Natural Product: NPC218017

Natural Product IDNPC218017
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SJXSFDSZZXJLFJ-CZTZGLBASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101876630
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003531] Flavonoid-3-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 SJXSFDSZZXJLFJ-CZTZGLBASA-N
Standard InCHI InChI=1S/C21H20O11/c22-7-11-14(25)17(28)18(29)21(31-11)32-20-16(27)12-10(6-9(23)13(24)15(12)26)30-19(20)8-4-2-1-3-5-8/h1-6,11,14,17-18,21-26,28-29H,7H2/t11-,14-,17+,18-,21+/m1/s1
SMILES c1ccc(cc1)c1c(c(=O)c2c(cc(c(c2O)O)O)o1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.1 Volume:   413.147
?
Van der Waals volume.
Dense:   1.085 LogP:   0.964
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.455
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.557
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 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:   0.261 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.889 Fsp3:   0.286
MCE-18:   87.63
?
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:   0.618 Fluc inhibitor:   0.275
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.803
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.476
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.229 Promiscuous compounds:   0.702

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.294 MDCK Permeability:   -5.16
Pgp-inhibitor:   0.026 Pgp-substrate:   0.049
PAMPA:   0.971
?
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):   0.059
20% Bioavailability (F20%):   0.012 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.223
Plasma Protein Binding (PPB):   89.288% Volume Distribution (VD):   -0.234
Fu: 7.241%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.834
BSEP inhibitor:   0.145

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.034
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.989
HLM stability:   0.532
?
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):  3.341 Half-life (T1/2):  3.236

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.288
Human Hepatotoxicity (H-HT):  0.625 Drug-induced Liver Injury (DILI):  0.97
AMES Toxicity:  0.858 Rat Oral Acute Toxicity:  0.038
Maximum Recommended Daily Dose:  0.141 Skin Sensitization:  1.0
Carcinogencity:  0.217 Eye Corrosion:  0.0
Eye Irritation:  0.666 Respiratory Toxicity:  0.019
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.941
Hematotoxicity:  0.056 Drug-induced Nephrotoxicity:  0.065
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.01
A549 Cytotoxicity:  0.813 Hek293 Cytotoxicity:  0.235
BCF:   0.532
?
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:   3.18
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.491
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.823
?
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
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[19948405]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. seed n.a. PMID[23672042]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[36483735]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28574 Oroxylum indicum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28574 Oroxylum indicum Species Bignoniaceae 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 NPC218017 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
0.6842 Remote Similarity NPC19388
0.6842 Remote Similarity NPC240431
0.6842 Remote Similarity NPC77672
0.6842 Remote Similarity NPC55786
0.6842 Remote Similarity NPC133671
0.6842 Remote Similarity NPC135391
0.6842 Remote Similarity NPC78263
0.6842 Remote Similarity NPC250069
0.6753 Remote Similarity NPC145038
0.6753 Remote Similarity NPC56077
0.6753 Remote Similarity NPC281131
0.6753 Remote Similarity NPC64305
0.6753 Remote Similarity NPC253662
0.6753 Remote Similarity NPC179950
0.6753 Remote Similarity NPC88789
0.6753 Remote Similarity NPC491374
0.6667 Remote Similarity NPC488080
0.6667 Remote Similarity NPC169977
0.6582 Remote Similarity NPC42773
0.6582 Remote Similarity NPC472459
0.6582 Remote Similarity NPC45522
0.641 Remote Similarity NPC289667
0.6329 Remote Similarity NPC297987
0.6329 Remote Similarity NPC136042
0.6296 Remote Similarity NPC60735
0.6296 Remote Similarity NPC26230
0.6279 Remote Similarity NPC65563
0.6279 Remote Similarity NPC470949
0.625 Remote Similarity NPC24043
0.622 Remote Similarity NPC101026
0.622 Remote Similarity NPC120099
0.622 Remote Similarity NPC488077
0.6173 Remote Similarity NPC325555
0.6173 Remote Similarity NPC226304
0.6098 Remote Similarity NPC488071
0.6071 Remote Similarity NPC203050
0.6071 Remote Similarity NPC225434
0.6026 Remote Similarity NPC288084
0.6026 Remote Similarity NPC34531
0.5976 Remote Similarity NPC599850
0.5952 Remote Similarity NPC116458
0.5952 Remote Similarity NPC246943
0.5952 Remote Similarity NPC605784
0.5949 Remote Similarity NPC67037
0.5949 Remote Similarity NPC255615
0.5926 Remote Similarity NPC8573
0.5854 Remote Similarity NPC84362
0.5833 Remote Similarity NPC609478
0.5802 Remote Similarity NPC45618
0.573 Remote Similarity NPC156869
0.5698 Remote Similarity NPC488072
0.5682 Remote Similarity NPC29958
0.5682 Remote Similarity NPC139320
0.5679 Remote Similarity NPC111929
0.5679 Remote Similarity NPC320283
0.5679 Remote Similarity NPC135599
0.5679 Remote Similarity NPC73855
0.5679 Remote Similarity NPC41121
0.5679 Remote Similarity NPC113968
0.5679 Remote Similarity NPC328940
0.5679 Remote Similarity NPC277174
0.5679 Remote Similarity NPC606877
0.5647 Remote Similarity NPC604599
0.5618 Remote Similarity NPC471748
0.561 Remote Similarity NPC127546
0.561 Remote Similarity NPC57625
0.561 Remote Similarity NPC173637
0.561 Remote Similarity NPC317489
0.561 Remote Similarity NPC223424
0.561 Remote Similarity NPC600591
0.5604 Remote Similarity NPC488073
0.5581 Remote Similarity NPC206123
0.5568 Remote Similarity NPC251417
0.5529 Remote Similarity NPC168584
0.5476 Remote Similarity NPC305811
0.5476 Remote Similarity NPC603655
0.5465 Remote Similarity NPC148710
0.5465 Remote Similarity NPC21666
0.5393 Remote Similarity NPC480463
0.5368 Remote Similarity NPC76831
0.5349 Remote Similarity NPC175107
0.5341 Remote Similarity NPC170052
0.5341 Remote Similarity NPC135846
0.5333 Remote Similarity NPC480466
0.5294 Remote Similarity NPC245014
0.5281 Remote Similarity NPC254855
0.5281 Remote Similarity NPC94610
0.5269 Remote Similarity NPC64425
0.5238 Remote Similarity NPC249281
0.5238 Remote Similarity NPC143851
0.5176 Remote Similarity NPC265530
0.5176 Remote Similarity NPC277205
0.5176 Remote Similarity NPC158674
0.5176 Remote Similarity NPC37919
0.5172 Remote Similarity NPC219904
0.5116 Remote Similarity NPC58716
0.5116 Remote Similarity NPC46420
0.5116 Remote Similarity NPC84265
0.5116 Remote Similarity NPC271692
0.5116 Remote Similarity NPC27640
0.5111 Remote Similarity NPC116864
0.5111 Remote Similarity NPC244776
0.5109 Remote Similarity NPC470405
0.51 Remote Similarity NPC189564
0.5068 Remote Similarity NPC214138
0.5057 Remote Similarity NPC21100
0.5057 Remote Similarity NPC117260
0.5056 Remote Similarity NPC223747
0.5054 Remote Similarity NPC605592
0.505 Remote Similarity NPC292019
0.505 Remote Similarity NPC202908

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC218017 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