Natural Product: NPC474288

Natural Product IDNPC474288
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rhinacanthin F
IUPAC Name dimethyl 2-(1,3-benzodioxol-5-ylmethyl)-3-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]butanedioate
Synonyms Rhinacanthin F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464737
PubChem CID 10411189
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 KTVCMDZMYIVGEN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H24O9/c1-26-19-9-14(10-20-21(19)32-12-31-20)7-16(23(25)28-3)15(22(24)27-2)6-13-4-5-17-18(8-13)30-11-29-17/h4-5,8-10,15-16H,6-7,11-12H2,1-3H3
SMILES COC1=CC(=CC2=C1OCO2)CC(C(CC3=CC4=C(C=C3)OCO4)C(=O)OC)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   444.14 Volume:   430.159
?
Van der Waals volume.
Dense:   1.033 LogP:   2.767
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.918
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.256
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   22.0
TPSA:   98.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.569 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.38 Fsp3:   0.391
MCE-18:   71.875
?
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:   0.043 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.516
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.188 Promiscuous compounds:   0.014

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.046 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.959 Pgp-substrate:   0.003
PAMPA:   0.025
?
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):   0.001
20% Bioavailability (F20%):   0.27 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.843

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.684 MRP1:   0.905
Plasma Protein Binding (PPB):   98.215% Volume Distribution (VD):   -0.416
Fu: 1.733%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.023
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.869 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.985 CYP2C19-substrate:   0.986
CYP2C9-inhibitor:   0.794 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.958 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.997 CYP2C8-inhibitor:   0.017
HLM stability:   0.919
?
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):  4.221 Half-life (T1/2):  0.529

ADMET: Toxicity

hERG Blockers:  0.453 hERG Blockers (10um):  0.674
Human Hepatotoxicity (H-HT):  0.726 Drug-induced Liver Injury (DILI):  0.397
AMES Toxicity:  0.293 Rat Oral Acute Toxicity:  0.538
Maximum Recommended Daily Dose:  0.889 Skin Sensitization:  0.081
Carcinogencity:  0.474 Eye Corrosion:  0.0
Eye Irritation:  0.01 Respiratory Toxicity:  0.647
Drug-induced Neurotoxicity:  0.676 Ototoxicity:  0.714
Hematotoxicity:  0.205 Drug-induced Nephrotoxicity:  0.429
Genotoxicity:  0.68 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.136 Hek293 Cytotoxicity:  0.522
BCF:   1.647
?
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:   4.169
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.121
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.191
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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
NPO3049 Rhinacanthus nasutus Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8463799]
NPO3049 Rhinacanthus nasutus Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8792629]
NPO3049 Rhinacanthus nasutus Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[9214738]
NPO3049 Rhinacanthus nasutus Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3049 Rhinacanthus nasutus Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3049 Rhinacanthus nasutus Species Acanthaceae 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
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 4.4 ug.mL-1 PMID[23558238]
NPT616 Cell line MDCK Canis lupus familiaris IC50 = 17.0 ug.mL-1 PMID[18715034]
NPT2 Others Unspecified n.a. Ratio IC50/EC50 = 6.8 n.a. PMID[25988621]
NPT2 Others Unspecified n.a. Ratio IC50/EC50 > 18.0 n.a. PMID[26358281]
NPT742 Organism Influenza A virus Influenza A virus EC50 = 3.1 ug.mL-1 PMID[18715034]
NPT742 Organism Influenza A virus Influenza A virus EC50 < 0.94 ug.mL-1 PMID[22360639]

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 NPC474288 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
0.7451 Intermediate Similarity NPC191158
0.7451 Intermediate Similarity NPC177644
0.6923 Remote Similarity NPC176586
0.6923 Remote Similarity NPC210354
0.6471 Remote Similarity NPC143895
0.64 Remote Similarity NPC192255
0.6327 Remote Similarity NPC196937
0.6275 Remote Similarity NPC92693
0.6226 Remote Similarity NPC205915
0.6154 Remote Similarity NPC40237
0.614 Remote Similarity NPC474158
0.6078 Remote Similarity NPC110958
0.6078 Remote Similarity NPC19890
0.6 Remote Similarity NPC11453
0.5957 Remote Similarity NPC344161
0.5778 Remote Similarity NPC80241
0.5778 Remote Similarity NPC301641
0.5778 Remote Similarity NPC485483
0.5763 Remote Similarity NPC145569
0.5738 Remote Similarity NPC216223
0.5625 Remote Similarity NPC150534
0.5614 Remote Similarity NPC185908
0.5614 Remote Similarity NPC482891
0.56 Remote Similarity NPC476748
0.5574 Remote Similarity NPC282291
0.5574 Remote Similarity NPC166137
0.551 Remote Similarity NPC600801
0.5424 Remote Similarity NPC293757
0.5424 Remote Similarity NPC668
0.5417 Remote Similarity NPC40352
0.5417 Remote Similarity NPC213711
0.541 Remote Similarity NPC56184
0.537 Remote Similarity NPC211386
0.5273 Remote Similarity NPC158737
0.5273 Remote Similarity NPC274356
0.5273 Remote Similarity NPC101748
0.5254 Remote Similarity NPC3982
0.5208 Remote Similarity NPC604144
0.5106 Remote Similarity NPC119949

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474288 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