Natural Product: NPC181250

Natural Product IDNPC181250
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,5,6,7,3',4',5'-Heptamethoxyflavone
IUPAC Name 3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3109440
PubChem CID 389001
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 SHRSLVWLFNSTLK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H24O9/c1-24-13-8-11(9-14(25-2)19(13)27-4)18-22(30-7)17(23)16-12(31-18)10-15(26-3)20(28-5)21(16)29-6/h8-10H,1-7H3
SMILES COc1c(OC)cc(cc1OC)c1oc2cc(OC)c(c(c2c(=O)c1OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.14 Volume:   421.419
?
Van der Waals volume.
Dense:   1.025 LogP:   2.116
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.437
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.256
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   18.0
TPSA:   94.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.53 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.472 Fsp3:   0.318
MCE-18:   21.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.016 Fluc inhibitor:   0.324
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.823
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.628
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.405 Promiscuous compounds:   0.363

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.489 MDCK Permeability:   -4.513
Pgp-inhibitor:   0.995 Pgp-substrate:   0.045
PAMPA:   0.013
?
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):   0.022
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.013
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.205 MRP1:   0.969
Plasma Protein Binding (PPB):   92.011% Volume Distribution (VD):   -0.276
Fu: 6.655%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.032
OATP1B3 inhibitor:   0.942 BCRP inhibitor:   0.864
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.378
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.8
CYP2C9-inhibitor:   0.899 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.923 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.017
CYP2B6-substrate:   0.028 CYP2C8-inhibitor:   0.662
HLM stability:   0.324
?
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):  5.962 Half-life (T1/2):  1.23

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.532
Human Hepatotoxicity (H-HT):  0.456 Drug-induced Liver Injury (DILI):  0.715
AMES Toxicity:  0.262 Rat Oral Acute Toxicity:  0.327
Maximum Recommended Daily Dose:  0.307 Skin Sensitization:  0.478
Carcinogencity:  0.812 Eye Corrosion:  0.435
Eye Irritation:  0.854 Respiratory Toxicity:  0.572
Drug-induced Neurotoxicity:  0.659 Ototoxicity:  0.258
Hematotoxicity:  0.543 Drug-induced Nephrotoxicity:  0.287
Genotoxicity:  0.071 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.117 Hek293 Cytotoxicity:  0.299
BCF:   2.094
?
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:   3.677
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.816
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.071
?
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
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO33509 byrsonima coccolobifolia Species Malpighiaceae Eukaryota leaves and stems cerrado at the Federal University of So Carlos (UFSCar), So Carlos, SP, Brazil 2011-Jul PMID[24521209]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[34964904]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36529712]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2715 Murraya paniculata Species Rutaceae 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
NPT1662 Individual protein Arginase Leishmania amazonensis IC50 = 127900.0 nM PMID[24521209]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT839 Cell line L6 Rattus norvegicus Activity = 81.2 % PMID[25659770]
NPT839 Cell line L6 Rattus norvegicus Activity = 93.8 % PMID[25659770]
NPT319 Cell line B16 Mus musculus IC50 > 100000.0 nM PMID[25659770]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia GI = 35.0 % PMID[25659770]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia IC50 = 5800.0 nM PMID[25659770]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 72.4 % PMID[25659770]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 25.9 % PMID[25659770]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia IC90 = 10800.0 nM PMID[25659770]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity > 100.0 uM PMID[25659770]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 31610.0 nM PMID[25659770]

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 NPC181250 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
0.7872 Intermediate Similarity NPC259058
0.7447 Intermediate Similarity NPC69752
0.7115 Intermediate Similarity NPC104459
0.7083 Intermediate Similarity NPC602291
0.6875 Remote Similarity NPC302408
0.68 Remote Similarity NPC607530
0.6667 Remote Similarity NPC34725
0.6471 Remote Similarity NPC472438
0.6364 Remote Similarity NPC131557
0.6316 Remote Similarity NPC122623
0.6226 Remote Similarity NPC76376
0.6102 Remote Similarity NPC241774
0.5926 Remote Similarity NPC610359
0.5902 Remote Similarity NPC276059
0.5902 Remote Similarity NPC280893
0.5806 Remote Similarity NPC257277
0.5741 Remote Similarity NPC215932
0.566 Remote Similarity NPC600022
0.5556 Remote Similarity NPC7973
0.5472 Remote Similarity NPC106461
0.5455 Remote Similarity NPC310259
0.5439 Remote Similarity NPC176300
0.537 Remote Similarity NPC14958
0.537 Remote Similarity NPC201547
0.5254 Remote Similarity NPC284353
0.5172 Remote Similarity NPC115798
0.5172 Remote Similarity NPC29841
0.5094 Remote Similarity NPC283002
0.5094 Remote Similarity NPC603362
0.5091 Remote Similarity NPC29536
0.5088 Remote Similarity NPC110070
0.5088 Remote Similarity NPC101830
0.5085 Remote Similarity NPC75215

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC181250 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