Natural Product: NPC474034

Natural Product IDNPC474034
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-3',4',7,8'-Tetrahydroxy-2',2'-Dimethyl-2,6'-Bichroman-4-One
IUPAC Name (2S)-7-hydroxy-2-(3,4,8-trihydroxy-2,2-dimethyl-3,4-dihydrochromen-6-yl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458815
PubChem CID 44589233
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans
            • [CHEMONTID:0003506] 3'-prenylated flavanones

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 CKBIVADBUPGTKI-DMKPSLHHSA-N
Standard InCHI InChI=1S/C20H20O7/c1-20(2)19(25)17(24)12-5-9(6-14(23)18(12)27-20)15-8-13(22)11-4-3-10(21)7-16(11)26-15/h3-7,15,17,19,21,23-25H,8H2,1-2H3/t15-,17?,19?/m0/s1
SMILES CC1(C(C(C2=C(O1)C(=CC(=C2)C3CC(=O)C4=C(O3)C=C(C=C4)O)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.12 Volume:   363.327
?
Van der Waals volume.
Dense:   1.024 LogP:   1.847
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.934
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.018
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   116.45
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.607 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.964 Fsp3:   0.35
MCE-18:   87.63
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.285 Fluc inhibitor:   0.4
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.55
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.304
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.174 Promiscuous compounds:   0.016

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.53 MDCK Permeability:   -4.797
Pgp-inhibitor:   0.039 Pgp-substrate:   0.212
PAMPA:   0.854
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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):   0.061
20% Bioavailability (F20%):   0.246 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.944
Plasma Protein Binding (PPB):   76.883% Volume Distribution (VD):   0.306
Fu: 26.545%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.326
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.913
BSEP inhibitor:   0.804

ADMET: Metabolism

CYP1A2-inhibitor:   0.014 CYP1A2-substrate:   0.507
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.915
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.457
CYP3A4-inhibitor:   0.576 CYP3A4-substrate:   0.045
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.91
HLM stability:   0.324
?
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):  6.873 Half-life (T1/2):  2.017

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.544
Human Hepatotoxicity (H-HT):  0.604 Drug-induced Liver Injury (DILI):  0.288
AMES Toxicity:  0.654 Rat Oral Acute Toxicity:  0.492
Maximum Recommended Daily Dose:  0.638 Skin Sensitization:  0.175
Carcinogencity:  0.599 Eye Corrosion:  0.001
Eye Irritation:  0.865 Respiratory Toxicity:  0.55
Drug-induced Neurotoxicity:  0.319 Ototoxicity:  0.638
Hematotoxicity:  0.131 Drug-induced Nephrotoxicity:  0.363
Genotoxicity:  0.833 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.248 Hek293 Cytotoxicity:  0.657
BCF:   0.756
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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:   3.423
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.207
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.303
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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
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8526 Erythrina abyssinica 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 > 60000.0 nM PMID[23079524]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC474034 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
0.7344 Intermediate Similarity NPC474033
0.5915 Remote Similarity NPC475790
0.5833 Remote Similarity NPC329225
0.5833 Remote Similarity NPC147686
0.5806 Remote Similarity NPC264083
0.5714 Remote Similarity NPC1612
0.5714 Remote Similarity NPC183959
0.5645 Remote Similarity NPC476480
0.5645 Remote Similarity NPC84585
0.5588 Remote Similarity NPC143896
0.5429 Remote Similarity NPC221432
0.5429 Remote Similarity NPC257097
0.5342 Remote Similarity NPC23728
0.5205 Remote Similarity NPC174953
0.5139 Remote Similarity NPC68104
0.5077 Remote Similarity NPC472460
0.5067 Remote Similarity NPC291508

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474034 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
0.5833 Remote Similarity NPD1549 Phase 2

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