Natural Product: NPC474624

Natural Product IDNPC474624
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Mammea B/Bb
IUPAC Name 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-enyl)-4-propylchromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL477528
PubChem CID 10339247
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 FSOGIJPGPZWNGO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H28O5/c1-6-8-14-11-16(23)27-22-17(14)20(25)15(10-9-12(3)4)21(26)18(22)19(24)13(5)7-2/h9,11,13,25-26H,6-8,10H2,1-5H3
SMILES CCCc1cc(=O)oc2c1c(O)c(CC=C(C)C)c(c2C(=O)C(CC)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.19 Volume:   397.451
?
Van der Waals volume.
Dense:   0.936 LogP:   4.762
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.773
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.779
?
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:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.438 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:   0.745 Fluc inhibitor:   0.019
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.943
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.678
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.26 Promiscuous compounds:   0.101

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.826 MDCK Permeability:   -4.71
Pgp-inhibitor:   0.967 Pgp-substrate:   0.165
PAMPA:   0.024
?
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):   0.018
20% Bioavailability (F20%):   0.61 30% Bioavailability (F30%):   0.861
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.118 MRP1:   0.993
Plasma Protein Binding (PPB):   97.15% Volume Distribution (VD):   0.116
Fu: 3.009%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.696
OATP1B3 inhibitor:   0.559 BCRP inhibitor:   0.798
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.933 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.176 CYP2C9-substrate:   0.837
CYP2D6-inhibitor:   0.02 CYP2D6-substrate:   0.041
CYP3A4-inhibitor:   0.958 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.72 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):  2.635 Half-life (T1/2):  1.116

ADMET: Toxicity

hERG Blockers:  0.092 hERG Blockers (10um):  0.53
Human Hepatotoxicity (H-HT):  0.58 Drug-induced Liver Injury (DILI):  0.564
AMES Toxicity:  0.217 Rat Oral Acute Toxicity:  0.537
Maximum Recommended Daily Dose:  0.626 Skin Sensitization:  0.757
Carcinogencity:  0.315 Eye Corrosion:  0.029
Eye Irritation:  0.716 Respiratory Toxicity:  0.902
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.418
Hematotoxicity:  0.367 Drug-induced Nephrotoxicity:  0.526
Genotoxicity:  0.263 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.357 Hek293 Cytotoxicity:  0.522
BCF:   1.861
?
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:   4.79
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.356
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.925
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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
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. stem n.a. PMID[11908963]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[12662094]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[15104480]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. leaf n.a. PMID[15340243]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25528 Calophyllum brasiliense Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25528 Calophyllum brasiliense 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
NPT80 Cell line Raji Homo sapiens Activity = 60.0 % PMID[15921411]
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[23501116]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 30100.0 nM PMID[32668302]
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[10924160]
NPT2 Others Unspecified n.a. Activity = 13.7 % PMID[24016834]
NPT2 Others Unspecified n.a. Activity = 50.6 % PMID[24045008]
NPT2 Others Unspecified n.a. Activity = 84.2 % PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 170.0 molar ratio DrugMatrix in vivo data: Biochemistry

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 NPC474624 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
1.0 High Similarity NPC131782
0.8814 High Similarity NPC219584
0.8167 Intermediate Similarity NPC183639
0.746 Intermediate Similarity NPC470909
0.7258 Intermediate Similarity NPC138047
0.7231 Intermediate Similarity NPC19476
0.7015 Intermediate Similarity NPC133060
0.7015 Intermediate Similarity NPC470556
0.6567 Remote Similarity NPC470083
0.6479 Remote Similarity NPC470554
0.6364 Remote Similarity NPC199458
0.6053 Remote Similarity NPC470553
0.6 Remote Similarity NPC188632
0.6 Remote Similarity NPC112791
0.5942 Remote Similarity NPC196586
0.5833 Remote Similarity NPC483432
0.5775 Remote Similarity NPC241975
0.5753 Remote Similarity NPC288910
0.5352 Remote Similarity NPC474939
0.5325 Remote Similarity NPC118059
0.5278 Remote Similarity NPC87609
0.52 Remote Similarity NPC470555
0.5195 Remote Similarity NPC33653
0.519 Remote Similarity NPC469935

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474624 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