Natural Product: NPC134911

Natural Product IDNPC134911
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Geranin B
IUPAC Name n.a.
Synonyms Geranin B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL499587
PubChem CID 44566353
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 GVKLXAPXNKDQGB-TXZJYACMSA-N
Standard InCHI InChI=1S/C30H24O11/c31-14-4-1-12(2-5-14)27-21(37)10-16-18(34)11-23-25(28(16)39-27)26-24-20(36)8-15(32)9-22(24)40-30(41-23,29(26)38)13-3-6-17(33)19(35)7-13/h1-9,11,21,26-27,29,31-38H,10H2/t21-,26+,27+,29+,30-/m0/s1
SMILES c1cc(ccc1[C@@H]1[C@H](Cc2c(cc3c([C@H]4c5c(cc(cc5O[C@](c5ccc(c(c5)O)O)([C@@H]4O)O3)O)O)c2O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   560.13 Volume:   532.596
?
Van der Waals volume.
Dense:   1.052 LogP:   2.108
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.16
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.371
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   37.0
TPSA:   189.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   8.0 Rings:   7.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.168 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.269 Fsp3:   0.2
MCE-18:   140.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.77 Fluc inhibitor:   0.059
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.727
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.743
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.495 Promiscuous compounds:   0.11

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -7.081 MDCK Permeability:   -4.928
Pgp-inhibitor:   0.0 Pgp-substrate:   0.722
PAMPA:   0.053
?
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%):   0.802 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.948
Plasma Protein Binding (PPB):   92.757% Volume Distribution (VD):   0.435
Fu: 9.771%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.935
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.079
BSEP inhibitor:   0.483

ADMET: Metabolism

CYP1A2-inhibitor:   0.663 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.431 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.057 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.957
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):  7.228 Half-life (T1/2):  3.605

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.606
Human Hepatotoxicity (H-HT):  0.959 Drug-induced Liver Injury (DILI):  0.85
AMES Toxicity:  0.536 Rat Oral Acute Toxicity:  0.81
Maximum Recommended Daily Dose:  0.923 Skin Sensitization:  1.0
Carcinogencity:  0.053 Eye Corrosion:  0.0
Eye Irritation:  0.698 Respiratory Toxicity:  0.952
Drug-induced Neurotoxicity:  0.195 Ototoxicity:  0.943
Hematotoxicity:  0.021 Drug-induced Nephrotoxicity:  0.697
Genotoxicity:  0.963 RPMI-8226 Immunitoxicity:  0.243
A549 Cytotoxicity:  0.999 Hek293 Cytotoxicity:  0.975
BCF:   1.349
?
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:   3.916
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.11
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.534
?
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]
NPO5183 Feretia apodanthera Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[23268742]
NPO16874 Campsiandra guayanensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23268742]
NPO5183 Feretia apodanthera Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8954 Torilis scabra Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO6918 Geranium niveum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO16874 Campsiandra guayanensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6918 Geranium niveum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5183 Feretia apodanthera Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO130 Galeopsis bifida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8954 Torilis scabra Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8136 Pterospermum heyneanum Species Malvaceae 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
NPT301 Individual protein Vascular endothelial growth factor receptor 1 Homo sapiens IC50 = 65000.0 nM PMID[23268742]
NPT4535 Individual protein Vascular endothelial growth factor A Homo sapiens Kd = 48.0 nM PMID[23268742]
NPT4536 Individual protein Placenta growth factor Homo sapiens Kd = 23.0 nM PMID[23268742]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 > 70000.0 nM PMID[23268742]
NPT15 Cell line Jurkat Homo sapiens IC50 > 70000.0 nM PMID[23268742]
NPT992 Organism Entamoeba histolytica Entamoeba histolytica IC50 = 13.6 ug.mL-1 DOI[10.1007/s00044-011-9767-1]
NPT2645 Organism Giardia intestinalis Giardia intestinalis IC50 = 6.0 ug.mL-1 PMID[10346950]

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 NPC134911 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
0.9265 High Similarity NPC471404
0.9231 High Similarity NPC272552
0.9231 High Similarity NPC226108
0.9231 High Similarity NPC322899
0.9091 High Similarity NPC46283
0.9091 High Similarity NPC469944
0.9062 High Similarity NPC155564
0.8696 High Similarity NPC478616
0.8696 High Similarity NPC478339
0.8406 Intermediate Similarity NPC44192
0.7895 Intermediate Similarity NPC78074
0.7792 Intermediate Similarity NPC478337
0.7792 Intermediate Similarity NPC478338
0.7733 Intermediate Similarity NPC147743
0.7733 Intermediate Similarity NPC4809
0.7733 Intermediate Similarity NPC73517
0.7317 Intermediate Similarity NPC478617
0.7308 Intermediate Similarity NPC86630
0.7215 Intermediate Similarity NPC478340
0.7073 Intermediate Similarity NPC159526
0.6867 Remote Similarity NPC484331
0.679 Remote Similarity NPC106601
0.679 Remote Similarity NPC151474
0.6707 Remote Similarity NPC212614
0.6707 Remote Similarity NPC205613
0.6395 Remote Similarity NPC12326
0.6322 Remote Similarity NPC484330
0.6125 Remote Similarity NPC306267
0.6067 Remote Similarity NPC185231
0.6 Remote Similarity NPC20050
0.5946 Remote Similarity NPC58190
0.5946 Remote Similarity NPC108811
0.5946 Remote Similarity NPC170103
0.5946 Remote Similarity NPC236202
0.5946 Remote Similarity NPC262911
0.5946 Remote Similarity NPC202742
0.5867 Remote Similarity NPC246202
0.5867 Remote Similarity NPC224161
0.5867 Remote Similarity NPC46335
0.5867 Remote Similarity NPC279406
0.5867 Remote Similarity NPC486519
0.5733 Remote Similarity NPC277331
0.5733 Remote Similarity NPC100482
0.557 Remote Similarity NPC70409
0.557 Remote Similarity NPC204770
0.557 Remote Similarity NPC600551
0.557 Remote Similarity NPC601980
0.557 Remote Similarity NPC602065
0.557 Remote Similarity NPC611024
0.55 Remote Similarity NPC226809
0.55 Remote Similarity NPC211561
0.5455 Remote Similarity NPC294558
0.5455 Remote Similarity NPC18185
0.5455 Remote Similarity NPC263940
0.5373 Remote Similarity NPC207179
0.5373 Remote Similarity NPC167571
0.5373 Remote Similarity NPC278552
0.5366 Remote Similarity NPC278548
0.5325 Remote Similarity NPC601999
0.5316 Remote Similarity NPC313116
0.5316 Remote Similarity NPC603340
0.5256 Remote Similarity NPC20757
0.5256 Remote Similarity NPC227516
0.5217 Remote Similarity NPC261619
0.5217 Remote Similarity NPC61477
0.5217 Remote Similarity NPC78770
0.5217 Remote Similarity NPC219876
0.5217 Remote Similarity NPC126029
0.5217 Remote Similarity NPC15658
0.5181 Remote Similarity NPC302549
0.5122 Remote Similarity NPC601997
0.5122 Remote Similarity NPC609211
0.5122 Remote Similarity NPC610665
0.5116 Remote Similarity NPC135021
0.5065 Remote Similarity NPC96576
0.506 Remote Similarity NPC186228
0.506 Remote Similarity NPC600630
0.506 Remote Similarity NPC607896
0.506 Remote Similarity NPC611369

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC134911 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
0.5217 Remote Similarity NPD1612 Clinical (unspecified phase)
0.5217 Remote Similarity NPD1613 Phase 4

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