Natural Product: NPC53181

Natural Product IDNPC53181
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid500772
IUPAC Name 5-hydroxy-7-methoxy-6,8-dimethyl-2-phenylchromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL51162
PubChem CID 369598
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 PQZXFPBMXPGZMO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O4/c1-10-16(20)15-13(19)9-14(12-7-5-4-6-8-12)22-18(15)11(2)17(10)21-3/h4-9,20H,1-3H3
SMILES COc1c(C)c2oc(cc(=O)c2c(c1C)O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.1 Volume:   308.284
?
Van der Waals volume.
Dense:   0.96 LogP:   3.953
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.269
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.989
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.781 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.314 Fsp3:   0.167
MCE-18:   18.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.47 Fluc inhibitor:   0.729
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.773
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.794
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.315 Promiscuous compounds:   0.356

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.875 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.968 Pgp-substrate:   0.13
PAMPA:   0.181
?
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):   0.002
20% Bioavailability (F20%):   0.045 30% Bioavailability (F30%):   0.155
50% Bioavailability (F50%):   0.611

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.744 MRP1:   0.985
Plasma Protein Binding (PPB):   98.518% Volume Distribution (VD):   -0.129
Fu: 0.972%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.74
OATP1B3 inhibitor:   0.942 BCRP inhibitor:   0.829
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.843 CYP1A2-substrate:   0.577
CYP2C19-inhibitor:   0.078 CYP2C19-substrate:   0.026
CYP2C9-inhibitor:   0.943 CYP2C9-substrate:   0.016
CYP2D6-inhibitor:   0.829 CYP2D6-substrate:   0.506
CYP3A4-inhibitor:   0.974 CYP3A4-substrate:   0.335
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.822
HLM stability:   0.619
?
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):  4.03 Half-life (T1/2):  0.901

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.475
Human Hepatotoxicity (H-HT):  0.537 Drug-induced Liver Injury (DILI):  0.791
AMES Toxicity:  0.531 Rat Oral Acute Toxicity:  0.532
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.677
Carcinogencity:  0.755 Eye Corrosion:  0.155
Eye Irritation:  0.978 Respiratory Toxicity:  0.77
Drug-induced Neurotoxicity:  0.187 Ototoxicity:  0.105
Hematotoxicity:  0.26 Drug-induced Nephrotoxicity:  0.128
Genotoxicity:  0.859 RPMI-8226 Immunitoxicity:  0.084
A549 Cytotoxicity:  0.206 Hek293 Cytotoxicity:  0.491
BCF:   1.484
?
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:   4.164
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.938
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.602
?
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
NPO33071 desmos spp. Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12729671]

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
NPT759 Cell line H9 Homo sapiens IC50 = 19.8 ug.mL-1 PMID[14640513]
NPT517 Cell line Panel NCI-60 (60 carcinoma cell lines) Homo sapiens GI50 > 100000.0 nM PMID[20303767]
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 100000.0 nM PMID[23398362]
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 100000.0 nM PMID[20553004]
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 100000.0 nM PMID[10924160]
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 100000.0 nM PMID[17848089]
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 100000.0 nM Open TG-GATES in vivo data: Biochemistry
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 100000.0 nM PMID[26083682]
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 100000.0 nM PMID[11975515]
NPT111 Cell line K562 Homo sapiens GI50 n.a. 100000.0 nM PMID[17488128]
NPT376 Cell line A498 Homo sapiens GI50 n.a. 100000.0 nM PMID[21982796]
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 100000.0 nM PMID[10869208]
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vitro pharmacology data
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 100000.0 nM PMID[20112996]
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 100000.0 nM PMID[19715320]
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 100000.0 nM PMID[8864235]
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 100000.0 nM PMID[23265253]
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vitro pharmacology data
NPT573 Cell line M19-MEL Homo sapiens GI50 n.a. 100000.0 nM PMID[23398362]
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 100000.0 nM PMID[16499328]
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 100000.0 nM PMID[1875350]
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 100000.0 nM PMID[20205479]
NPT387 Cell line M14 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 100000.0 nM PMID[15332848]
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 100000.0 nM PMID[19403314]
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 100000.0 nM PMID[23734701]
NPT81 Cell line A549 Homo sapiens GI50 n.a. 100000.0 nM PMID[18183025]
NPT575 Cell line KM-20L2 Homo sapiens GI50 n.a. 100000.0 nM PMID[23398362]
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 100000.0 nM PMID[21353775]
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 100000.0 nM PMID[8277313]
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 100000.0 nM PMID[20149652]
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 100000.0 nM PMID[24099304]
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 100000.0 nM PMID[20061158]
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 100000.0 nM PMID[18341287]
NPT731 Cell line LXFL 529 Homo sapiens GI50 n.a. 100000.0 nM PMID[15679323]
NPT576 Cell line DMS-114 Homo sapiens GI50 n.a. 100000.0 nM PMID[23910596]
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 100000.0 nM PMID[19405508]
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 100000.0 nM PMID[16378364]
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 100000.0 nM PMID[1336040]
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 100000.0 nM PMID[20337497]
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 100000.0 nM PMID[23398362]
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 100000.0 nM PMID[22071302]
NPT577 Cell line RXF 631 Homo sapiens GI50 n.a. 100000.0 nM PMID[16989532]
NPT578 Cell line SNB-78 Homo sapiens GI50 n.a. 100000.0 nM PMID[21053938]
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 100000.0 nM PMID[9514009]
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 100000.0 nM PMID[20143778]
NPT579 Cell line DLD-1 Homo sapiens GI50 n.a. 100000.0 nM PMID[23993676]
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 100000.0 nM PMID[7852999]
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 100000.0 nM PMID[19114678]
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 100000.0 nM PMID[26003344]
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 100000.0 nM PMID[23350733]
NPT732 Cell line HOP-18 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set

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 NPC53181 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
0.8235 Intermediate Similarity NPC159275
0.7037 Intermediate Similarity NPC18260
0.6316 Remote Similarity NPC217186
0.614 Remote Similarity NPC606332
0.5789 Remote Similarity NPC293183
0.5789 Remote Similarity NPC131624
0.5789 Remote Similarity NPC602963
0.5763 Remote Similarity NPC78913
0.569 Remote Similarity NPC306821
0.569 Remote Similarity NPC275722
0.569 Remote Similarity NPC127447
0.569 Remote Similarity NPC187498
0.569 Remote Similarity NPC239128
0.5614 Remote Similarity NPC201395
0.5362 Remote Similarity NPC486091
0.5167 Remote Similarity NPC488084
0.5167 Remote Similarity NPC482122
0.5167 Remote Similarity NPC194281
0.5167 Remote Similarity NPC609062
0.5088 Remote Similarity NPC259713
0.5079 Remote Similarity NPC606140
0.5079 Remote Similarity NPC608539

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC53181 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