Natural Product: NPC128293

Natural Product IDNPC128293
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Amorphigenin
IUPAC Name n.a.
Synonyms Amorphigenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465552
PubChem CID 92207
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001607] Rotenoids
          • [CHEMONTID:0003528] Rotenones

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 ZJMLELXRQUXRIU-HBGVWJBISA-N
Standard InCHI InChI=1S/C23H22O7/c1-11(9-24)16-7-14-15(29-16)5-4-12-22(25)21-13-6-18(26-2)19(27-3)8-17(13)28-10-20(21)30-23(12)14/h4-6,8,16,20-21,24H,1,7,9-10H2,2-3H3/t16-,20-,21+/m1/s1
SMILES OCC(=C)[C@@H]1Oc2c(C1)c1O[C@@H]3COc4c([C@@H]3C(=O)c1cc2)cc(c(c4)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   410.14 Volume:   404.022
?
Van der Waals volume.
Dense:   1.015 LogP:   2.931
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.906
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.111
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   27.0
TPSA:   83.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.776 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.031 Fsp3:   0.348
MCE-18:   93.032
?
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:   0.324 Fluc inhibitor:   0.776
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.237
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.17
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.081 Promiscuous compounds:   0.785

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.796 MDCK Permeability:   -4.643
Pgp-inhibitor:   0.312 Pgp-substrate:   0.023
PAMPA:   0.01
?
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%):   0.041 30% Bioavailability (F30%):   0.017
50% Bioavailability (F50%):   0.419

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.48 MRP1:   0.905
Plasma Protein Binding (PPB):   87.475% Volume Distribution (VD):   0.138
Fu: 13.161%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.513
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.561
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.036 CYP1A2-substrate:   0.022
CYP2C19-inhibitor:   0.221 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.153 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.564 CYP2D6-substrate:   0.596
CYP3A4-inhibitor:   0.455 CYP3A4-substrate:   0.988
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.669
HLM stability:   0.53
?
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):  8.615 Half-life (T1/2):  2.263

ADMET: Toxicity

hERG Blockers:  0.133 hERG Blockers (10um):  0.321
Human Hepatotoxicity (H-HT):  0.882 Drug-induced Liver Injury (DILI):  0.964
AMES Toxicity:  0.81 Rat Oral Acute Toxicity:  0.72
Maximum Recommended Daily Dose:  0.588 Skin Sensitization:  0.994
Carcinogencity:  0.579 Eye Corrosion:  0.001
Eye Irritation:  0.867 Respiratory Toxicity:  0.891
Drug-induced Neurotoxicity:  0.783 Ototoxicity:  0.805
Hematotoxicity:  0.793 Drug-induced Nephrotoxicity:  0.914
Genotoxicity:  0.924 RPMI-8226 Immunitoxicity:  0.388
A549 Cytotoxicity:  0.583 Hek293 Cytotoxicity:  0.711
BCF:   1.327
?
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:   3.756
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.837
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.066
?
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
NPO401 Berchemia discolor Species Rhamnaceae Eukaryota n.a. Tanzanian n.a. PMID[17125241]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18841906]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[28075580]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8326318]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8350086]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO401 Berchemia discolor Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO401 Berchemia discolor Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16886 Amorpha fruticosa 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
NPT672 Cell line TE-671 Homo sapiens ED50 < 0.01 ug ml-1 PMID[7903980]
NPT1091 Cell line RPMI-7951 Homo sapiens ED50 = 0.05 ug ml-1 PMID[16933872]
NPT168 Cell line P388 Mus musculus ED50 = 0.04 ug ml-1 DrugMatrix in vitro pharmacology data
NPT81 Cell line A549 Homo sapiens ED50 = 0.05 ug ml-1 DrugMatrix in vitro pharmacology data
NPT180 Cell line HCT-8 Homo sapiens ED50 = 0.03 ug ml-1 DrugMatrix in vitro pharmacology data
NPT91 Cell line KB Homo sapiens ED50 = 0.04 ug ml-1 DrugMatrix in vitro pharmacology data
NPT80 Cell line Raji Homo sapiens Activity = 80.0 % PMID[23327905]
NPT1034 Cell line Lu1 Homo sapiens ED50 = 4.8 ug ml-1 PMID[19916529]
NPT858 Cell line LNCaP Homo sapiens ED50 = 7.9 ug ml-1 PMID[15646539]
NPT83 Cell line MCF7 Homo sapiens ED50 > 20.0 ug ml-1 PMID[15646539]
NPT858 Cell line LNCaP Homo sapiens ED50 = 0.3 uM PMID[32459967]
NPT2 Others Unspecified n.a. Activity = 64.2 % PMID[24479418]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[19874044]
NPT2 Others Unspecified n.a. Activity = 31.7 % PMID[23628332]

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
- Mus musculus LD50 = 2.6 mg/kg ToxVal

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 NPC128293 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
0.8548 High Similarity NPC239374
0.8548 High Similarity NPC298093
0.8548 High Similarity NPC600423
0.7576 Intermediate Similarity NPC173292
0.6528 Remote Similarity NPC121333
0.6479 Remote Similarity NPC478962
0.6389 Remote Similarity NPC479307
0.6389 Remote Similarity NPC273959
0.6071 Remote Similarity NPC473883
0.5867 Remote Similarity NPC103307
0.5846 Remote Similarity NPC602167
0.5811 Remote Similarity NPC165549
0.5733 Remote Similarity NPC152477
0.5658 Remote Similarity NPC216795

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC128293 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
0.8548 High Similarity NPD5494 Approved

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