Natural Product: NPC84265

Natural Product IDNPC84265
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6-Hydroxykaempferol 7-O-Glucoside
IUPAC Name 3,5,6-trihydroxy-2-(4-hydroxyphenyl)-7-[(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 CHEMBL462992
PubChem CID 5318240
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003533] Flavonoid-7-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 IYEWEDZIDUAUTD-HSOQPIRZSA-N
Standard InCHI InChI=1S/C21H20O12/c22-6-11-14(25)17(28)19(30)21(33-11)32-10-5-9-12(15(26)13(10)24)16(27)18(29)20(31-9)7-1-3-8(23)4-2-7/h1-5,11,14,17,19,21-26,28-30H,6H2/t11-,14-,17+,19-,21-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2cc3oc(c4ccc(cc4)O)c(c(=O)c3c(c2O)O)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   0.433
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.129
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.827
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   210.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.229 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.024 Fsp3:   0.286
MCE-18:   91.0
?
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:   1
Colloidal aggregators:   0.654 Fluc inhibitor:   0.287
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.863
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.642
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.283 Promiscuous compounds:   0.916

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.443 MDCK Permeability:   -4.933
Pgp-inhibitor:   0.001 Pgp-substrate:   0.118
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):   0.81
20% Bioavailability (F20%):   0.127 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.442
Plasma Protein Binding (PPB):   84.465% Volume Distribution (VD):   -0.123
Fu: 11.975%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.91
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.789
HLM stability:   0.105
?
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):  3.17 Half-life (T1/2):  4.1

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.117
Human Hepatotoxicity (H-HT):  0.618 Drug-induced Liver Injury (DILI):  0.944
AMES Toxicity:  0.818 Rat Oral Acute Toxicity:  0.038
Maximum Recommended Daily Dose:  0.05 Skin Sensitization:  0.995
Carcinogencity:  0.307 Eye Corrosion:  0.0
Eye Irritation:  0.545 Respiratory Toxicity:  0.016
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.852
Hematotoxicity:  0.143 Drug-induced Nephrotoxicity:  0.262
Genotoxicity:  0.893 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.338 Hek293 Cytotoxicity:  0.367
BCF:   0.401
?
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:   2.964
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.359
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.692
?
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
NPO5129 Tagetes lucida Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[12502312]
NPO21413 Armillaria tabescens Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3676 Fusarium sambucinum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8 Buphthalmum salicifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4578 Cystoseira fimbriata Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9781 Hyphear tanakae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO21413 Armillaria tabescens Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8 Buphthalmum salicifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21413 Armillaria tabescens Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4578 Cystoseira fimbriata Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3676 Fusarium sambucinum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9150 Polypodiodes formosana Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9781 Hyphear tanakae n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO5129 Tagetes lucida Species Asteraceae 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
NPT1 Others Radical scavenging activity n.a. EC50 = 6.9 ug PMID[12502312]

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 NPC84265 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
0.8857 High Similarity NPC245014
0.7703 Intermediate Similarity NPC146792
0.7703 Intermediate Similarity NPC323593
0.7703 Intermediate Similarity NPC203500
0.7692 Intermediate Similarity NPC477848
0.6923 Remote Similarity NPC58716
0.6795 Remote Similarity NPC277205
0.6795 Remote Similarity NPC37919
0.6707 Remote Similarity NPC601586
0.6667 Remote Similarity NPC45618
0.6667 Remote Similarity NPC197285
0.6625 Remote Similarity NPC117260
0.6543 Remote Similarity NPC285197
0.6522 Remote Similarity NPC599948
0.6463 Remote Similarity NPC486578
0.6456 Remote Similarity NPC108831
0.6456 Remote Similarity NPC182634
0.642 Remote Similarity NPC21100
0.6341 Remote Similarity NPC307938
0.631 Remote Similarity NPC469931
0.6173 Remote Similarity NPC609879
0.6049 Remote Similarity NPC39360
0.6049 Remote Similarity NPC476405
0.6049 Remote Similarity NPC29763
0.6049 Remote Similarity NPC210003
0.5976 Remote Similarity NPC282987
0.5976 Remote Similarity NPC93337
0.5976 Remote Similarity NPC297987
0.5955 Remote Similarity NPC183672
0.5904 Remote Similarity NPC24043
0.5904 Remote Similarity NPC105025
0.5895 Remote Similarity NPC603856
0.5854 Remote Similarity NPC77672
0.5854 Remote Similarity NPC133671
0.5854 Remote Similarity NPC135391
0.5854 Remote Similarity NPC78263
0.5854 Remote Similarity NPC250069
0.5778 Remote Similarity NPC3583
0.5714 Remote Similarity NPC488080
0.5714 Remote Similarity NPC169733
0.5714 Remote Similarity NPC169977
0.5663 Remote Similarity NPC254306
0.5663 Remote Similarity NPC83283
0.5663 Remote Similarity NPC238376
0.5632 Remote Similarity NPC116458
0.5632 Remote Similarity NPC246943
0.5529 Remote Similarity NPC304745
0.5529 Remote Similarity NPC610763
0.5517 Remote Similarity NPC601144
0.5517 Remote Similarity NPC601710
0.5412 Remote Similarity NPC145038
0.5412 Remote Similarity NPC8573
0.5412 Remote Similarity NPC56077
0.5412 Remote Similarity NPC281131
0.5412 Remote Similarity NPC253662
0.5412 Remote Similarity NPC179950
0.5412 Remote Similarity NPC136042
0.5412 Remote Similarity NPC88789
0.5412 Remote Similarity NPC259152
0.5412 Remote Similarity NPC189142
0.5412 Remote Similarity NPC77660
0.5412 Remote Similarity NPC491374
0.5349 Remote Similarity NPC84362
0.5349 Remote Similarity NPC45638
0.5326 Remote Similarity NPC275454
0.5294 Remote Similarity NPC261866
0.5287 Remote Similarity NPC201292
0.5281 Remote Similarity NPC136761
0.5281 Remote Similarity NPC311830
0.5281 Remote Similarity NPC602805
0.5258 Remote Similarity NPC80068
0.5233 Remote Similarity NPC197896
0.5233 Remote Similarity NPC313163
0.5227 Remote Similarity NPC168584
0.5227 Remote Similarity NPC191306
0.5227 Remote Similarity NPC60735
0.5227 Remote Similarity NPC26230
0.5227 Remote Similarity NPC488071
0.5222 Remote Similarity NPC203050
0.5222 Remote Similarity NPC488072
0.5222 Remote Similarity NPC225434
0.5169 Remote Similarity NPC101026
0.5169 Remote Similarity NPC43211
0.5169 Remote Similarity NPC488077
0.5169 Remote Similarity NPC605067
0.5169 Remote Similarity NPC609478
0.5158 Remote Similarity NPC64425
0.5152 Remote Similarity NPC135358
0.5119 Remote Similarity NPC288084
0.5119 Remote Similarity NPC268193
0.5116 Remote Similarity NPC289667
0.5116 Remote Similarity NPC58053
0.5116 Remote Similarity NPC143851
0.5114 Remote Similarity NPC42773
0.5114 Remote Similarity NPC205076
0.5114 Remote Similarity NPC45522
0.5114 Remote Similarity NPC599850
0.5111 Remote Similarity NPC206123
0.5111 Remote Similarity NPC605784
0.5111 Remote Similarity NPC607707
0.5109 Remote Similarity NPC472607
0.5098 Remote Similarity NPC480796
0.5057 Remote Similarity NPC64305
0.5057 Remote Similarity NPC168822
0.5057 Remote Similarity NPC95090
0.5057 Remote Similarity NPC27408
0.5056 Remote Similarity NPC609451
0.5053 Remote Similarity NPC131745
0.5051 Remote Similarity NPC287889

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC84265 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