Natural Product: NPC64051

Natural Product IDNPC64051
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Apigenin-7-o-(6”-o-malonyl)-glucoside
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 JXWAQRJFONLTSI-ASDZUOGYSA-N
Standard InCHI InChI=1S/C24H22O13/c25-11-3-1-10(2-4-11)15-7-14(27)20-13(26)5-12(6-16(20)36-15)35-24-23(33)22(32)21(31)17(37-24)9-34-19(30)8-18(28)29/h1-7,17,21-26,31-33H,8-9H2,(H,28,29)/t17-,21-,22+,23-,24-/m1/s1
SMILES O=C(O)CC(OC[C@H]1O[C@@H](OC2=CC3=C(C(C=C(C4=CC=C(O)C=C4)O3)=O)C(O)=C2)[C@H](O)[C@@H](O)[C@@H]1O)=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   518.11 Volume:   477.343
?
Van der Waals volume.
Dense:   1.085 LogP:   0.591
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.22
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.238
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   26.0
TPSA:   213.42
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.181 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.024 Fsp3:   0.292
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.509 Fluc inhibitor:   0.366
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.962
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.852
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.076 Promiscuous compounds:   0.45

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.383 MDCK Permeability:   -5.103
Pgp-inhibitor:   0.0 Pgp-substrate:   0.036
PAMPA:   1.0
?
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):   0.028
20% Bioavailability (F20%):   0.052 30% Bioavailability (F30%):   0.393
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.365
Plasma Protein Binding (PPB):   82.044% Volume Distribution (VD):   -0.099
Fu: 16.965%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.018
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.026
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.914
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
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):  1.192 Half-life (T1/2):  2.919

ADMET: Toxicity

hERG Blockers:  0.009 hERG Blockers (10um):  0.046
Human Hepatotoxicity (H-HT):  0.413 Drug-induced Liver Injury (DILI):  0.988
AMES Toxicity:  0.617 Rat Oral Acute Toxicity:  0.101
Maximum Recommended Daily Dose:  0.141 Skin Sensitization:  0.943
Carcinogencity:  0.165 Eye Corrosion:  0.0
Eye Irritation:  0.77 Respiratory Toxicity:  0.048
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.619
Hematotoxicity:  0.117 Drug-induced Nephrotoxicity:  0.597
Genotoxicity:  0.979 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.033 Hek293 Cytotoxicity:  0.144
BCF:   0.257
?
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:   2.786
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.178
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.353
?
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
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2009.03.042]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.3136/fstr.15.499]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.5897/AJB10.140]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.5897/AJB2010.000-3252]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers Tongxiang, China n.a. PMID[24621197]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. PMID[28248102]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20440 Chrysanthemum x morifolium 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
NPO20440 Chrysanthemum x morifolium n.a. Flowers 1.56 n.a. n.a. mg/g of FW DOI[10.3136/fstr.15.499]

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
NPT2797 Individual protein Pancreatic lipase Homo sapiens Inhibition = 35.0 % PMID[37099836]
NPT2797 Individual protein Pancreatic lipase Homo sapiens Inhibition = 47.2 % PMID[37099836]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Activity = 73.0 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 74.9 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 52.2 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 55.1 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 67.3 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity n.a. n.a. n.a. PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 54.7 % PMID[37099836]
NPT65 Cell line HepG2 Homo sapiens Activity = 48.6 % PMID[37099836]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[37099836]
NPT28438 Unchecked Unchecked n.a. Activity = 23.68 % PMID[37099836]
NPT28438 Unchecked Unchecked n.a. Activity = 22.44 % PMID[37099836]
NPT28438 Unchecked Unchecked n.a. Activity = 18.03 % PMID[37099836]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[37099836]





 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 NPC64051 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
0.9036 High Similarity NPC229409
0.8795 High Similarity NPC46202
0.7473 Intermediate Similarity NPC270675
0.7473 Intermediate Similarity NPC195685
0.7386 Intermediate Similarity NPC44931
0.7234 Intermediate Similarity NPC472994
0.7059 Intermediate Similarity NPC27942
0.6988 Remote Similarity NPC331652
0.6947 Remote Similarity NPC101636
0.6947 Remote Similarity NPC298171
0.6939 Remote Similarity NPC472993
0.6915 Remote Similarity NPC479766
0.6905 Remote Similarity NPC39360
0.6905 Remote Similarity NPC29763
0.6905 Remote Similarity NPC210003
0.6842 Remote Similarity NPC479765
0.6782 Remote Similarity NPC282169
0.6735 Remote Similarity NPC121703
0.6667 Remote Similarity NPC172807
0.6559 Remote Similarity NPC22062
0.6559 Remote Similarity NPC473634
0.6559 Remote Similarity NPC210073
0.6559 Remote Similarity NPC138811
0.6374 Remote Similarity NPC190003
0.6354 Remote Similarity NPC65711
0.6289 Remote Similarity NPC473623
0.6224 Remote Similarity NPC488089
0.618 Remote Similarity NPC181712
0.6162 Remote Similarity NPC80068
0.6136 Remote Similarity NPC19709
0.6122 Remote Similarity NPC209296
0.6067 Remote Similarity NPC95090
0.6067 Remote Similarity NPC27408
0.6067 Remote Similarity NPC189142
0.6067 Remote Similarity NPC77660
0.6044 Remote Similarity NPC20505
0.5979 Remote Similarity NPC186816
0.5978 Remote Similarity NPC601144
0.5978 Remote Similarity NPC608742
0.5957 Remote Similarity NPC211594
0.5914 Remote Similarity NPC311830
0.5895 Remote Similarity NPC254540
0.5882 Remote Similarity NPC179862
0.5849 Remote Similarity NPC277532
0.5842 Remote Similarity NPC477629
0.578 Remote Similarity NPC298666
0.5778 Remote Similarity NPC261866
0.5714 Remote Similarity NPC473512
0.5714 Remote Similarity NPC129827
0.5667 Remote Similarity NPC473043
0.566 Remote Similarity NPC480796
0.566 Remote Similarity NPC473278
0.5638 Remote Similarity NPC22832
0.5638 Remote Similarity NPC243930
0.5619 Remote Similarity NPC11468
0.5604 Remote Similarity NPC249281
0.5604 Remote Similarity NPC108831
0.5604 Remote Similarity NPC182634
0.5579 Remote Similarity NPC607707
0.5556 Remote Similarity NPC65003
0.5543 Remote Similarity NPC297987
0.5543 Remote Similarity NPC323593
0.5543 Remote Similarity NPC203500
0.5521 Remote Similarity NPC276377
0.55 Remote Similarity NPC234133
0.5484 Remote Similarity NPC46420
0.5464 Remote Similarity NPC477848
0.5455 Remote Similarity NPC67105
0.5376 Remote Similarity NPC93337
0.5376 Remote Similarity NPC146792
0.5364 Remote Similarity NPC488087
0.5351 Remote Similarity NPC209550
0.5347 Remote Similarity NPC122809
0.5347 Remote Similarity NPC204693
0.534 Remote Similarity NPC72016
0.5319 Remote Similarity NPC105025
0.5312 Remote Similarity NPC43211
0.5288 Remote Similarity NPC486577
0.5283 Remote Similarity NPC253685
0.5268 Remote Similarity NPC488086
0.5258 Remote Similarity NPC116458
0.5258 Remote Similarity NPC246943
0.5253 Remote Similarity NPC606546
0.5248 Remote Similarity NPC150164
0.5192 Remote Similarity NPC210961
0.5192 Remote Similarity NPC483707
0.5175 Remote Similarity NPC471030
0.5158 Remote Similarity NPC610763
0.5152 Remote Similarity NPC116864
0.5152 Remote Similarity NPC244776
0.5133 Remote Similarity NPC68592
0.5106 Remote Similarity NPC238376
0.5106 Remote Similarity NPC143851
0.5104 Remote Similarity NPC198324
0.51 Remote Similarity NPC8856
0.5098 Remote Similarity NPC479405
0.5098 Remote Similarity NPC303913
0.5094 Remote Similarity NPC85751
0.5094 Remote Similarity NPC475382
0.5094 Remote Similarity NPC19240
0.5053 Remote Similarity NPC277205
0.5053 Remote Similarity NPC37919
0.5053 Remote Similarity NPC136042
0.505 Remote Similarity NPC295613
0.505 Remote Similarity NPC473657
0.5049 Remote Similarity NPC129264
0.5049 Remote Similarity NPC479404
0.5045 Remote Similarity NPC473644

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC64051 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
0.6122 Remote Similarity NPD7054 Phase 4
0.5094 Remote Similarity NPD7251 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