Natural Product: NPC495472

Natural Product IDNPC495472
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one
IUPAC Name 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxy-3-[(2~{S},3~{R},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 HCHYKZURXGCQDJ-LYEUIUKESA-N
Standard InCHI InChI=1S/C24H26O11/c1-10-18(26)20(28)21(29)24(33-10)35-23-19(27)17-13(25)8-12(30-2)9-16(17)34-22(23)11-5-6-14(31-3)15(7-11)32-4/h5-10,18,20-21,24-26,28-29H,1-4H3/t10-,18-,20+,21+,24-/m0/s1
SMILES COC1=CC(O)=C2C(=O)C(O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](O)[C@H]3O)=C(C3=CC=C(OC)C(OC)=C3)OC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   490.15 Volume:   465.035
?
Van der Waals volume.
Dense:   1.054 LogP:   1.663
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.93
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.511
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   157.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.396 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.836 Fsp3:   0.375
MCE-18:   89.182
?
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:   0.555 Fluc inhibitor:   0.331
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.914
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.78
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.086 Promiscuous compounds:   0.424

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.044 MDCK Permeability:   -5.125
Pgp-inhibitor:   0.778 Pgp-substrate:   0.457
PAMPA:   0.665
?
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):   0.405
20% Bioavailability (F20%):   0.01 30% Bioavailability (F30%):   0.076
50% Bioavailability (F50%):   0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.063
Plasma Protein Binding (PPB):   91.475% Volume Distribution (VD):   0.064
Fu: 9.362%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.991
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.25 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.433 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.937
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.961
?
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):  3.03 Half-life (T1/2):  3.003

ADMET: Toxicity

hERG Blockers:  0.051 hERG Blockers (10um):  0.396
Human Hepatotoxicity (H-HT):  0.443 Drug-induced Liver Injury (DILI):  0.885
AMES Toxicity:  0.664 Rat Oral Acute Toxicity:  0.082
Maximum Recommended Daily Dose:  0.125 Skin Sensitization:  0.702
Carcinogencity:  0.279 Eye Corrosion:  0.001
Eye Irritation:  0.651 Respiratory Toxicity:  0.155
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.589
Hematotoxicity:  0.206 Drug-induced Nephrotoxicity:  0.28
Genotoxicity:  0.222 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.125 Hek293 Cytotoxicity:  0.28
BCF:   0.795
?
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:   3.534
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.728
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.015
?
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
NPO26426 Cassia javanica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26426 Cassia javanica Species Fabaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC495472 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
0.8026 Intermediate Similarity NPC611303
0.8 Intermediate Similarity NPC46420
0.8 Intermediate Similarity NPC271692
0.7867 Intermediate Similarity NPC158674
0.75 Intermediate Similarity NPC249281
0.7108 Intermediate Similarity NPC251417
0.6951 Remote Similarity NPC116458
0.6951 Remote Similarity NPC246943
0.6951 Remote Similarity NPC605784
0.6932 Remote Similarity NPC606657
0.6867 Remote Similarity NPC276377
0.6857 Remote Similarity NPC236769
0.6835 Remote Similarity NPC289667
0.6667 Remote Similarity NPC27640
0.6591 Remote Similarity NPC186816
0.6506 Remote Similarity NPC219904
0.6477 Remote Similarity NPC150164
0.6429 Remote Similarity NPC243930
0.642 Remote Similarity NPC238376
0.6374 Remote Similarity NPC72016
0.6353 Remote Similarity NPC223747
0.6353 Remote Similarity NPC607707
0.6341 Remote Similarity NPC297987
0.6341 Remote Similarity NPC136042
0.6265 Remote Similarity NPC84362
0.622 Remote Similarity NPC108831
0.622 Remote Similarity NPC182634
0.6207 Remote Similarity NPC265115
0.6196 Remote Similarity NPC32641
0.6196 Remote Similarity NPC256188
0.6196 Remote Similarity NPC35119
0.619 Remote Similarity NPC59534
0.6154 Remote Similarity NPC240306
0.6145 Remote Similarity NPC265530
0.6098 Remote Similarity NPC111929
0.6098 Remote Similarity NPC320283
0.6098 Remote Similarity NPC41121
0.6092 Remote Similarity NPC355481
0.6087 Remote Similarity NPC483414
0.6071 Remote Similarity NPC305811
0.6071 Remote Similarity NPC349108
0.6024 Remote Similarity NPC127546
0.6024 Remote Similarity NPC57625
0.6024 Remote Similarity NPC19709
0.6024 Remote Similarity NPC173637
0.6024 Remote Similarity NPC317489
0.6024 Remote Similarity NPC223424
0.6024 Remote Similarity NPC600591
0.5974 Remote Similarity NPC99671
0.5957 Remote Similarity NPC142142
0.5957 Remote Similarity NPC486577
0.5914 Remote Similarity NPC483415
0.5904 Remote Similarity NPC473043
0.5904 Remote Similarity NPC135599
0.5904 Remote Similarity NPC73855
0.5904 Remote Similarity NPC331652
0.5904 Remote Similarity NPC113968
0.5904 Remote Similarity NPC328940
0.5904 Remote Similarity NPC277174
0.5904 Remote Similarity NPC606877
0.5889 Remote Similarity NPC480466
0.5862 Remote Similarity NPC486578
0.5851 Remote Similarity NPC483416
0.5816 Remote Similarity NPC121703
0.5814 Remote Similarity NPC472459
0.5806 Remote Similarity NPC64425
0.5778 Remote Similarity NPC480463
0.5778 Remote Similarity NPC278419
0.5778 Remote Similarity NPC179198
0.5761 Remote Similarity NPC22062
0.5761 Remote Similarity NPC473634
0.5761 Remote Similarity NPC138811
0.5743 Remote Similarity NPC277532
0.5714 Remote Similarity NPC14187
0.57 Remote Similarity NPC477895
0.5698 Remote Similarity NPC181712
0.5684 Remote Similarity NPC209296
0.5684 Remote Similarity NPC473327
0.5652 Remote Similarity NPC267680
0.5644 Remote Similarity NPC480441
0.5644 Remote Similarity NPC25523
0.5625 Remote Similarity NPC5319
0.5616 Remote Similarity NPC262094
0.5591 Remote Similarity NPC293626
0.5581 Remote Similarity NPC64305
0.5581 Remote Similarity NPC95090
0.5581 Remote Similarity NPC27408
0.5579 Remote Similarity NPC470443
0.5568 Remote Similarity NPC285197
0.5568 Remote Similarity NPC488071
0.5567 Remote Similarity NPC476472
0.5567 Remote Similarity NPC294815
0.5567 Remote Similarity NPC16194
0.5556 Remote Similarity NPC488072
0.5541 Remote Similarity NPC76376
0.5529 Remote Similarity NPC160515
0.5517 Remote Similarity NPC24043
0.5506 Remote Similarity NPC22832
0.5506 Remote Similarity NPC120099
0.5506 Remote Similarity NPC21666
0.5484 Remote Similarity NPC67105
0.5474 Remote Similarity NPC153755
0.5463 Remote Similarity NPC175429
0.5402 Remote Similarity NPC277205
0.5402 Remote Similarity NPC37919
0.5395 Remote Similarity NPC176300
0.5395 Remote Similarity NPC270620
0.5395 Remote Similarity NPC166753
0.5393 Remote Similarity NPC175107
0.5385 Remote Similarity NPC203050
0.5385 Remote Similarity NPC225434
0.5385 Remote Similarity NPC601586
0.5376 Remote Similarity NPC609888
0.537 Remote Similarity NPC209550
0.5325 Remote Similarity NPC195202
0.5325 Remote Similarity NPC206604
0.5319 Remote Similarity NPC173582
0.5319 Remote Similarity NPC265885
0.5319 Remote Similarity NPC181465
0.5319 Remote Similarity NPC215710
0.5319 Remote Similarity NPC473438
0.5319 Remote Similarity NPC227508
0.5319 Remote Similarity NPC253788
0.5312 Remote Similarity NPC126784
0.5312 Remote Similarity NPC241423
0.5312 Remote Similarity NPC475366
0.53 Remote Similarity NPC135358
0.5287 Remote Similarity NPC348541
0.5283 Remote Similarity NPC295625
0.5281 Remote Similarity NPC27942
0.5281 Remote Similarity NPC325555
0.5281 Remote Similarity NPC226304
0.5278 Remote Similarity NPC470720
0.5263 Remote Similarity NPC203259
0.5263 Remote Similarity NPC33054
0.5263 Remote Similarity NPC210073
0.5263 Remote Similarity NPC176740
0.5263 Remote Similarity NPC471725
0.5263 Remote Similarity NPC134532
0.5263 Remote Similarity NPC602582
0.5256 Remote Similarity NPC78326
0.5253 Remote Similarity NPC473073
0.5243 Remote Similarity NPC48984
0.5238 Remote Similarity NPC470716
0.5229 Remote Similarity NPC138990
0.5227 Remote Similarity NPC323593
0.5227 Remote Similarity NPC203500
0.5222 Remote Similarity NPC60735
0.5222 Remote Similarity NPC26230
0.5222 Remote Similarity NPC609451
0.5217 Remote Similarity NPC190003
0.5217 Remote Similarity NPC267254
0.5208 Remote Similarity NPC473571
0.5208 Remote Similarity NPC110941
0.52 Remote Similarity NPC103904
0.52 Remote Similarity NPC470445
0.5192 Remote Similarity NPC470715
0.5192 Remote Similarity NPC164704
0.5185 Remote Similarity NPC470719
0.5185 Remote Similarity NPC470717
0.5169 Remote Similarity NPC603655
0.5165 Remote Similarity NPC101026
0.5165 Remote Similarity NPC488077
0.5165 Remote Similarity NPC609478
0.5161 Remote Similarity NPC116864
0.5161 Remote Similarity NPC244776
0.5158 Remote Similarity NPC44931
0.5158 Remote Similarity NPC39834
0.5155 Remote Similarity NPC46202
0.5132 Remote Similarity NPC146679
0.5132 Remote Similarity NPC188871
0.5128 Remote Similarity NPC603596
0.5114 Remote Similarity NPC77672
0.5114 Remote Similarity NPC476405
0.5114 Remote Similarity NPC133671
0.5114 Remote Similarity NPC135391
0.5114 Remote Similarity NPC78263
0.5114 Remote Similarity NPC250069
0.5111 Remote Similarity NPC42773
0.5111 Remote Similarity NPC182045
0.5111 Remote Similarity NPC45522
0.5111 Remote Similarity NPC599850
0.5109 Remote Similarity NPC311830
0.5106 Remote Similarity NPC487212
0.51 Remote Similarity NPC470447
0.51 Remote Similarity NPC475382
0.51 Remote Similarity NPC483412
0.5056 Remote Similarity NPC145038
0.5056 Remote Similarity NPC56077
0.5056 Remote Similarity NPC281131
0.5056 Remote Similarity NPC253662
0.5056 Remote Similarity NPC179950
0.5056 Remote Similarity NPC88789
0.5056 Remote Similarity NPC189142
0.5056 Remote Similarity NPC77660
0.5056 Remote Similarity NPC491374
0.5054 Remote Similarity NPC66087
0.5052 Remote Similarity NPC204693
0.5051 Remote Similarity NPC473623

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC495472 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
0.7222 Intermediate Similarity NPD7808 Phase 3
0.6064 Remote Similarity NPD7251 Phase 2
0.5684 Remote Similarity NPD7054 Phase 4
0.5625 Remote Similarity NPD7804 Clinical (unspecified phase)
0.5263 Remote Similarity NPD6797 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