Natural Product: NPC470402

Natural Product IDNPC470402
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Amyrisin B
IUPAC Name 5,7-dihydroxy-2-[4-(2-hydroxy-3-methylbut-3-enoxy)phenyl]-6-methoxychromen-4-one
Synonyms Amyrisin B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2023532
PubChem CID 57381727
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-O-methylated flavonoids

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 RSFSMBFMVJOURC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O7/c1-11(2)16(24)10-27-13-6-4-12(5-7-13)17-8-14(22)19-18(28-17)9-15(23)21(26-3)20(19)25/h4-9,16,23-25H,1,10H2,2-3H3
SMILES COc1c(O)cc2c(c1O)c(=O)cc(o2)c1ccc(cc1)OCC(C(=C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   384.12 Volume:   383.906
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Van der Waals volume.
Dense:   1.001 LogP:   3.117
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.743
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.874
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   109.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.56 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.178 Fsp3:   0.19
MCE-18:   40.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.575 Fluc inhibitor:   0.596
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.972
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.529
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.057 Promiscuous compounds:   0.357

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.074 MDCK Permeability:   -4.736
Pgp-inhibitor:   0.034 Pgp-substrate:   0.275
PAMPA:   0.276
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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):   0.054
20% Bioavailability (F20%):   0.269 30% Bioavailability (F30%):   0.755
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.026 MRP1:   0.742
Plasma Protein Binding (PPB):   97.545% Volume Distribution (VD):   -0.262
Fu: 1.997%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.929
BSEP inhibitor:   0.361

ADMET: Metabolism

CYP1A2-inhibitor:   0.282 CYP1A2-substrate:   0.475
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.829 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.047
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.773
?
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):  5.815 Half-life (T1/2):  1.159

ADMET: Toxicity

hERG Blockers:  0.129 hERG Blockers (10um):  0.507
Human Hepatotoxicity (H-HT):  0.422 Drug-induced Liver Injury (DILI):  0.725
AMES Toxicity:  0.549 Rat Oral Acute Toxicity:  0.289
Maximum Recommended Daily Dose:  0.739 Skin Sensitization:  0.215
Carcinogencity:  0.721 Eye Corrosion:  0.006
Eye Irritation:  0.943 Respiratory Toxicity:  0.73
Drug-induced Neurotoxicity:  0.104 Ototoxicity:  0.513
Hematotoxicity:  0.155 Drug-induced Nephrotoxicity:  0.094
Genotoxicity:  0.867 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.259 Hek293 Cytotoxicity:  0.572
BCF:   1.337
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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:   3.967
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.242
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.732
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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
NPO1170 Amyris madrensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[22260294]
NPO1170 Amyris madrensis Species Rutaceae 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
NPT306 Cell line PC-3 Homo sapiens IC50 = 17500.0 nM PMID[17889536]
NPT90 Cell line DU-145 Homo sapiens IC50 = 17500.0 nM PMID[25008455]

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 NPC470402 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
0.7719 Intermediate Similarity NPC156222
0.6885 Remote Similarity NPC256283
0.6866 Remote Similarity NPC213622
0.6774 Remote Similarity NPC255350
0.6667 Remote Similarity NPC293183
0.6557 Remote Similarity NPC241498
0.6452 Remote Similarity NPC100887
0.6032 Remote Similarity NPC284552
0.6 Remote Similarity NPC83508
0.5781 Remote Similarity NPC44079
0.5692 Remote Similarity NPC184136
0.5692 Remote Similarity NPC231772
0.5692 Remote Similarity NPC145379
0.5538 Remote Similarity NPC203891
0.5303 Remote Similarity NPC274327
0.5303 Remote Similarity NPC29353
0.5224 Remote Similarity NPC57030
0.5217 Remote Similarity NPC160951
0.5217 Remote Similarity NPC52005
0.5185 Remote Similarity NPC475942
0.5147 Remote Similarity NPC603662
0.5075 Remote Similarity NPC600177
0.5072 Remote Similarity NPC115798
0.5072 Remote Similarity NPC69394

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470402 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
0.6774 Remote Similarity NPD2801 Pre-clinical

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