Natural Product: NPC582594

Natural Product IDNPC582594
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-dihydroxy-5-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-phenyl]-3,5,7-trihydroxy-chromen-4-one
IUPAC Name 2-[3,4-dihydroxy-5-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-phenyl]-3,5,7-trihydroxy-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 KPKDFSLIRPVPJF-MMKWEBTNSA-N
Standard InCHI InChI=1S/C21H20O12/c1-6-14(25)17(28)19(30)21(31-6)33-12-3-7(2-10(24)15(12)26)20-18(29)16(27)13-9(23)4-8(22)5-11(13)32-20/h2-6,14,17,19,21-26,28-30H,1H3/t6-,14-,17+,19-,21-/m0/s1
SMILES C[C@@H]1O[C@@H](OC2=CC(C3=C(O)C(=O)C4=C(O)C=C(O)C=C4O3)=CC(O)=C2O)[C@@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   1.067
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.369
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.01
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   210.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.244 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.172 Fsp3:   0.286
MCE-18:   94.37
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.695 Fluc inhibitor:   0.192
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.93
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.871
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.254 Promiscuous compounds:   0.927

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.333 MDCK Permeability:   -4.888
Pgp-inhibitor:   0.0 Pgp-substrate:   0.209
PAMPA:   0.994
?
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):   0.257
20% Bioavailability (F20%):   0.083 30% Bioavailability (F30%):   0.988
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.095
Plasma Protein Binding (PPB):   87.407% Volume Distribution (VD):   -0.293
Fu: 8.834%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.067

ADMET: Metabolism

CYP1A2-inhibitor:   0.136 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.051
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.219
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.966
?
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):  3.089 Half-life (T1/2):  4.765

ADMET: Toxicity

hERG Blockers:  0.024 hERG Blockers (10um):  0.409
Human Hepatotoxicity (H-HT):  0.32 Drug-induced Liver Injury (DILI):  0.738
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.138
Maximum Recommended Daily Dose:  0.377 Skin Sensitization:  0.864
Carcinogencity:  0.109 Eye Corrosion:  0.001
Eye Irritation:  0.942 Respiratory Toxicity:  0.102
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.779
Hematotoxicity:  0.037 Drug-induced Nephrotoxicity:  0.099
Genotoxicity:  0.832 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.281 Hek293 Cytotoxicity:  0.312
BCF:   0.585
?
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:   3.311
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.569
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.884
?
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
NPO62883 Daviesia flexuosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC582594 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
0.6707 Remote Similarity NPC197285
0.6667 Remote Similarity NPC21100
0.662 Remote Similarity NPC133953
0.6582 Remote Similarity NPC135599
0.6582 Remote Similarity NPC73855
0.6582 Remote Similarity NPC113968
0.6582 Remote Similarity NPC328940
0.6582 Remote Similarity NPC277174
0.6582 Remote Similarity NPC606877
0.65 Remote Similarity NPC127546
0.65 Remote Similarity NPC57625
0.65 Remote Similarity NPC173637
0.65 Remote Similarity NPC317489
0.65 Remote Similarity NPC238376
0.65 Remote Similarity NPC223424
0.65 Remote Similarity NPC600591
0.6322 Remote Similarity NPC187379
0.6296 Remote Similarity NPC254306
0.6235 Remote Similarity NPC223747
0.6173 Remote Similarity NPC111929
0.6173 Remote Similarity NPC320283
0.6173 Remote Similarity NPC41121
0.6098 Remote Similarity NPC108831
0.6098 Remote Similarity NPC182634
0.6024 Remote Similarity NPC265530
0.6 Remote Similarity NPC219904
0.5904 Remote Similarity NPC476405
0.5714 Remote Similarity NPC39834
0.5696 Remote Similarity NPC268668
0.5652 Remote Similarity NPC203259
0.5652 Remote Similarity NPC33054
0.5652 Remote Similarity NPC176740
0.5652 Remote Similarity NPC471725
0.5652 Remote Similarity NPC134532
0.5652 Remote Similarity NPC602582
0.5581 Remote Similarity NPC245014
0.5568 Remote Similarity NPC601710
0.5567 Remote Similarity NPC287889
0.5543 Remote Similarity NPC67105
0.5543 Remote Similarity NPC227508
0.5529 Remote Similarity NPC19388
0.5529 Remote Similarity NPC240431
0.5529 Remote Similarity NPC55786
0.5517 Remote Similarity NPC325555
0.5517 Remote Similarity NPC226304
0.5465 Remote Similarity NPC145038
0.5465 Remote Similarity NPC56077
0.5465 Remote Similarity NPC281131
0.5465 Remote Similarity NPC253662
0.5465 Remote Similarity NPC179950
0.5465 Remote Similarity NPC277205
0.5465 Remote Similarity NPC37919
0.5465 Remote Similarity NPC88789
0.5465 Remote Similarity NPC491374
0.5464 Remote Similarity NPC476472
0.5464 Remote Similarity NPC294815
0.5464 Remote Similarity NPC16194
0.5455 Remote Similarity NPC191306
0.5435 Remote Similarity NPC609888
0.5405 Remote Similarity NPC28274
0.5385 Remote Similarity NPC4390
0.5385 Remote Similarity NPC116864
0.5385 Remote Similarity NPC244776
0.5376 Remote Similarity NPC173582
0.5376 Remote Similarity NPC265885
0.5376 Remote Similarity NPC181465
0.5376 Remote Similarity NPC215710
0.5376 Remote Similarity NPC473438
0.5376 Remote Similarity NPC253788
0.5333 Remote Similarity NPC136761
0.5319 Remote Similarity NPC605592
0.5287 Remote Similarity NPC282987
0.5287 Remote Similarity NPC609879
0.5281 Remote Similarity NPC60735
0.5281 Remote Similarity NPC175107
0.5281 Remote Similarity NPC26230
0.5281 Remote Similarity NPC285197
0.5278 Remote Similarity NPC179271
0.5275 Remote Similarity NPC203050
0.5275 Remote Similarity NPC225434
0.5275 Remote Similarity NPC601586
0.5258 Remote Similarity NPC473327
0.5233 Remote Similarity NPC473043
0.5227 Remote Similarity NPC84265
0.5222 Remote Similarity NPC486578
0.5222 Remote Similarity NPC609478
0.5217 Remote Similarity NPC95866
0.5208 Remote Similarity NPC153755
0.5195 Remote Similarity NPC609179
0.5176 Remote Similarity NPC34531
0.5172 Remote Similarity NPC77672
0.5172 Remote Similarity NPC133671
0.5172 Remote Similarity NPC19709
0.5172 Remote Similarity NPC135391
0.5172 Remote Similarity NPC78263
0.5172 Remote Similarity NPC250069
0.5172 Remote Similarity NPC143851
0.5165 Remote Similarity NPC88023
0.5165 Remote Similarity NPC309025
0.5139 Remote Similarity NPC169749
0.5139 Remote Similarity NPC20791
0.5128 Remote Similarity NPC125062
0.5116 Remote Similarity NPC67037
0.5116 Remote Similarity NPC255615
0.5114 Remote Similarity NPC64305
0.5114 Remote Similarity NPC158674
0.5114 Remote Similarity NPC323593
0.5114 Remote Similarity NPC203500
0.5067 Remote Similarity NPC219330
0.5065 Remote Similarity NPC54394
0.5056 Remote Similarity NPC305811
0.5056 Remote Similarity NPC271692
0.5055 Remote Similarity NPC120099
0.5054 Remote Similarity NPC477848
0.5053 Remote Similarity NPC67326

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC582594 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
0.5652 Remote Similarity NPD6797 Phase 2
0.5139 Remote Similarity NPD1512 Phase 3

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