Similarity NPC77660
0.6316 Remote Similarity NPC80140
0.6267 Remote Similarity NPC73511
0.6184 Remote Similarity NPC60966
0.6026 Remote Similarity NPC22832
0.6026 Remote Similarity NPC243930
0.6026 Remote Similarity NPC601144
0.6 Remote Similarity NPC289667
0.5949 Remote Similarity NPC311830
0.5921 Remote Similarity NPC297987
0.5921 Remote Similarity NPC277205
0.5921 Remote Similarity NPC37919
0.5921 Remote Similarity NPC136042
0.5921 Remote Similarity NPC323593
0.5921 Remote Similarity NPC203500
0.5844 Remote Similarity NPC84362
0.575 Remote Similarity NPC607707
0.5696 Remote Similarity NPC307938
0.5696 Remote Similarity NPC285197
0.5641 Remote Similarity NPC22195
0.5641 Remote Similarity NPC21190
0.5556 Remote Similarity NPC116458
0.5556 Remote Similarity NPC246943
0.5556 Remote Similarity NPC605784
0.5529 Remote Similarity NPC479405
0.5479 Remote Similarity NPC78697
0.5465 Remote Similarity NPC479404
0.5455 Remote Similarity NPC160515
0.5432 Remote Similarity NPC486578
0.5385 Remote Similarity NPC348541
0.5357 Remote Similarity NPC251417
0.5341 Remote Similarity NPC479403
0.5316 Remote Similarity NPC161749
0.5301 Remote Similarity NPC267254
0.5301 Remote Similarity NPC601586
0.5256 Remote Similarity NPC473043
0.5256 Remote Similarity NPC331652
0.525 Remote Similarity NPC600680
0.519 Remote Similarity NPC44558
0.519 Remote Similarity NPC19709
0.519 Remote Similarity NPC143851
0.5185 Remote Similarity NPC138540
0.5128 Remote Similarity NPC93099
0.5125 Remote Similarity NPC156457
0.5122 Remote Similarity NPC224462
0.5122 Remote Similarity NPC479402
0.507 Remote Similarity NPC103409
0.5067 Remote Similarity NPC94777
0.5063 Remote Similarity NPC45165
0.5062 Remote Similarity NPC181712
0.506 Remote Similarity NPC229729
0.5057 Remote Similarity NPC275454
0.5056 Remote Similarity NPC64425

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC88022 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
0.5316 Remote Similarity NPD4381 Clinical (unspecified phase)

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