Natural Product: NPC138047

Natural Product IDNPC138047
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Mammea B/Ab
IUPAC Name 5,7-dihydroxy-6-[(2R)-2-methylbutanoyl]-8-(3-methylbut-2-enyl)-4-propylchromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689182
PubChem CID 53326644
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 PQMOXTJVIYEOQL-CYBMUJFWSA-N
Standard InCHI InChI=1S/C22H28O5/c1-6-8-14-11-16(23)27-22-15(10-9-12(3)4)20(25)18(21(26)17(14)22)19(24)13(5)7-2/h9,11,13,25-26H,6-8,10H2,1-5H3/t13-/m1/s1
SMILES CCCc1cc(=O)oc2c1c(O)c(C(=O)[C@@H](CC)C)c(c2CC=C(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.19 Volume:   397.451
?
Van der Waals volume.
Dense:   0.936 LogP:   4.473
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.597
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.688
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 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:   0.41 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.426 Fsp3:   0.455
MCE-18:   34.0
?
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:   0.691 Fluc inhibitor:   0.032
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.93
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.517
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.209

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.802 MDCK Permeability:   -4.658
Pgp-inhibitor:   0.97 Pgp-substrate:   0.416
PAMPA:   0.036
?
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):   0.003
20% Bioavailability (F20%):   0.317 30% Bioavailability (F30%):   0.799
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.055 MRP1:   0.995
Plasma Protein Binding (PPB):   97.525% Volume Distribution (VD):   0.041
Fu: 2.468%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.931
OATP1B3 inhibitor:   0.74 BCRP inhibitor:   0.702
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.026 CYP2C9-substrate:   0.448
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.011
CYP3A4-inhibitor:   0.573 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.007 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):  3.114 Half-life (T1/2):  1.048

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.409
Human Hepatotoxicity (H-HT):  0.534 Drug-induced Liver Injury (DILI):  0.663
AMES Toxicity:  0.352 Rat Oral Acute Toxicity:  0.6
Maximum Recommended Daily Dose:  0.818 Skin Sensitization:  0.951
Carcinogencity:  0.203 Eye Corrosion:  0.009
Eye Irritation:  0.742 Respiratory Toxicity:  0.96
Drug-induced Neurotoxicity:  0.282 Ototoxicity:  0.414
Hematotoxicity:  0.365 Drug-induced Nephrotoxicity:  0.69
Genotoxicity:  0.767 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.442 Hek293 Cytotoxicity:  0.599
BCF:   1.833
?
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:   4.754
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.477
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.957
?
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 Activity = 1.0 uM PMID[23398362]
NPT396 Cell line T47D Homo sapiens IC50 = 5520.0 nM PMID[24460410]
NPT306 Cell line PC-3 Homo sapiens IC50 = 10500.0 nM PMID[19105653]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 9960.0 nM PMID[21214226]
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 8210.0 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 NPC138047 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
0.8644 High Similarity NPC470083
0.8136 Intermediate Similarity NPC199458
0.7581 Intermediate Similarity NPC196586
0.7419 Intermediate Similarity NPC474939
0.7258 Intermediate Similarity NPC131782
0.7258 Intermediate Similarity NPC474624
0.7077 Intermediate Similarity NPC241975
0.6418 Remote Similarity NPC219584
0.6364 Remote Similarity NPC183639
0.6324 Remote Similarity NPC470296
0.6324 Remote Similarity NPC196459
0.6029 Remote Similarity NPC96216
0.5882 Remote Similarity NPC294432
0.5634 Remote Similarity NPC19476
0.5352 Remote Similarity NPC470909
0.527 Remote Similarity NPC470555
0.5135 Remote Similarity NPC1886
0.5132 Remote Similarity NPC184738
0.5067 Remote Similarity NPC133060
0.5067 Remote Similarity NPC470556

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC138047 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