Natural Product: NPC38153

Natural Product IDNPC38153
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Methoxy-2,2-Dimethyl-6-[(E)-2-Methylbut-2-Enoyl]-10-Propylpyrano[2,3-F]Chromen-8-One
IUPAC Name 5-methoxy-2,2-dimethyl-6-[(E)-2-methylbut-2-enoyl]-10-propylpyrano[2,3-f]chromen-8-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL478978
PubChem CID 11100998
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0003484] Pyranocoumarins
          • [CHEMONTID:0003485] Angular pyranocoumarins

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 RMUWCAYGHBNRQJ-MDWZMJQESA-N
Standard InCHI InChI=1S/C23H26O5/c1-7-9-14-12-16(24)27-22-17(14)21-15(10-11-23(4,5)28-21)20(26-6)18(22)19(25)13(3)8-2/h8,10-12H,7,9H2,1-6H3/b13-8+
SMILES CCCc1cc(=O)oc2c1c1c(C=CC(C)(C)O1)c(c2C(=O)/C(=C/C)/C)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.18 Volume:   403.554
?
Van der Waals volume.
Dense:   0.947 LogP:   4.301
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.787
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.385
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.409 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.294 Fsp3:   0.391
MCE-18:   45.375
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.472 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.768
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.73
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.295 Promiscuous compounds:   0.034

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.679 MDCK Permeability:   -4.634
Pgp-inhibitor:   0.883 Pgp-substrate:   0.001
PAMPA:   0.102
?
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):   0.004
20% Bioavailability (F20%):   0.877 30% Bioavailability (F30%):   0.97
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.996
Plasma Protein Binding (PPB):   98.851% Volume Distribution (VD):   0.241
Fu: 0.981%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.016
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.144 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.946 CYP2C19-substrate:   0.762
CYP2C9-inhibitor:   0.682 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.742
CYP3A4-inhibitor:   0.061 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.02 CYP2C8-inhibitor:   0.999
HLM stability:   0.969
?
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):  5.187 Half-life (T1/2):  0.663

ADMET: Toxicity

hERG Blockers:  0.174 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.729
AMES Toxicity:  0.367 Rat Oral Acute Toxicity:  0.445
Maximum Recommended Daily Dose:  0.791 Skin Sensitization:  0.624
Carcinogencity:  0.708 Eye Corrosion:  0.089
Eye Irritation:  0.814 Respiratory Toxicity:  0.857
Drug-induced Neurotoxicity:  0.267 Ototoxicity:  0.256
Hematotoxicity:  0.46 Drug-induced Nephrotoxicity:  0.339
Genotoxicity:  0.419 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.104 Hek293 Cytotoxicity:  0.432
BCF:   2.301
?
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:   4.656
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.826
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.226
?
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[19450986]
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[16643028]
NPT112 Cell line MOLT-4 Homo sapiens IC50 > 10000.0 nM PMID[22487595]
NPT6286 Cell line U1 Homo sapiens IC50 = 8440.0 nM PMID[22487595]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 3410.0 nM PMID[16472241]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 4320.0 nM DrugMatrix in vitro pharmacology data
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 3480.0 nM DrugMatrix in vitro pharmacology data
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[23265253]
NPT2 Others Unspecified n.a. Activity = 19.5 % PMID[15332854]
NPT2 Others Unspecified n.a. Activity = 62.5 % PMID[18579783]
NPT2 Others Unspecified n.a. Activity = 90.8 % PMID[16792425]
NPT2 Others Unspecified n.a. IC50 = 268.0 molar ratio DOI[10.6019/CHEMBL1201861]
NPT2 Others Unspecified n.a. Ratio IC50/EC50 > 2.93 n.a. PMID[22487595]
NPT2 Others Unspecified n.a. Ratio IC50/EC50 = 2.43 n.a. PMID[14698171]
NPT2 Others Unspecified n.a. Ratio IC50/EC50 = 1.95 n.a. PMID[24224862]

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 NPC38153 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
0.6944 Remote Similarity NPC201820
0.6176 Remote Similarity NPC268081
0.6104 Remote Similarity NPC139595
0.6104 Remote Similarity NPC60704
0.5974 Remote Similarity NPC141822
0.5974 Remote Similarity NPC1220
0.5974 Remote Similarity NPC205797
0.5974 Remote Similarity NPC142563
0.5974 Remote Similarity NPC241165
0.5875 Remote Similarity NPC293642
0.5375 Remote Similarity NPC180477
0.519 Remote Similarity NPC470555

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC38153 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
0.5974 Remote Similarity NPD5123 Phase 1
0.5974 Remote Similarity NPD5124 Phase 1

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