Natural Product: NPC258671

Natural Product IDNPC258671
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cimicifugic Acid F
IUPAC Name (2R,3S)-2-hydroxy-3-[(E)-3-(3-hydroxy-4-methoxyphenyl)prop-2-enoyl]oxy-2-[(4-hydroxyphenyl)methyl]butanedioic acid
Synonyms Cimicifugic Acid F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1097936
PubChem CID 6450179
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 WBGMKAAMRFEBHK-PZTMCFHLSA-N
Standard InCHI InChI=1S/C21H20O10/c1-30-16-8-4-12(10-15(16)23)5-9-17(24)31-18(19(25)26)21(29,20(27)28)11-13-2-6-14(22)7-3-13/h2-10,18,22-23,29H,11H2,1H3,(H,25,26)(H,27,28)/b9-5+/t18-,21-/m1/s1
SMILES COc1ccc(cc1O)/C=C/C(=O)O[C@@H]([C@@](C(=O)O)(Cc1ccc(cc1)O)O)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.11 Volume:   416.197
?
Van der Waals volume.
Dense:   1.038 LogP:   1.632
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.81
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.647
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   16.0
TPSA:   170.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.286 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.441 Fsp3:   0.19
MCE-18:   36.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.484 Fluc inhibitor:   0.996
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.542
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.418 Promiscuous compounds:   0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.234 MDCK Permeability:   -5.169
Pgp-inhibitor:   0.0 Pgp-substrate:   0.032
PAMPA:   0.99
?
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):   0.019
20% Bioavailability (F20%):   0.351 30% Bioavailability (F30%):   0.881
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.485
Plasma Protein Binding (PPB):   78.616% Volume Distribution (VD):   -0.55
Fu: 18.449%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.719

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.015
CYP2C9-inhibitor:   0.977 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.274
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.981
HLM stability:   0.014
?
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):  2.785 Half-life (T1/2):  2.429

ADMET: Toxicity

hERG Blockers:  0.022 hERG Blockers (10um):  0.028
Human Hepatotoxicity (H-HT):  0.725 Drug-induced Liver Injury (DILI):  0.584
AMES Toxicity:  0.273 Rat Oral Acute Toxicity:  0.16
Maximum Recommended Daily Dose:  0.402 Skin Sensitization:  0.983
Carcinogencity:  0.169 Eye Corrosion:  0.016
Eye Irritation:  0.934 Respiratory Toxicity:  0.258
Drug-induced Neurotoxicity:  0.19 Ototoxicity:  0.662
Hematotoxicity:  0.15 Drug-induced Nephrotoxicity:  0.876
Genotoxicity:  0.937 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.016 Hek293 Cytotoxicity:  0.07
BCF:   0.522
?
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:   3.338
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.439
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.948
?
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
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[20121210]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[20192237]
NPO32999 cimicifuga heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[20192237]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[28558206]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[32031796]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15890 Cimicifuga foetida Species Ranunculaceae 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
NPT2 Others Unspecified n.a. IC50 = 92000.0 nM PMID[20192237]

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 NPC258671 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
0.871 High Similarity NPC221383
0.8125 Intermediate Similarity NPC95498
0.8125 Intermediate Similarity NPC304956
0.7903 Intermediate Similarity NPC279676
0.7833 Intermediate Similarity NPC108553
0.7344 Intermediate Similarity NPC156709
0.7206 Intermediate Similarity NPC143892
0.7206 Intermediate Similarity NPC299090
0.7206 Intermediate Similarity NPC246566
0.7101 Intermediate Similarity NPC283081
0.7031 Intermediate Similarity NPC179505
0.6818 Remote Similarity NPC67349
0.6338 Remote Similarity NPC53884
0.619 Remote Similarity NPC223335
0.619 Remote Similarity NPC40920
0.5588 Remote Similarity NPC198388
0.5568 Remote Similarity NPC44507
0.5556 Remote Similarity NPC289690
0.5294 Remote Similarity NPC18074
0.5294 Remote Similarity NPC5419
0.5294 Remote Similarity NPC25581
0.5294 Remote Similarity NPC61
0.5143 Remote Similarity NPC229264

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC258671 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