Natural Product: NPC309025

Natural Product IDNPC309025
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VSFKAJPKOFGJTH-MIUGBVLSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3589341
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

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 VSFKAJPKOFGJTH-MIUGBVLSSA-N
Standard InCHI InChI=1S/C22H22O11/c1-30-13-3-2-9(14-7-12(26)18-11(25)5-10(24)6-16(18)31-14)4-15(13)32-22-21(29)20(28)19(27)17(8-23)33-22/h2-7,17,19-25,27-29H,8H2,1H3/t17-,19-,20+,21-,22-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2cc(ccc2OC)c2cc(=O)c3c(o2)cc(cc3O)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.12 Volume:   430.443
?
Van der Waals volume.
Dense:   1.074 LogP:   1.185
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.512
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.54
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   179.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.302 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.854 Fsp3:   0.318
MCE-18:   86.966
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.61 Fluc inhibitor:   0.321
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.965
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.882
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.106 Promiscuous compounds:   0.627

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.162 MDCK Permeability:   -5.238
Pgp-inhibitor:   0.0 Pgp-substrate:   0.609
PAMPA:   0.861
?
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):   0.488
20% Bioavailability (F20%):   0.203 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.138
Plasma Protein Binding (PPB):   88.582% Volume Distribution (VD):   -0.134
Fu: 9.746%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.931
BSEP inhibitor:   0.012

ADMET: Metabolism

CYP1A2-inhibitor:   0.518 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.101
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.952
HLM stability:   0.123
?
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):  2.64 Half-life (T1/2):  3.438

ADMET: Toxicity

hERG Blockers:  0.022 hERG Blockers (10um):  0.128
Human Hepatotoxicity (H-HT):  0.631 Drug-induced Liver Injury (DILI):  0.954
AMES Toxicity:  0.918 Rat Oral Acute Toxicity:  0.051
Maximum Recommended Daily Dose:  0.209 Skin Sensitization:  0.986
Carcinogencity:  0.519 Eye Corrosion:  0.0
Eye Irritation:  0.824 Respiratory Toxicity:  0.065
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.685
Hematotoxicity:  0.126 Drug-induced Nephrotoxicity:  0.172
Genotoxicity:  0.958 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.33 Hek293 Cytotoxicity:  0.609
BCF:   0.44
?
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:   3.149
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.476
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.699
?
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
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota leaves n.a. n.a. PMID[20634065]
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota flower buds n.a. n.a. PMID[25987378]
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[31727081]
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5227 Lawsonia inermis Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5227 Lawsonia inermis Species Lythraceae 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
NPT1720 Individual protein Plasminogen Homo sapiens Inhibition = 28.5 % PMID[16499316]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -3.6 % PMID[16933872]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT610 Others Molecular identity unknown n.a. Ratio = 1.22 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 0.99 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 1.09 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 0.85 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 1.08 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 0.77 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 0.92 n.a. PMID[25987378]
NPT610 Others Molecular identity unknown n.a. Ratio = 0.93 n.a. PMID[25987378]
NPT2 Others Unspecified n.a. IC50 = 55000.0 nM PMID[18720971]
NPT2 Others Unspecified n.a. Inhibition = 61.5 % PMID[18474575]
NPT2 Others Unspecified n.a. Inhibition = 44.1 % Open TG-GATES in vivo data: Biochemistry
NPT2 Others Unspecified n.a. Inhibition = 40.6 % PMID[20705370]
NPT2 Others Unspecified n.a. Inhibition = 18.0 % PMID[17190465]
NPT2 Others Unspecified n.a. Inhibition = 6.3 % PMID[8254357]

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 NPC309025 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
0.9444 High Similarity NPC88023
0.8108 Intermediate Similarity NPC143851
0.7692 Intermediate Similarity NPC191306
0.7595 Intermediate Similarity NPC243930
0.7595 Intermediate Similarity NPC601710
0.75 Intermediate Similarity NPC607707
0.725 Intermediate Similarity NPC609451
0.6761 Remote Similarity NPC12200
0.6707 Remote Similarity NPC472459
0.6706 Remote Similarity NPC4390
0.6667 Remote Similarity NPC95090
0.6667 Remote Similarity NPC27408
0.6585 Remote Similarity NPC186807
0.6548 Remote Similarity NPC120099
0.6548 Remote Similarity NPC609478
0.6543 Remote Similarity NPC58053
0.6506 Remote Similarity NPC182045
0.6506 Remote Similarity NPC21100
0.6463 Remote Similarity NPC64305
0.6458 Remote Similarity NPC48984
0.6386 Remote Similarity NPC105025
0.6353 Remote Similarity NPC22832
0.6341 Remote Similarity NPC261866
0.631 Remote Similarity NPC325555
0.631 Remote Similarity NPC226304
0.6279 Remote Similarity NPC311830
0.6279 Remote Similarity NPC602805
0.6265 Remote Similarity NPC93337
0.6235 Remote Similarity NPC60735
0.6235 Remote Similarity NPC26230
0.6207 Remote Similarity NPC203050
0.6207 Remote Similarity NPC225434
0.6163 Remote Similarity NPC197285
0.6163 Remote Similarity NPC605067
0.6145 Remote Similarity NPC39360
0.6145 Remote Similarity NPC77672
0.6145 Remote Similarity NPC133671
0.6145 Remote Similarity NPC135391
0.6145 Remote Similarity NPC29763
0.6145 Remote Similarity NPC78263
0.6145 Remote Similarity NPC210003
0.6145 Remote Similarity NPC250069
0.6118 Remote Similarity NPC201292
0.6071 Remote Similarity NPC145038
0.6071 Remote Similarity NPC56077
0.6071 Remote Similarity NPC281131
0.6071 Remote Similarity NPC253662
0.6071 Remote Similarity NPC179950
0.6071 Remote Similarity NPC88789
0.6071 Remote Similarity NPC491374
0.6047 Remote Similarity NPC481043
0.6 Remote Similarity NPC45638
0.5977 Remote Similarity NPC601144
0.5952 Remote Similarity NPC19388
0.5952 Remote Similarity NPC240431
0.5952 Remote Similarity NPC55786
0.593 Remote Similarity NPC222936
0.5882 Remote Similarity NPC189142
0.5882 Remote Similarity NPC77660
0.5844 Remote Similarity NPC605634
0.5765 Remote Similarity NPC254306
0.5765 Remote Similarity NPC83283
0.573 Remote Similarity NPC165970
0.5698 Remote Similarity NPC146792
0.5698 Remote Similarity NPC156457
0.5679 Remote Similarity NPC183
0.5676 Remote Similarity NPC231772
0.5676 Remote Similarity NPC62536
0.567 Remote Similarity NPC477629
0.5667 Remote Similarity NPC288131
0.5652 Remote Similarity NPC113163
0.5652 Remote Similarity NPC603300
0.5632 Remote Similarity NPC181712
0.5632 Remote Similarity NPC610763
0.5618 Remote Similarity NPC284960
0.5591 Remote Similarity NPC66618
0.5591 Remote Similarity NPC305987
0.5581 Remote Similarity NPC110349
0.5581 Remote Similarity NPC45618
0.5568 Remote Similarity NPC138540
0.5556 Remote Similarity NPC136761
0.5521 Remote Similarity NPC477628
0.5506 Remote Similarity NPC219904
0.5488 Remote Similarity NPC78697
0.5465 Remote Similarity NPC63454
0.5465 Remote Similarity NPC183851
0.5455 Remote Similarity NPC58716
0.5455 Remote Similarity NPC52005
0.5455 Remote Similarity NPC606638
0.5444 Remote Similarity NPC486578
0.5412 Remote Similarity NPC288084
0.5402 Remote Similarity NPC112755
0.5402 Remote Similarity NPC170675
0.5393 Remote Similarity NPC27942
0.5393 Remote Similarity NPC117260
0.5385 Remote Similarity NPC183950
0.5354 Remote Similarity NPC76831
0.5349 Remote Similarity NPC67037
0.5349 Remote Similarity NPC255615
0.5341 Remote Similarity NPC168822
0.5341 Remote Similarity NPC259152
0.534 Remote Similarity NPC477895
0.5333 Remote Similarity NPC175107
0.5306 Remote Similarity NPC124155
0.53 Remote Similarity NPC287889
0.5288 Remote Similarity NPC470712
0.5281 Remote Similarity NPC488080
0.5281 Remote Similarity NPC169977
0.5275 Remote Similarity NPC21666
0.5269 Remote Similarity NPC600989
0.5263 Remote Similarity NPC120464
0.5263 Remote Similarity NPC483773
0.5263 Remote Similarity NPC601901
0.5233 Remote Similarity NPC34531
0.5222 Remote Similarity NPC198324
0.5217 Remote Similarity NPC223747
0.5217 Remote Similarity NPC172202
0.5217 Remote Similarity NPC284127
0.5208 Remote Similarity NPC156869
0.52 Remote Similarity NPC256760
0.52 Remote Similarity NPC475382
0.5195 Remote Similarity NPC600900
0.5189 Remote Similarity NPC470718
0.5185 Remote Similarity NPC470713
0.5169 Remote Similarity NPC282987
0.5169 Remote Similarity NPC265530
0.5169 Remote Similarity NPC323593
0.5169 Remote Similarity NPC203500
0.5165 Remote Similarity NPC285197
0.5161 Remote Similarity NPC170052
0.5161 Remote Similarity NPC135846
0.5161 Remote Similarity NPC601586
0.5158 Remote Similarity NPC29958
0.5158 Remote Similarity NPC139320
0.5128 Remote Similarity NPC159103
0.5128 Remote Similarity NPC255350
0.5114 Remote Similarity NPC111929
0.5114 Remote Similarity NPC320283
0.5114 Remote Similarity NPC331652
0.5114 Remote Similarity NPC41121
0.5111 Remote Similarity NPC24043
0.5111 Remote Similarity NPC472385
0.5111 Remote Similarity NPC603655
0.5109 Remote Similarity NPC101026
0.5109 Remote Similarity NPC101731
0.5109 Remote Similarity NPC80188
0.5109 Remote Similarity NPC488077
0.5106 Remote Similarity NPC254855
0.5106 Remote Similarity NPC94610
0.5106 Remote Similarity NPC211594
0.5104 Remote Similarity NPC471748
0.5063 Remote Similarity NPC195202
0.5063 Remote Similarity NPC603596
0.5056 Remote Similarity NPC289667
0.5056 Remote Similarity NPC127546
0.5056 Remote Similarity NPC57625
0.5056 Remote Similarity NPC173637
0.5056 Remote Similarity NPC317489
0.5056 Remote Similarity NPC223424
0.5056 Remote Similarity NPC600591
0.5055 Remote Similarity NPC42773
0.5055 Remote Similarity NPC45522
0.5055 Remote Similarity NPC599850
0.5054 Remote Similarity NPC206123
0.5053 Remote Similarity NPC84324
0.5053 Remote Similarity NPC8856
0.5053 Remote Similarity NPC472607
0.5052 Remote Similarity NPC476410
0.505 Remote Similarity NPC195257
0.5048 Remote Similarity NPC219043

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC309025 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
0.5128 Remote Similarity NPD2801 Pre-clinical

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