Natural Product: NPC293701

Natural Product IDNPC293701
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chushizisins D
IUPAC Name (1S,2R)-1-(4-hydroxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propane-1,3-diol
Synonyms chushizisins D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL550571
PubChem CID 45269748
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 KMRAGNBQNZWMMG-MOPGFXCFSA-N
Standard InCHI InChI=1S/C19H24O6/c1-24-17-11-13(3-2-10-20)4-9-16(17)25-18(12-21)19(23)14-5-7-15(22)8-6-14/h4-9,11,18-23H,2-3,10,12H2,1H3/t18-,19+/m1/s1
SMILES COc1cc(CCCO)ccc1O[C@H](CO)[C@H](c1ccc(cc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.16 Volume:   356.99
?
Van der Waals volume.
Dense:   0.975 LogP:   1.021
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.329
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.847
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   12.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.551 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.984 Fsp3:   0.368
MCE-18:   26.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.512 Fluc inhibitor:   0.363
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.186
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.116 Promiscuous compounds:   0.23

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.039 MDCK Permeability:   -4.761
Pgp-inhibitor:   0.017 Pgp-substrate:   0.473
PAMPA:   0.838
?
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):   0.002
20% Bioavailability (F20%):   0.159 30% Bioavailability (F30%):   0.491
50% Bioavailability (F50%):   0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.299
Plasma Protein Binding (PPB):   69.829% Volume Distribution (VD):   0.071
Fu: 28.206%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.756
OATP1B3 inhibitor:   0.907 BCRP inhibitor:   0.124
BSEP inhibitor:   0.464

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.092 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.807
HLM stability:   0.002
?
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):  8.048 Half-life (T1/2):  1.677

ADMET: Toxicity

hERG Blockers:  0.196 hERG Blockers (10um):  0.386
Human Hepatotoxicity (H-HT):  0.76 Drug-induced Liver Injury (DILI):  0.088
AMES Toxicity:  0.245 Rat Oral Acute Toxicity:  0.016
Maximum Recommended Daily Dose:  0.129 Skin Sensitization:  0.883
Carcinogencity:  0.146 Eye Corrosion:  0.0
Eye Irritation:  0.677 Respiratory Toxicity:  0.035
Drug-induced Neurotoxicity:  0.372 Ototoxicity:  0.939
Hematotoxicity:  0.095 Drug-induced Nephrotoxicity:  0.709
Genotoxicity:  0.127 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.33 Hek293 Cytotoxicity:  0.663
BCF:   0.377
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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:   2.798
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.26
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.374
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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
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. root n.a. PMID[11395279]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants Shawnee National Forest, Harrisburg, IL, US n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants n.a. n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[12419367]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota leaves Kaohsiung, Taiwan 2006-SEP PMID[18986201]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota Fruits n.a. n.a. PMID[19296617]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358644]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5495 Broussonetia papyrifera Species Moraceae 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
NPT1 Others Radical scavenging activity n.a. IC50 = 273900.0 nM PMID[21807513]

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 NPC293701 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
0.7963 Intermediate Similarity NPC111247
0.7963 Intermediate Similarity NPC292056
0.6379 Remote Similarity NPC114901
0.6379 Remote Similarity NPC48990
0.6207 Remote Similarity NPC469613
0.6207 Remote Similarity NPC30043
0.6207 Remote Similarity NPC469625
0.6167 Remote Similarity NPC163332
0.6102 Remote Similarity NPC16208
0.5965 Remote Similarity NPC3439
0.5965 Remote Similarity NPC285339
0.5926 Remote Similarity NPC71090
0.5833 Remote Similarity NPC194519
0.5833 Remote Similarity NPC137685
0.55 Remote Similarity NPC9370
0.55 Remote Similarity NPC287495
0.5439 Remote Similarity NPC469612
0.5439 Remote Similarity NPC469614
0.5323 Remote Similarity NPC601893
0.5312 Remote Similarity NPC5851
0.5312 Remote Similarity NPC481839
0.5231 Remote Similarity NPC86030
0.5077 Remote Similarity NPC147821
0.5077 Remote Similarity NPC319625
0.5077 Remote Similarity NPC183181
0.5077 Remote Similarity NPC41706

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC293701 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