Natural Product: NPC121333

Natural Product IDNPC121333
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dabinol
IUPAC Name n.a.
Synonyms 12A-Hydroxyamorphigenin; 12Abeta-Hydroxyamorphigenin; Dabinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465761
PubChem CID 44593485
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 MYQAATJJIDGOMQ-AYPBNUJASA-N
Standard InCHI InChI=1S/C23H22O8/c1-11(9-24)16-6-13-15(30-16)5-4-12-21(13)31-20-10-29-17-8-19(28-3)18(27-2)7-14(17)23(20,26)22(12)25/h4-5,7-8,16,20,24,26H,1,6,9-10H2,2-3H3/t16-,20-,23-/m1/s1
SMILES C=C(CO)[C@H]1Cc2c(ccc3c2O[C@@H]2COc4cc(c(cc4[C@@]2(C3=O)O)OC)OC)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   426.13 Volume:   412.812
?
Van der Waals volume.
Dense:   1.032 LogP:   1.787
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.148
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.159
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   27.0
TPSA:   103.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.714 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.179 Fsp3:   0.348
MCE-18:   99.677
?
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:   0.307 Fluc inhibitor:   0.256
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.341
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.194
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.101 Promiscuous compounds:   0.382

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.895 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.014 Pgp-substrate:   0.02
PAMPA:   0.278
?
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):   0.007
20% Bioavailability (F20%):   0.349 30% Bioavailability (F30%):   0.119
50% Bioavailability (F50%):   0.908

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.755
Plasma Protein Binding (PPB):   85.102% Volume Distribution (VD):   0.134
Fu: 16.878%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.838
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.071
BSEP inhibitor:   0.958

ADMET: Metabolism

CYP1A2-inhibitor:   0.014 CYP1A2-substrate:   0.205
CYP2C19-inhibitor:   0.021 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.035 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.112 CYP2D6-substrate:   0.948
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.575
HLM stability:   0.838
?
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):  10.042 Half-life (T1/2):  2.131

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.238
Human Hepatotoxicity (H-HT):  0.864 Drug-induced Liver Injury (DILI):  0.701
AMES Toxicity:  0.821 Rat Oral Acute Toxicity:  0.413
Maximum Recommended Daily Dose:  0.558 Skin Sensitization:  0.974
Carcinogencity:  0.705 Eye Corrosion:  0.001
Eye Irritation:  0.838 Respiratory Toxicity:  0.683
Drug-induced Neurotoxicity:  0.51 Ototoxicity:  0.771
Hematotoxicity:  0.541 Drug-induced Nephrotoxicity:  0.877
Genotoxicity:  0.65 RPMI-8226 Immunitoxicity:  0.201
A549 Cytotoxicity:  0.179 Hek293 Cytotoxicity:  0.469
BCF:   1.229
?
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:   3.652
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.474
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.862
?
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
NPT180 Cell line HCT-8 Homo sapiens ED50 < 0.001 ug ml-1 PMID[21723121]
NPT1091 Cell line RPMI-7951 Homo sapiens ED50 < 0.001 ug ml-1 PMID[21723121]
NPT91 Cell line KB Homo sapiens ED50 < 0.001 ug ml-1 DrugMatrix in vitro pharmacology data
NPT168 Cell line P388 Mus musculus ED50 < 0.001 ug ml-1 PMID[17512094]
NPT81 Cell line A549 Homo sapiens ED50 < 0.001 ug ml-1 PMID[17512094]
NPT672 Cell line TE-671 Homo sapiens ED50 < 0.001 ug ml-1 PMID[16378361]
NPT80 Cell line Raji Homo sapiens Activity = 80.0 % PMID[17497807]
NPT1034 Cell line Lu1 Homo sapiens ED50 = 3.1 ug ml-1 DrugMatrix in vivo data: Pathology
NPT858 Cell line LNCaP Homo sapiens ED50 = 5.4 ug ml-1 PMID[26988298]
NPT83 Cell line MCF7 Homo sapiens ED50 = 13.1 ug ml-1 PMID[26988298]
NPT1864 Cell line L5178Y Mus musculus IC50 = 200.0 nM PMID[28075580]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[9873492]
NPT2 Others Unspecified n.a. Activity = 89.7 % PMID[20536188]
NPT2 Others Unspecified n.a. Activity = 24.2 % PMID[7852999]

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 NPC121333 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
0.8889 High Similarity NPC152477
0.7612 Intermediate Similarity NPC242395
0.6528 Remote Similarity NPC128293
0.6364 Remote Similarity NPC607486
0.6184 Remote Similarity NPC156635
0.6164 Remote Similarity NPC609259
0.6133 Remote Similarity NPC8965
0.5921 Remote Similarity NPC74559
0.5775 Remote Similarity NPC234052
0.5714 Remote Similarity NPC611309
0.5479 Remote Similarity NPC603764
0.5467 Remote Similarity NPC239374
0.5467 Remote Similarity NPC298093
0.5467 Remote Similarity NPC600423
0.5278 Remote Similarity NPC605420
0.5195 Remote Similarity NPC150131
0.5122 Remote Similarity NPC67302
0.5122 Remote Similarity NPC123696
0.5068 Remote Similarity NPC105161

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC121333 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
0.5467 Remote 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