Natural Product: NPC477848

Natural Product IDNPC477848
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-(6''-acetyl-beta-D-glucopyranoside)
IUPAC Name [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[3,5,6-trihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoxan-2-yl]methyl acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11318115
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 SCWWMMAIPAUYGU-SDBRSXMQSA-N
Standard InCHI InChI=1S/C23H22O13/c1-8(24)33-7-13-16(27)19(30)21(32)23(36-13)35-12-6-11-14(17(28)15(12)26)18(29)20(31)22(34-11)9-2-4-10(25)5-3-9/h2-6,13,16,19,21,23,25-28,30-32H,7H2,1H3/t13-,16-,19+,21-,23-/m1/s1
SMILES CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)OC2=C(C(=C3C(=C2)OC(=C(C3=O)O)C4=CC=C(C=C4)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   506.11 Volume:   462.683
?
Van der Waals volume.
Dense:   1.094 LogP:   0.416
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.991
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.597
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   25.0
TPSA:   216.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.18 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.094 Fsp3:   0.304
MCE-18:   93.333
?
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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.557 Fluc inhibitor:   0.289
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.86
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.8
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.062 Promiscuous compounds:   0.703

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.557 MDCK Permeability:   -5.094
Pgp-inhibitor:   0.007 Pgp-substrate:   0.331
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):   0.237
20% Bioavailability (F20%):   0.198 30% Bioavailability (F30%):   0.988
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.512
Plasma Protein Binding (PPB):   84.328% Volume Distribution (VD):   -0.187
Fu: 14.633%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.915
BSEP inhibitor:   0.133

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.009
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.012
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.99
HLM stability:   0.886
?
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):  2.423 Half-life (T1/2):  3.177

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.229
Human Hepatotoxicity (H-HT):  0.452 Drug-induced Liver Injury (DILI):  0.938
AMES Toxicity:  0.777 Rat Oral Acute Toxicity:  0.099
Maximum Recommended Daily Dose:  0.057 Skin Sensitization:  0.983
Carcinogencity:  0.189 Eye Corrosion:  0.001
Eye Irritation:  0.818 Respiratory Toxicity:  0.014
Drug-induced Neurotoxicity:  0.008 Ototoxicity:  0.458
Hematotoxicity:  0.093 Drug-induced Nephrotoxicity:  0.269
Genotoxicity:  0.87 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.453 Hek293 Cytotoxicity:  0.212
BCF:   0.512
?
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:   3.208
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.49
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.986
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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
NPO223 Rhaponticum carthamoides Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15730237]
NPO223 Rhaponticum carthamoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO223 Rhaponticum carthamoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO223 Rhaponticum carthamoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO223 Rhaponticum carthamoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO223 Rhaponticum carthamoides 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. Inhibition = 75 % PMID[15730237]
NPT1 Others Radical scavenging activity n.a. Inhibition = 36 % PMID[15730237]

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 NPC477848 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
0.7753 Intermediate Similarity NPC599948
0.7692 Intermediate Similarity NPC84265
0.7065 Intermediate Similarity NPC603856
0.6829 Remote Similarity NPC245014
0.6383 Remote Similarity NPC80068
0.6364 Remote Similarity NPC172807
0.6264 Remote Similarity NPC233994
0.619 Remote Similarity NPC108831
0.619 Remote Similarity NPC182634
0.6162 Remote Similarity NPC480796
0.6064 Remote Similarity NPC211532
0.6064 Remote Similarity NPC488364
0.593 Remote Similarity NPC146792
0.593 Remote Similarity NPC323593
0.593 Remote Similarity NPC203500
0.5824 Remote Similarity NPC116864
0.5824 Remote Similarity NPC244776
0.5814 Remote Similarity NPC476405
0.5806 Remote Similarity NPC67105
0.5761 Remote Similarity NPC254540
0.5699 Remote Similarity NPC187379
0.5625 Remote Similarity NPC153755
0.5567 Remote Similarity NPC470443
0.5484 Remote Similarity NPC211594
0.5464 Remote Similarity NPC64051
0.5455 Remote Similarity NPC238376
0.5368 Remote Similarity NPC609888
0.5333 Remote Similarity NPC58716
0.5326 Remote Similarity NPC181616
0.5326 Remote Similarity NPC226722
0.5312 Remote Similarity NPC44931
0.5312 Remote Similarity NPC227508
0.53 Remote Similarity NPC270675
0.53 Remote Similarity NPC195685
0.5294 Remote Similarity NPC135358
0.5258 Remote Similarity NPC65563
0.5258 Remote Similarity NPC470949
0.5222 Remote Similarity NPC277205
0.5222 Remote Similarity NPC37919
0.5217 Remote Similarity NPC285197
0.5213 Remote Similarity NPC601586
0.5204 Remote Similarity NPC186816
0.5196 Remote Similarity NPC101636
0.5196 Remote Similarity NPC298171
0.5196 Remote Similarity NPC287889
0.5192 Remote Similarity NPC121703
0.5161 Remote Similarity NPC197285
0.5161 Remote Similarity NPC486578
0.5155 Remote Similarity NPC173582
0.5155 Remote Similarity NPC265885
0.5155 Remote Similarity NPC181465
0.5155 Remote Similarity NPC215710
0.5155 Remote Similarity NPC275454
0.5155 Remote Similarity NPC473438
0.5155 Remote Similarity NPC253788
0.5146 Remote Similarity NPC472994
0.5132 Remote Similarity NPC192229
0.5111 Remote Similarity NPC45618
0.5109 Remote Similarity NPC21100
0.5109 Remote Similarity NPC117260
0.5098 Remote Similarity NPC470447
0.5098 Remote Similarity NPC85751
0.5098 Remote Similarity NPC19240
0.5094 Remote Similarity NPC472993
0.5052 Remote Similarity NPC471079
0.5051 Remote Similarity NPC473571
0.5051 Remote Similarity NPC110941
0.5049 Remote Similarity NPC36138
0.5049 Remote Similarity NPC470449

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477848 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