Natural Product: NPC241975

Natural Product IDNPC241975
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dihydroxy-6-(3-Methylbutanoyl)-8-(3-Methylbut-2-Enyl)-4-Pentylchromen-2-One
IUPAC Name 5,7-dihydroxy-6-(3-methylbutanoyl)-8-(3-methylbut-2-enyl)-4-pentylchromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689177
PubChem CID 51040689
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0002908] Hydroxycoumarins
          • [CHEMONTID:0002909] 7-hydroxycoumarins

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 XLQSXCISSFNQTD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H32O5/c1-6-7-8-9-16-13-19(26)29-24-17(11-10-14(2)3)22(27)21(23(28)20(16)24)18(25)12-15(4)5/h10,13,15,27-28H,6-9,11-12H2,1-5H3
SMILES CCCCCc1cc(=O)oc2c(CC=C(C)C)c(c(C(=O)CC(C)C)c(c12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.22 Volume:   432.043
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Van der Waals volume.
Dense:   0.926 LogP:   5.733
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.195
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.025
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   14.0
TPSA:   87.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.245 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.929 Fsp3:   0.5
MCE-18:   17.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.905 Fluc inhibitor:   0.068
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.948
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.551
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.175 Promiscuous compounds:   0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.756 MDCK Permeability:   -4.639
Pgp-inhibitor:   0.988 Pgp-substrate:   0.031
PAMPA:   0.011
?
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):   0.059
20% Bioavailability (F20%):   0.757 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.974
Plasma Protein Binding (PPB):   97.474% Volume Distribution (VD):   0.187
Fu: 2.951%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.962 BCRP inhibitor:   0.619
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.912 CYP2C9-substrate:   0.982
CYP2D6-inhibitor:   0.033 CYP2D6-substrate:   0.488
CYP3A4-inhibitor:   0.033 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  3.257 Half-life (T1/2):  0.866

ADMET: Toxicity

hERG Blockers:  0.181 hERG Blockers (10um):  0.608
Human Hepatotoxicity (H-HT):  0.546 Drug-induced Liver Injury (DILI):  0.364
AMES Toxicity:  0.159 Rat Oral Acute Toxicity:  0.585
Maximum Recommended Daily Dose:  0.499 Skin Sensitization:  0.851
Carcinogencity:  0.142 Eye Corrosion:  0.011
Eye Irritation:  0.782 Respiratory Toxicity:  0.946
Drug-induced Neurotoxicity:  0.133 Ototoxicity:  0.458
Hematotoxicity:  0.348 Drug-induced Nephrotoxicity:  0.699
Genotoxicity:  0.029 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.529 Hek293 Cytotoxicity:  0.453
BCF:   2.048
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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:   5.021
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.627
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.235
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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
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[21214226]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. stem n.a. PMID[21214226]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. Database[FooDB]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21645 Mammea americana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21645 Mammea americana Species Calophyllaceae 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
NPT396 Cell line T47D Homo sapiens IC50 = 3130.0 nM PMID[21214226]
NPT306 Cell line PC-3 Homo sapiens IC50 = 3360.0 nM PMID[21214226]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 4190.0 nM PMID[21214226]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 4120.0 nM PMID[21214226]

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 NPC241975 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
0.8667 High Similarity NPC199458
0.8254 Intermediate Similarity NPC470083
0.7576 Intermediate Similarity NPC19476
0.7273 Intermediate Similarity NPC96216
0.7077 Intermediate Similarity NPC138047
0.6667 Remote Similarity NPC219584
0.6618 Remote Similarity NPC183639
0.6377 Remote Similarity NPC294432
0.6027 Remote Similarity NPC1886
0.5915 Remote Similarity NPC474939
0.5789 Remote Similarity NPC184738
0.5775 Remote Similarity NPC131782
0.5775 Remote Similarity NPC474624
0.5455 Remote Similarity NPC288910
0.5405 Remote Similarity NPC196586
0.5263 Remote Similarity NPC36181
0.5062 Remote Similarity NPC118059

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC241975 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
NPD

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