Natural Product: NPC155564

Natural Product IDNPC155564
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Geranin A
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL447152
PubChem CID 44566352
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 LQRHGTVFFPMWCG-TXZJYACMSA-N
Standard InCHI InChI=1S/C30H24O10/c31-15-5-1-13(2-6-15)27-21(36)11-18-19(34)12-23-25(28(18)38-27)26-24-20(35)9-17(33)10-22(24)39-30(40-23,29(26)37)14-3-7-16(32)8-4-14/h1-10,12,21,26-27,29,31-37H,11H2/t21-,26+,27+,29+,30-/m0/s1
SMILES c1cc(ccc1[C@@H]1[C@H](Cc2c(cc3c([C@H]4c5c(cc(cc5O[C@](c5ccc(cc5)O)([C@@H]4O)O3)O)O)c2O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   544.14 Volume:   523.806
?
Van der Waals volume.
Dense:   1.039 LogP:   2.411
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.597
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.181
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   37.0
TPSA:   169.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   7.0 Rings:   7.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.199 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.178 Fsp3:   0.2
MCE-18:   136.667
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.777 Fluc inhibitor:   0.111
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.683
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.777
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.489 Promiscuous compounds:   0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.94 MDCK Permeability:   -4.945
Pgp-inhibitor:   0.001 Pgp-substrate:   0.98
PAMPA:   0.031
?
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%):   0.138 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.928
Plasma Protein Binding (PPB):   93.786% Volume Distribution (VD):   0.504
Fu: 8.608%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.711
OATP1B3 inhibitor:   0.873 BCRP inhibitor:   0.258
BSEP inhibitor:   0.871

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.212
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.054 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.103 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.674
HLM stability:   0.0
?
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):  5.603 Half-life (T1/2):  3.131

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.542
Human Hepatotoxicity (H-HT):  0.961 Drug-induced Liver Injury (DILI):  0.708
AMES Toxicity:  0.46 Rat Oral Acute Toxicity:  0.78
Maximum Recommended Daily Dose:  0.919 Skin Sensitization:  0.997
Carcinogencity:  0.079 Eye Corrosion:  0.0
Eye Irritation:  0.741 Respiratory Toxicity:  0.943
Drug-induced Neurotoxicity:  0.617 Ototoxicity:  0.826
Hematotoxicity:  0.023 Drug-induced Nephrotoxicity:  0.801
Genotoxicity:  0.958 RPMI-8226 Immunitoxicity:  0.35
A549 Cytotoxicity:  0.993 Hek293 Cytotoxicity:  0.992
BCF:   1.288
?
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:   3.915
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.91
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.452
?
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
NPO6918 Geranium niveum Species Geraniaceae Eukaryota n.a. n.a. n.a. PMID[10346950]
NPO6918 Geranium niveum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6918 Geranium niveum Species Geraniaceae 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
NPT992 Organism Entamoeba histolytica Entamoeba histolytica IC50 = 184.7 ug.mL-1 PMID[23644188]
NPT2645 Organism Giardia intestinalis Giardia intestinalis IC50 = 2.4 ug.mL-1 PMID[20558071]

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 NPC155564 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
0.9062 High Similarity NPC46283
0.9062 High Similarity NPC469944
0.9062 High Similarity NPC134911
0.8676 High Similarity NPC471404
0.8333 Intermediate Similarity NPC272552
0.8333 Intermediate Similarity NPC226108
0.8333 Intermediate Similarity NPC322899
0.7857 Intermediate Similarity NPC478616
0.7857 Intermediate Similarity NPC478339
0.7826 Intermediate Similarity NPC44192
0.7143 Intermediate Similarity NPC78074
0.7051 Intermediate Similarity NPC478337
0.7051 Intermediate Similarity NPC478338
0.6974 Remote Similarity NPC147743
0.6974 Remote Similarity NPC4809
0.6974 Remote Similarity NPC73517
0.6627 Remote Similarity NPC478617
0.6582 Remote Similarity NPC86630
0.65 Remote Similarity NPC478340
0.6386 Remote Similarity NPC159526
0.619 Remote Similarity NPC484331
0.6098 Remote Similarity NPC106601
0.6098 Remote Similarity NPC151474
0.6024 Remote Similarity NPC212614
0.6024 Remote Similarity NPC205613
0.5862 Remote Similarity NPC484330
0.5833 Remote Similarity NPC277331
0.5833 Remote Similarity NPC100482
0.5823 Remote Similarity NPC306267
0.5789 Remote Similarity NPC211561
0.5747 Remote Similarity NPC12326
0.5714 Remote Similarity NPC207179
0.5714 Remote Similarity NPC167571
0.5714 Remote Similarity NPC278552
0.5618 Remote Similarity NPC185231
0.5616 Remote Similarity NPC58190
0.5616 Remote Similarity NPC108811
0.5616 Remote Similarity NPC170103
0.5616 Remote Similarity NPC236202
0.5616 Remote Similarity NPC262911
0.5616 Remote Similarity NPC202742
0.5616 Remote Similarity NPC601999
0.5541 Remote Similarity NPC246202
0.5541 Remote Similarity NPC224161
0.5541 Remote Similarity NPC46335
0.5541 Remote Similarity NPC279406
0.5541 Remote Similarity NPC486519
0.55 Remote Similarity NPC20050
0.5316 Remote Similarity NPC186228
0.5256 Remote Similarity NPC70409
0.5256 Remote Similarity NPC204770
0.5256 Remote Similarity NPC600551
0.5256 Remote Similarity NPC601980
0.5256 Remote Similarity NPC602065
0.5256 Remote Similarity NPC611024
0.519 Remote Similarity NPC226809
0.519 Remote Similarity NPC601997
0.519 Remote Similarity NPC609211
0.519 Remote Similarity NPC610665
0.5135 Remote Similarity NPC96576
0.5132 Remote Similarity NPC294558
0.5132 Remote Similarity NPC18185
0.5132 Remote Similarity NPC263940
0.5062 Remote Similarity NPC278548

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC155564 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