Natural Product: NPC473043

Natural Product IDNPC473043
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PAVGTJUTHHTYIM-HFBJJCSWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3604315
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 PAVGTJUTHHTYIM-HFBJJCSWSA-N
Standard InCHI InChI=1S/C21H20O11/c1-7-17(26)19(28)20(29)21(30-7)31-9-4-10(22)16-11(23)6-14(32-15(16)5-9)8-2-12(24)18(27)13(25)3-8/h2-7,17,19-22,24-29H,1H3/t7-,17-,19+,20+,21-/m0/s1
SMILES CC1C(C(C(C(O1)OC2=CC(=C3C(=C2)OC(=CC3=O)C4=CC(=C(C(=C4)O)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.1 Volume:   413.147
?
Van der Waals volume.
Dense:   1.085 LogP:   0.338
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.82
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.794
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   190.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.276 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.073 Fsp3:   0.286
MCE-18:   91.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.628 Fluc inhibitor:   0.02
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.988
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.883
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.26 Promiscuous compounds:   0.903

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.132 MDCK Permeability:   -5.058
Pgp-inhibitor:   0.0 Pgp-substrate:   0.687
PAMPA:   0.998
?
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):   0.705
20% Bioavailability (F20%):   0.947 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.971
Plasma Protein Binding (PPB):   81.106% Volume Distribution (VD):   -0.005
Fu: 18.471%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.438
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.971
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.225
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.478
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.004
?
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):  3.884 Half-life (T1/2):  3.403

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.742
Human Hepatotoxicity (H-HT):  0.364 Drug-induced Liver Injury (DILI):  0.961
AMES Toxicity:  0.784 Rat Oral Acute Toxicity:  0.413
Maximum Recommended Daily Dose:  0.752 Skin Sensitization:  0.979
Carcinogencity:  0.268 Eye Corrosion:  0.0
Eye Irritation:  0.805 Respiratory Toxicity:  0.25
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.949
Hematotoxicity:  0.009 Drug-induced Nephrotoxicity:  0.004
Genotoxicity:  0.977 RPMI-8226 Immunitoxicity:  0.012
A549 Cytotoxicity:  0.935 Hek293 Cytotoxicity:  0.621
BCF:   0.411
?
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:   3.056
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.834
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.769
?
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
NPO5755.1 Bauhinia glauca Under-species n.a. n.a. n.a. n.a. n.a. PMID[26096681]

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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 41.28 % PMID[26096681]

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 NPC473043 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
0.8676 High Similarity NPC19709
0.8 Intermediate Similarity NPC331652
0.7297 Intermediate Similarity NPC158674
0.7297 Intermediate Similarity NPC189142
0.7297 Intermediate Similarity NPC77660
0.7162 Intermediate Similarity NPC261866
0.716 Intermediate Similarity NPC210073
0.6962 Remote Similarity NPC190003
0.6933 Remote Similarity NPC238376
0.6711 Remote Similarity NPC39360
0.6711 Remote Similarity NPC29763
0.6711 Remote Similarity NPC210003
0.6627 Remote Similarity NPC44931
0.6623 Remote Similarity NPC95090
0.6623 Remote Similarity NPC27408
0.6548 Remote Similarity NPC22062
0.6548 Remote Similarity NPC473634
0.6548 Remote Similarity NPC138811
0.6538 Remote Similarity NPC271692
0.6538 Remote Similarity NPC181712
0.65 Remote Similarity NPC22832
0.6494 Remote Similarity NPC249281
0.6471 Remote Similarity NPC115674
0.6456 Remote Similarity NPC27942
0.6437 Remote Similarity NPC209296
0.6429 Remote Similarity NPC227508
0.642 Remote Similarity NPC605784
0.6296 Remote Similarity NPC243930
0.6296 Remote Similarity NPC601144
0.6282 Remote Similarity NPC108831
0.6282 Remote Similarity NPC182634
0.622 Remote Similarity NPC311830
0.622 Remote Similarity NPC607707
0.6173 Remote Similarity NPC611303
0.6136 Remote Similarity NPC65711
0.6125 Remote Similarity NPC46420
0.6125 Remote Similarity NPC349108
0.6067 Remote Similarity NPC229409
0.6024 Remote Similarity NPC116458
0.6024 Remote Similarity NPC246943
0.6 Remote Similarity NPC8856
0.5977 Remote Similarity NPC65003
0.5976 Remote Similarity NPC20505
0.5952 Remote Similarity NPC276377
0.5949 Remote Similarity NPC135599
0.5949 Remote Similarity NPC73855
0.5949 Remote Similarity NPC113968
0.5949 Remote Similarity NPC328940
0.5949 Remote Similarity NPC277174
0.5949 Remote Similarity NPC606877
0.5934 Remote Similarity NPC475382
0.5862 Remote Similarity NPC67105
0.5814 Remote Similarity NPC251417
0.5802 Remote Similarity NPC277205
0.5802 Remote Similarity NPC37919
0.5802 Remote Similarity NPC136042
0.5732 Remote Similarity NPC84362
0.5714 Remote Similarity NPC473623
0.5699 Remote Similarity NPC101636
0.5699 Remote Similarity NPC298171
0.5682 Remote Similarity NPC275454
0.5667 Remote Similarity NPC46202
0.5667 Remote Similarity NPC64051
0.5663 Remote Similarity NPC201292
0.5652 Remote Similarity NPC488089
0.5618 Remote Similarity NPC150164
0.5595 Remote Similarity NPC282169
0.5591 Remote Similarity NPC195257
0.5581 Remote Similarity NPC355481
0.5556 Remote Similarity NPC186816
0.5556 Remote Similarity NPC160515
0.5542 Remote Similarity NPC58716
0.5542 Remote Similarity NPC45638
0.5529 Remote Similarity NPC608742
0.5493 Remote Similarity NPC108406
0.5488 Remote Similarity NPC289667
0.5488 Remote Similarity NPC348541
0.5484 Remote Similarity NPC270675
0.5484 Remote Similarity NPC195685
0.5476 Remote Similarity NPC59534
0.5455 Remote Similarity NPC480463
0.5455 Remote Similarity NPC606546
0.5422 Remote Similarity NPC297987
0.5422 Remote Similarity NPC168822
0.5385 Remote Similarity NPC204693
0.5376 Remote Similarity NPC32641
0.5376 Remote Similarity NPC256188
0.5376 Remote Similarity NPC72016
0.5376 Remote Similarity NPC35119
0.5376 Remote Similarity NPC606657
0.5361 Remote Similarity NPC11468
0.5357 Remote Similarity NPC186807
0.5357 Remote Similarity NPC27640
0.5349 Remote Similarity NPC80188
0.5316 Remote Similarity NPC134819
0.5312 Remote Similarity NPC484301
0.5312 Remote Similarity NPC472994
0.5301 Remote Similarity NPC127546
0.5301 Remote Similarity NPC58053
0.5301 Remote Similarity NPC57625
0.5301 Remote Similarity NPC173637
0.5301 Remote Similarity NPC317489
0.5301 Remote Similarity NPC223424
0.5301 Remote Similarity NPC143851
0.5301 Remote Similarity NPC600591
0.5287 Remote Similarity NPC220169
0.5281 Remote Similarity NPC254540
0.5258 Remote Similarity NPC14187
0.5238 Remote Similarity NPC323593
0.5238 Remote Similarity NPC203500
0.5233 Remote Similarity NPC285197
0.52 Remote Similarity NPC473644
0.519 Remote Similarity NPC191154
0.5176 Remote Similarity NPC105025
0.5169 Remote Similarity NPC211594
0.5155 Remote Similarity NPC253685
0.5149 Remote Similarity NPC311850
0.5135 Remote Similarity NPC177298
0.5119 Remote Similarity NPC45618
0.51 Remote Similarity NPC472993
0.5096 Remote Similarity NPC198199
0.5059 Remote Similarity NPC93337
0.5059 Remote Similarity NPC146792
0.5057 Remote Similarity NPC191306
0.5057 Remote Similarity NPC609451
0.5053 Remote Similarity NPC150767
0.505 Remote Similarity NPC480441

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473043 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
0.6437 Remote Similarity NPD7054 Phase 4
0.5263 Remote Similarity NPD7251 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