Natural Product: NPC254741

Natural Product IDNPC254741
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(4-Methoxyphenyl)-7-(3-Methylbut-2-Enoxy)Chromen-4-One
IUPAC Name 3-(4-methoxyphenyl)-7-(3-methylbut-2-enoxy)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3581069
PubChem CID 177731
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 XZMVXCSKRYOMID-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O4/c1-14(2)10-11-24-17-8-9-18-20(12-17)25-13-19(21(18)22)15-4-6-16(23-3)7-5-15/h4-10,12-13H,11H2,1-3H3
SMILES CC(=CCOc1ccc2c(c1)occ(c1ccc(cc1)OC)c2=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.14 Volume:   357.536
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Van der Waals volume.
Dense:   0.94 LogP:   4.325
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.848
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.14
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   48.67
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.627 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.218 Fsp3:   0.19
MCE-18:   17.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.967 Fluc inhibitor:   0.99
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.943
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.777
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.387 Promiscuous compounds:   0.102

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.655 MDCK Permeability:   -4.622
Pgp-inhibitor:   0.794 Pgp-substrate:   0.055
PAMPA:   0.363
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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):   0.457
20% Bioavailability (F20%):   0.299 30% Bioavailability (F30%):   0.574
50% Bioavailability (F50%):   0.758

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.773
Plasma Protein Binding (PPB):   94.996% Volume Distribution (VD):   0.02
Fu: 4.011%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.905
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.843
BSEP inhibitor:   0.941

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.063 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.971
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.038
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.902 CYP2C8-inhibitor:   1.0
HLM stability:   0.404
?
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):  7.577 Half-life (T1/2):  0.589

ADMET: Toxicity

hERG Blockers:  0.464 hERG Blockers (10um):  0.682
Human Hepatotoxicity (H-HT):  0.58 Drug-induced Liver Injury (DILI):  0.895
AMES Toxicity:  0.595 Rat Oral Acute Toxicity:  0.384
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.377
Carcinogencity:  0.801 Eye Corrosion:  0.013
Eye Irritation:  0.834 Respiratory Toxicity:  0.803
Drug-induced Neurotoxicity:  0.557 Ototoxicity:  0.347
Hematotoxicity:  0.409 Drug-induced Nephrotoxicity:  0.477
Genotoxicity:  0.312 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.136 Hek293 Cytotoxicity:  0.338
BCF:   2.095
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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:   4.577
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.314
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.827
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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
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO33696 Millettia oblata ssp. teitensis Species Fabaceae Eukaryota leaves Ngangao Forest, Taita Hill, Taita County, Kenya 2014-JUL PMID[28665590]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]

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
NPT34 Cell line BV-2 Mus musculus IC50 > 100000.0 nM PMID[25466192]
NPT34 Cell line BV-2 Mus musculus IC50 = 45200.0 nM PMID[29482940]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 33300.0 nM PMID[28665590]

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 NPC254741 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
0.8448 Intermediate Similarity NPC185401
0.7736 Intermediate Similarity NPC182428
0.7576 Intermediate Similarity NPC478528
0.7368 Intermediate Similarity NPC136095
0.6935 Remote Similarity NPC13967
0.6875 Remote Similarity NPC133400
0.6667 Remote Similarity NPC471590
0.6618 Remote Similarity NPC607700
0.6615 Remote Similarity NPC249824
0.6441 Remote Similarity NPC185607
0.6333 Remote Similarity NPC479067
0.6308 Remote Similarity NPC203636
0.623 Remote Similarity NPC181124
0.6207 Remote Similarity NPC120924
0.5968 Remote Similarity NPC186507
0.5938 Remote Similarity NPC602183
0.5902 Remote Similarity NPC474264
0.589 Remote Similarity NPC229847
0.5857 Remote Similarity NPC488570
0.5857 Remote Similarity NPC608710
0.5806 Remote Similarity NPC603503
0.5733 Remote Similarity NPC5840
0.5714 Remote Similarity NPC209560
0.5714 Remote Similarity NPC490700
0.5574 Remote Similarity NPC223354
0.5556 Remote Similarity NPC474340
0.5556 Remote Similarity NPC216314
0.5541 Remote Similarity NPC45165
0.5522 Remote Similarity NPC478987
0.5513 Remote Similarity NPC43761
0.5507 Remote Similarity NPC488135
0.5469 Remote Similarity NPC121522
0.5467 Remote Similarity NPC233502
0.5405 Remote Similarity NPC487214
0.5342 Remote Similarity NPC25547
0.5312 Remote Similarity NPC10467
0.5312 Remote Similarity NPC116632
0.5312 Remote Similarity NPC333691
0.5278 Remote Similarity NPC479305
0.5217 Remote Similarity NPC606446
0.5217 Remote Similarity NPC607923
0.5128 Remote Similarity NPC189270
0.5079 Remote Similarity NPC195919
0.5077 Remote Similarity NPC35763

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC254741 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
0.6333 Remote Similarity NPD2796 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