Natural Product: NPC183851

Natural Product IDNPC183851
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(7''r,8''s)-4'',5,7-Trihydroxy-3',5'-Dimethoxy-4',8''-Oxyflavonolignan-7'',9''-Diol
IUPAC Name 2-[4-[(1R,2S)-1,3-dihydroxy-1-(4-hydroxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-5,7-dihydroxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1797780
PubChem CID 53354811
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002595] 3'-O-methylated flavonoids

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 XWGDMVNWFZRSNF-UKILVPOCSA-N
Standard InCHI InChI=1S/C26H24O10/c1-33-21-7-14(19-11-18(31)24-17(30)9-16(29)10-20(24)35-19)8-22(34-2)26(21)36-23(12-27)25(32)13-3-5-15(28)6-4-13/h3-11,23,25,27-30,32H,12H2,1-2H3/t23-,25+/m0/s1
SMILES COc1cc(cc(c1O[C@@H](CO)[C@@H](c1ccc(cc1)O)O)OC)c1cc(=O)c2c(cc(cc2o1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   496.14 Volume:   482.927
?
Van der Waals volume.
Dense:   1.027 LogP:   1.906
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.119
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.245
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   24.0
TPSA:   159.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.245 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.537 Fsp3:   0.192
MCE-18:   52.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.582 Fluc inhibitor:   0.514
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.93
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.805
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.118 Promiscuous compounds:   0.759

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.143 MDCK Permeability:   -4.909
Pgp-inhibitor:   0.016 Pgp-substrate:   0.233
PAMPA:   0.637
?
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):   0.0
20% Bioavailability (F20%):   0.065 30% Bioavailability (F30%):   0.624
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.467
Plasma Protein Binding (PPB):   93.8% Volume Distribution (VD):   0.188
Fu: 6.723%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.985
BSEP inhibitor:   0.487

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.095 CYP2C9-substrate:   0.322
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.981
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.161
HLM stability:   0.342
?
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):  4.798 Half-life (T1/2):  1.806

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.278
Human Hepatotoxicity (H-HT):  0.786 Drug-induced Liver Injury (DILI):  0.436
AMES Toxicity:  0.517 Rat Oral Acute Toxicity:  0.254
Maximum Recommended Daily Dose:  0.53 Skin Sensitization:  0.971
Carcinogencity:  0.396 Eye Corrosion:  0.006
Eye Irritation:  0.977 Respiratory Toxicity:  0.328
Drug-induced Neurotoxicity:  0.154 Ototoxicity:  0.276
Hematotoxicity:  0.031 Drug-induced Nephrotoxicity:  0.043
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.664 Hek293 Cytotoxicity:  0.842
BCF:   0.865
?
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:   3.581
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.55
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.858
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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
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. stem n.a. PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. skin-removed stems Pingle Town, Sichuang Province, China 2008-AUG PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. PMID[22690646]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19192 Sinocalamus affinis Species n.a. n.a. 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
NPT681 Cell line PC-12 Rattus norvegicus Activity = 80.7 % PMID[21469695]
NPT2 Others Unspecified n.a. Inhibition < 30.0 % PMID[21469695]

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 NPC183851 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 NPC63454
0.8732 High Similarity NPC172202
0.8732 High Similarity NPC284127
0.7031 Intermediate Similarity NPC62536
0.6585 Remote Similarity NPC84324
0.65 Remote Similarity NPC101731
0.6353 Remote Similarity NPC476410
0.6029 Remote Similarity NPC120464
0.6029 Remote Similarity NPC483773
0.6 Remote Similarity NPC12200
0.6 Remote Similarity NPC606638
0.5942 Remote Similarity NPC600900
0.5747 Remote Similarity NPC113163
0.5694 Remote Similarity NPC183950
0.5682 Remote Similarity NPC66618
0.5682 Remote Similarity NPC305987
0.5647 Remote Similarity NPC165970
0.5581 Remote Similarity NPC288131
0.5571 Remote Similarity NPC231772
0.5571 Remote Similarity NPC601901
0.5465 Remote Similarity NPC88023
0.5465 Remote Similarity NPC309025
0.5385 Remote Similarity NPC183
0.5373 Remote Similarity NPC50898
0.5342 Remote Similarity NPC52005
0.5333 Remote Similarity NPC605634
0.5211 Remote Similarity NPC219330
0.5181 Remote Similarity NPC272064
0.5139 Remote Similarity NPC33265
0.5139 Remote Similarity NPC610359
0.507 Remote Similarity NPC75279
0.506 Remote Similarity NPC290830
0.506 Remote Similarity NPC71061

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC183851 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