Natural Product: NPC6407

Natural Product IDNPC6407
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxy-4',7-Dimethoxy-Dihydroflavone
IUPAC Name 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462909
PubChem CID 321346
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 CKEXCBVNKRHAMX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-11-5-3-10(4-6-11)15-9-14(19)17-13(18)7-12(21-2)8-16(17)22-15/h3-8,15,18H,9H2,1-2H3
SMILES COc1ccc(cc1)C1CC(=O)c2c(O1)cc(cc2O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   3.12
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.162
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.389
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   64.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.943 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.621 Fsp3:   0.235
MCE-18:   54.238
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.436 Fluc inhibitor:   0.69
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.342
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.387
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.343 Promiscuous compounds:   0.025

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.889 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.997 Pgp-substrate:   0.013
PAMPA:   0.014
?
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):   0.144
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.352
50% Bioavailability (F50%):   0.95

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.258
Plasma Protein Binding (PPB):   93.113% Volume Distribution (VD):   0.08
Fu: 5.924%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.995
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.719 CYP2C19-substrate:   0.955
CYP2C9-inhibitor:   0.994 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.969 CYP2D6-substrate:   0.97
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.684
HLM stability:   0.986
?
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):  6.118 Half-life (T1/2):  0.872

ADMET: Toxicity

hERG Blockers:  0.228 hERG Blockers (10um):  0.559
Human Hepatotoxicity (H-HT):  0.636 Drug-induced Liver Injury (DILI):  0.845
AMES Toxicity:  0.771 Rat Oral Acute Toxicity:  0.492
Maximum Recommended Daily Dose:  0.523 Skin Sensitization:  0.338
Carcinogencity:  0.762 Eye Corrosion:  0.013
Eye Irritation:  0.954 Respiratory Toxicity:  0.821
Drug-induced Neurotoxicity:  0.548 Ototoxicity:  0.39
Hematotoxicity:  0.488 Drug-induced Nephrotoxicity:  0.739
Genotoxicity:  0.554 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.339 Hek293 Cytotoxicity:  0.542
BCF:   1.548
?
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:   3.962
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.351
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.58
?
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
NPO8788 Renealmia nicolaioides Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12444686]
NPO6544 Carpesium longifolium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[14695795]
NPO28807 Laggera pterodonta Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[20506820]
NPO28807 Laggera pterodonta Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[31664789]
NPO6544 Carpesium longifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28807 Laggera pterodonta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8788 Renealmia nicolaioides Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6544 Carpesium longifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6544 Carpesium longifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28807 Laggera pterodonta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6544 Carpesium longifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28807 Laggera pterodonta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8788 Renealmia nicolaioides Species Zingiberaceae 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
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD > 10.0 ug ml-1 PMID[12444686]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 200.0 ug.mL-1 PMID[14695795]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 200.0 ug.mL-1 PMID[14695795]

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 NPC6407 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
1.0 High Similarity NPC545184
0.8444 Intermediate Similarity NPC150648
0.8261 Intermediate Similarity NPC329203
0.8261 Intermediate Similarity NPC222342
0.7917 Intermediate Similarity NPC18727
0.75 Intermediate Similarity NPC274784
0.75 Intermediate Similarity NPC73028
0.75 Intermediate Similarity NPC20709
0.7391 Intermediate Similarity NPC140890
0.7222 Intermediate Similarity NPC477840
0.6863 Remote Similarity NPC310135
0.6863 Remote Similarity NPC469758
0.6531 Remote Similarity NPC188243
0.6531 Remote Similarity NPC110228
0.6452 Remote Similarity NPC219163
0.6383 Remote Similarity NPC99854
0.6275 Remote Similarity NPC20354
0.6275 Remote Similarity NPC162869
0.6154 Remote Similarity NPC156057
0.5926 Remote Similarity NPC601395
0.5926 Remote Similarity NPC602118
0.5849 Remote Similarity NPC480993
0.5849 Remote Similarity NPC296917
0.5849 Remote Similarity NPC170907
0.5818 Remote Similarity NPC302950
0.5769 Remote Similarity NPC32441
0.5769 Remote Similarity NPC243083
0.5769 Remote Similarity NPC13768
0.5769 Remote Similarity NPC287246
0.5769 Remote Similarity NPC79943
0.5741 Remote Similarity NPC475267
0.5686 Remote Similarity NPC144051
0.5686 Remote Similarity NPC135616
0.5667 Remote Similarity NPC480158
0.566 Remote Similarity NPC37392
0.5636 Remote Similarity NPC48208
0.5556 Remote Similarity NPC255106
0.5556 Remote Similarity NPC194432
0.5556 Remote Similarity NPC338131
0.5556 Remote Similarity NPC235165
0.549 Remote Similarity NPC485642
0.549 Remote Similarity NPC611561
0.5455 Remote Similarity NPC606248
0.5405 Remote Similarity NPC97285
0.5385 Remote Similarity NPC265871
0.5385 Remote Similarity NPC205093
0.537 Remote Similarity NPC484336
0.537 Remote Similarity NPC312391
0.537 Remote Similarity NPC484337
0.5345 Remote Similarity NPC236637
0.5333 Remote Similarity NPC271741
0.5333 Remote Similarity NPC148757
0.5323 Remote Similarity NPC108456
0.5303 Remote Similarity NPC97052
0.5303 Remote Similarity NPC64915
0.5283 Remote Similarity NPC225153
0.5283 Remote Similarity NPC182421
0.5283 Remote Similarity NPC479876
0.5273 Remote Similarity NPC482119
0.5273 Remote Similarity NPC482120
0.5273 Remote Similarity NPC324386
0.5246 Remote Similarity NPC470131
0.5246 Remote Similarity NPC470132
0.5224 Remote Similarity NPC39351
0.5185 Remote Similarity NPC204515
0.5179 Remote Similarity NPC321011
0.5179 Remote Similarity NPC294852
0.5179 Remote Similarity NPC469764
0.5179 Remote Similarity NPC188679
0.5167 Remote Similarity NPC109183
0.5111 Remote Similarity NPC305518
0.5091 Remote Similarity NPC177354
0.5088 Remote Similarity NPC599987
0.5082 Remote Similarity NPC69674
0.5082 Remote Similarity NPC477841
0.507 Remote Similarity NPC236934

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC6407 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
0.5818 Remote Similarity NPD1934 Phase 0
0.5769 Remote Similarity NPD1550 Phase 2
0.5769 Remote Similarity NPD1552 Clinical (unspecified phase)

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