Natural Product: NPC111440

Natural Product IDNPC111440
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PFTAWBLQPZVEMU-WUJWULDRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12309507
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003012] Flavan-3-ols
            • [CHEMONTID:0001584] Catechins

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 PFTAWBLQPZVEMU-WUJWULDRSA-N
Standard InCHI InChI=1S/C15H14O6/c16-8-4-11(18)9-6-13(20)15(21-14(9)5-8)7-1-2-10(17)12(19)3-7/h1-5,13,15-20H,6H2/t13?,15-/m0/s1
SMILES c1cc(c(cc1[C@H]1C(Cc2c(cc(cc2O1)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.08 Volume:   279.249
?
Van der Waals volume.
Dense:   1.039 LogP:   0.718
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.111
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.22
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   110.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.51 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.344 Fsp3:   0.2
MCE-18:   60.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.661 Fluc inhibitor:   0.495
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.19
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.18
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.469 Promiscuous compounds:   0.493

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.173 MDCK Permeability:   -4.946
Pgp-inhibitor:   0.0 Pgp-substrate:   0.055
PAMPA:   0.482
?
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):   0.006
20% Bioavailability (F20%):   0.719 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.819
Plasma Protein Binding (PPB):   93.549% Volume Distribution (VD):   0.075
Fu: 11.079%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.706
OATP1B3 inhibitor:   0.911 BCRP inhibitor:   0.063
BSEP inhibitor:   0.027

ADMET: Metabolism

CYP1A2-inhibitor:   0.064 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.401 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.903 CYP2D6-substrate:   0.043
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.119
HLM stability:   0.035
?
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):  14.369 Half-life (T1/2):  2.175

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.766
Human Hepatotoxicity (H-HT):  0.664 Drug-induced Liver Injury (DILI):  0.07
AMES Toxicity:  0.517 Rat Oral Acute Toxicity:  0.513
Maximum Recommended Daily Dose:  0.755 Skin Sensitization:  0.901
Carcinogencity:  0.206 Eye Corrosion:  0.003
Eye Irritation:  0.978 Respiratory Toxicity:  0.316
Drug-induced Neurotoxicity:  0.092 Ototoxicity:  0.783
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.064
Genotoxicity:  0.897 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.701 Hek293 Cytotoxicity:  0.695
BCF:   0.889
?
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:   3.237
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.598
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.063
?
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
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. root n.a. PMID[16564530]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[29359942]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[31944695]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots; Tubers n.a. n.a. PMID[7714535]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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 NPC111440 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
1.0 High Similarity NPC261619
1.0 High Similarity NPC61477
1.0 High Similarity NPC78770
1.0 High Similarity NPC219876
1.0 High Similarity NPC126029
1.0 High Similarity NPC15658
0.8222 Intermediate Similarity NPC207179
0.8222 Intermediate Similarity NPC167571
0.8222 Intermediate Similarity NPC278552
0.7826 Intermediate Similarity NPC268266
0.7826 Intermediate Similarity NPC42760
0.7826 Intermediate Similarity NPC220825
0.7826 Intermediate Similarity NPC268342
0.7241 Intermediate Similarity NPC28440
0.7115 Intermediate Similarity NPC16435
0.7115 Intermediate Similarity NPC171932
0.7018 Intermediate Similarity NPC58190
0.7018 Intermediate Similarity NPC108811
0.7018 Intermediate Similarity NPC170103
0.7018 Intermediate Similarity NPC236202
0.7018 Intermediate Similarity NPC262911
0.7018 Intermediate Similarity NPC202742
0.6897 Remote Similarity NPC246202
0.6897 Remote Similarity NPC224161
0.6897 Remote Similarity NPC46335
0.6897 Remote Similarity NPC294558
0.6897 Remote Similarity NPC18185
0.6897 Remote Similarity NPC263940
0.6897 Remote Similarity NPC279406
0.6897 Remote Similarity NPC486519
0.6875 Remote Similarity NPC601844
0.68 Remote Similarity NPC47398
0.68 Remote Similarity NPC234333
0.68 Remote Similarity NPC260898
0.6731 Remote Similarity NPC61946
0.6415 Remote Similarity NPC36835
0.6415 Remote Similarity NPC246162
0.6415 Remote Similarity NPC9743
0.6415 Remote Similarity NPC260491
0.6415 Remote Similarity NPC61506
0.6415 Remote Similarity NPC240476
0.6349 Remote Similarity NPC226809
0.625 Remote Similarity NPC150670
0.6182 Remote Similarity NPC178054
0.6167 Remote Similarity NPC82917
0.6167 Remote Similarity NPC9636
0.6154 Remote Similarity NPC278548
0.6129 Remote Similarity NPC313116
0.6129 Remote Similarity NPC308402
0.6129 Remote Similarity NPC603340
0.5938 Remote Similarity NPC70409
0.5938 Remote Similarity NPC204770
0.5938 Remote Similarity NPC600551
0.5938 Remote Similarity NPC601980
0.5938 Remote Similarity NPC602065
0.5938 Remote Similarity NPC611024
0.5909 Remote Similarity NPC302549
0.5902 Remote Similarity NPC469313
0.5758 Remote Similarity NPC272552
0.5758 Remote Similarity NPC226108
0.5758 Remote Similarity NPC322899
0.5758 Remote Similarity NPC600630
0.5758 Remote Similarity NPC607896
0.5758 Remote Similarity NPC611369
0.5738 Remote Similarity NPC289990
0.5735 Remote Similarity NPC20050
0.5692 Remote Similarity NPC470802
0.5672 Remote Similarity NPC46283
0.5672 Remote Similarity NPC469944
0.5652 Remote Similarity NPC306267
0.5645 Remote Similarity NPC607430
0.5588 Remote Similarity NPC44192
0.5577 Remote Similarity NPC482472
0.5574 Remote Similarity NPC96576
0.5571 Remote Similarity NPC135021
0.5556 Remote Similarity NPC20757
0.5556 Remote Similarity NPC227516
0.5469 Remote Similarity NPC184245
0.5469 Remote Similarity NPC187801
0.5469 Remote Similarity NPC610920
0.5455 Remote Similarity NPC246328
0.5455 Remote Similarity NPC27532
0.5429 Remote Similarity NPC478616
0.5429 Remote Similarity NPC478339
0.541 Remote Similarity NPC474656
0.541 Remote Similarity NPC38779
0.541 Remote Similarity NPC114179
0.541 Remote Similarity NPC68324
0.541 Remote Similarity NPC289322
0.541 Remote Similarity NPC160512
0.5405 Remote Similarity NPC86630
0.5397 Remote Similarity NPC277331
0.5397 Remote Similarity NPC100482
0.5342 Remote Similarity NPC147743
0.5342 Remote Similarity NPC4809
0.5342 Remote Similarity NPC73517
0.5333 Remote Similarity NPC106601
0.5333 Remote Similarity NPC151474
0.5333 Remote Similarity NPC478340
0.5263 Remote Similarity NPC212614
0.5263 Remote Similarity NPC205613
0.5217 Remote Similarity NPC134911
0.5156 Remote Similarity NPC601196
0.5156 Remote Similarity NPC601999
0.5147 Remote Similarity NPC211561
0.5147 Remote Similarity NPC601997
0.5147 Remote Similarity NPC609211
0.5147 Remote Similarity NPC610665
0.5132 Remote Similarity NPC78074
0.5088 Remote Similarity NPC321011
0.5088 Remote Similarity NPC294852
0.5088 Remote Similarity NPC188679
0.5085 Remote Similarity NPC471744
0.5063 Remote Similarity NPC159526

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC111440 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
1.0 High Similarity NPD1612 Clinical (unspecified phase)
1.0 High Similarity NPD1613 Phase 4

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