Natural Product: NPC222936

Natural Product IDNPC222936
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tricin-5-O-Glucopyranoside
IUPAC Name 7-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1224897
PubChem CID 49800176
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid 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 FLSOTPIEFVBPBU-LDBVRRDLSA-N
Standard InCHI InChI=1S/C23H24O12/c1-31-15-3-9(4-16(32-2)19(15)27)12-7-11(26)18-13(33-12)5-10(25)6-14(18)34-23-22(30)21(29)20(28)17(8-24)35-23/h3-7,17,20-25,27-30H,8H2,1-2H3/t17-,20-,21+,22-,23-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2cc(O)cc3c2c(=O)cc(o3)c2cc(OC)c(c(c2)OC)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   492.13 Volume:   456.529
?
Van der Waals volume.
Dense:   1.078 LogP:   0.916
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.34
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.992
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   188.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.272 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.99 Fsp3:   0.348
MCE-18:   89.71
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.567 Fluc inhibitor:   0.189
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.945
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.884
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.095 Promiscuous compounds:   0.652

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.121 MDCK Permeability:   -5.395
Pgp-inhibitor:   0.001 Pgp-substrate:   0.257
PAMPA:   0.43
?
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):   0.423
20% Bioavailability (F20%):   0.124 30% Bioavailability (F30%):   0.938
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.64
Plasma Protein Binding (PPB):   86.628% Volume Distribution (VD):   -0.155
Fu: 12.136%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.967
BSEP inhibitor:   0.081

ADMET: Metabolism

CYP1A2-inhibitor:   0.214 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.043 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.084 CYP2D6-substrate:   0.892
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.51
?
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):  3.055 Half-life (T1/2):  3.849

ADMET: Toxicity

hERG Blockers:  0.027 hERG Blockers (10um):  0.122
Human Hepatotoxicity (H-HT):  0.616 Drug-induced Liver Injury (DILI):  0.953
AMES Toxicity:  0.868 Rat Oral Acute Toxicity:  0.047
Maximum Recommended Daily Dose:  0.136 Skin Sensitization:  0.987
Carcinogencity:  0.554 Eye Corrosion:  0.0
Eye Irritation:  0.64 Respiratory Toxicity:  0.051
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.76
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.221
Genotoxicity:  0.806 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.278 Hek293 Cytotoxicity:  0.528
BCF:   0.374
?
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:   3.021
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.37
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.553
?
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
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11356-018-3422-z]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. PMID[15516765]
NPO30156 Sasa kurilensis Species Poaceae Eukaryota n.a. leaf n.a. PMID[18262577]
NPO33290 fargesia robusta Species Poaceae Eukaryota leaves n.a. n.a. PMID[20863141]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. PMID[20973550]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. PMID[23700450]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. leaf n.a. PMID[23849114]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. PMID[24310066]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. seed n.a. PMID[25433632]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. seed n.a. PMID[26860358]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. PMID[31861466]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. PMID[38792127]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Petiole n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Protoplast n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. seed n.a. Database[MetaboLights]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8541 Oryza sativa Species Poaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8541 Oryza sativa Species Poaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.063 n.a. PMID[20863141]
NPT35 Others n.a. n.a. Activity = 18.2 n.a. PMID[20863141]

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 NPC222936 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
0.7945 Intermediate Similarity NPC83283
0.6582 Remote Similarity NPC110349
0.642 Remote Similarity NPC610763
0.6386 Remote Similarity NPC284960
0.6296 Remote Similarity NPC609879
0.6145 Remote Similarity NPC182045
0.6145 Remote Similarity NPC325555
0.6145 Remote Similarity NPC226304
0.6145 Remote Similarity NPC599850
0.6 Remote Similarity NPC601710
0.593 Remote Similarity NPC88023
0.593 Remote Similarity NPC311830
0.593 Remote Similarity NPC309025
0.5783 Remote Similarity NPC143851
0.5747 Remote Similarity NPC602805
0.5714 Remote Similarity NPC93337
0.5714 Remote Similarity NPC95090
0.5714 Remote Similarity NPC27408
0.5698 Remote Similarity NPC191306
0.5647 Remote Similarity NPC105025
0.5647 Remote Similarity NPC603655
0.5632 Remote Similarity NPC22832
0.5632 Remote Similarity NPC243930
0.5632 Remote Similarity NPC601144
0.5632 Remote Similarity NPC606560
0.5595 Remote Similarity NPC58053
0.5595 Remote Similarity NPC261866
0.5595 Remote Similarity NPC39360
0.5595 Remote Similarity NPC29763
0.5595 Remote Similarity NPC210003
0.5568 Remote Similarity NPC607707
0.5529 Remote Similarity NPC146792
0.5517 Remote Similarity NPC479401
0.5517 Remote Similarity NPC609451
0.5465 Remote Similarity NPC186807
0.5465 Remote Similarity NPC45638
0.5455 Remote Similarity NPC605067
0.5412 Remote Similarity NPC45618
0.5402 Remote Similarity NPC201292
0.5393 Remote Similarity NPC206123
0.5349 Remote Similarity NPC259152
0.5349 Remote Similarity NPC189142
0.5349 Remote Similarity NPC77660
0.5333 Remote Similarity NPC203050
0.5333 Remote Similarity NPC225434
0.5287 Remote Similarity NPC58716
0.5172 Remote Similarity NPC168822
0.5165 Remote Similarity NPC601586
0.5135 Remote Similarity NPC47815
0.5135 Remote Similarity NPC194281
0.5111 Remote Similarity NPC101026
0.5111 Remote Similarity NPC120099
0.5111 Remote Similarity NPC488077
0.5111 Remote Similarity NPC197285
0.5111 Remote Similarity NPC609478
0.5065 Remote Similarity NPC287101
0.5056 Remote Similarity NPC472459

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC222936 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