Natural Product: NPC5419

Natural Product IDNPC5419
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E/Z)-Rosmarinic Acid
IUPAC Name (2R)-3-(3,4-dihydroxyphenyl)-2-[3-(3,4-dihydroxyphenyl)prop-2-enoyloxy]propanoic acid
Synonyms Rosmarinic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2111558
PubChem CID 65035
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric acids and derivatives

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 DOUMFZQKYFQNTF-MRXNPFEDSA-N
Standard InCHI InChI=1S/C18H16O8/c19-12-4-1-10(7-14(12)21)3-6-17(23)26-16(18(24)25)9-11-2-5-13(20)15(22)8-11/h1-8,16,19-22H,9H2,(H,24,25)/t16-/m1/s1
SMILES O=C(O[C@@H](C(=O)O)Cc1ccc(c(c1)O)O)C=Cc1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   349.365
?
Van der Waals volume.
Dense:   1.031 LogP:   1.985
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.952
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.781
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   144.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.298 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.903 Fsp3:   0.111
MCE-18:   30.0
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.9 Fluc inhibitor:   0.97
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.302
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.659 Promiscuous compounds:   0.48

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.455 MDCK Permeability:   -4.968
Pgp-inhibitor:   0.0 Pgp-substrate:   0.006
PAMPA:   0.965
?
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%):   0.685 30% Bioavailability (F30%):   0.695
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.185
Plasma Protein Binding (PPB):   77.947% Volume Distribution (VD):   -0.348
Fu: 12.684%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.0
BSEP inhibitor:   0.008

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.947
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.954
HLM stability:   0.058
?
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):  16.588 Half-life (T1/2):  1.931

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.264
Human Hepatotoxicity (H-HT):  0.613 Drug-induced Liver Injury (DILI):  0.918
AMES Toxicity:  0.55 Rat Oral Acute Toxicity:  0.402
Maximum Recommended Daily Dose:  0.909 Skin Sensitization:  1.0
Carcinogencity:  0.052 Eye Corrosion:  0.017
Eye Irritation:  0.952 Respiratory Toxicity:  0.303
Drug-induced Neurotoxicity:  0.072 Ototoxicity:  0.877
Hematotoxicity:  0.029 Drug-induced Nephrotoxicity:  0.604
Genotoxicity:  0.993 RPMI-8226 Immunitoxicity:  0.009
A549 Cytotoxicity:  0.705 Hek293 Cytotoxicity:  0.084
BCF:   0.907
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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:   3.732
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.785
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.495
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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
NPO1504 Alicyclobacillus cycloheptanicus Species Alicyclobacillaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO10482 Clitocybe nebularis Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1504 Alicyclobacillus cycloheptanicus Species Alicyclobacillaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO10482 Clitocybe nebularis Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6795 Achillea sibirica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9057 Pitavia punctata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26694 Melilotus indicus Species Fabaceae 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
NPT32 Organism Mus musculus Mus musculus IC50 = 600.0 nM PMID[21388814]





 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 NPC5419 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 NPC18074
1.0 High Similarity NPC25581
1.0 High Similarity NPC61
0.88 High Similarity NPC198388
0.7857 Intermediate Similarity NPC289690
0.7586 Intermediate Similarity NPC38473
0.75 Intermediate Similarity NPC217052
0.75 Intermediate Similarity NPC329344
0.75 Intermediate Similarity NPC237506
0.75 Intermediate Similarity NPC32626
0.7258 Intermediate Similarity NPC160378
0.7018 Intermediate Similarity NPC179505
0.6792 Remote Similarity NPC132921
0.6667 Remote Similarity NPC251407
0.6667 Remote Similarity NPC168653
0.65 Remote Similarity NPC279676
0.623 Remote Similarity NPC156709
0.623 Remote Similarity NPC67349
0.6 Remote Similarity NPC221383
0.5857 Remote Similarity NPC41494
0.5857 Remote Similarity NPC186100
0.5857 Remote Similarity NPC189197
0.5821 Remote Similarity NPC283081
0.5775 Remote Similarity NPC272750
0.5763 Remote Similarity NPC228940
0.5741 Remote Similarity NPC147654
0.5672 Remote Similarity NPC143892
0.5672 Remote Similarity NPC299090
0.5672 Remote Similarity NPC246566
0.5616 Remote Similarity NPC300329
0.5574 Remote Similarity NPC108553
0.5517 Remote Similarity NPC488563
0.551 Remote Similarity NPC226250
0.5345 Remote Similarity NPC168799
0.5294 Remote Similarity NPC258671
0.527 Remote Similarity NPC301089
0.5254 Remote Similarity NPC470849
0.5205 Remote Similarity NPC221091
0.5205 Remote Similarity NPC259576
0.5192 Remote Similarity NPC95381
0.5161 Remote Similarity NPC475695
0.5135 Remote Similarity NPC144557
0.5132 Remote Similarity NPC87517
0.5132 Remote Similarity NPC216403
0.5082 Remote Similarity NPC155209
0.5079 Remote Similarity NPC13818
0.5079 Remote Similarity NPC219428
0.5077 Remote Similarity NPC6913

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC5419 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