Natural Product: NPC226862

Natural Product IDNPC226862
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Calopiptin
IUPAC Name 5-[(2S,3S,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyloxolan-2-yl]-1,3-benzodioxole
Synonyms Calopiptin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL469499
PubChem CID 12302265
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 HSMDOSKNXLVXIP-IRTBSJMASA-N
Standard InCHI InChI=1S/C21H24O5/c1-12-13(2)21(15-6-8-17-19(10-15)25-11-24-17)26-20(12)14-5-7-16(22-3)18(9-14)23-4/h5-10,12-13,20-21H,11H2,1-4H3/t12-,13-,20+,21-/m0/s1
SMILES C[C@H]1[C@H](C)[C@@H](c2ccc3c(c2)OCO3)O[C@H]1c1ccc(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.16 Volume:   365.679
?
Van der Waals volume.
Dense:   0.974 LogP:   2.659
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.882
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.369
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.806 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.369 Fsp3:   0.429
MCE-18:   73.333
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.372 Fluc inhibitor:   0.878
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.018
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.286 Promiscuous compounds:   0.167

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.968 MDCK Permeability:   -4.736
Pgp-inhibitor:   0.769 Pgp-substrate:   0.017
PAMPA:   0.048
?
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):   0.0
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.291

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.813 MRP1:   0.896
Plasma Protein Binding (PPB):   95.103% Volume Distribution (VD):   0.257
Fu: 4.625%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.858
OATP1B3 inhibitor:   0.905 BCRP inhibitor:   0.184
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.846
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.988
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.043 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.086
HLM stability:   0.067
?
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):  7.089 Half-life (T1/2):  1.317

ADMET: Toxicity

hERG Blockers:  0.249 hERG Blockers (10um):  0.451
Human Hepatotoxicity (H-HT):  0.793 Drug-induced Liver Injury (DILI):  0.933
AMES Toxicity:  0.711 Rat Oral Acute Toxicity:  0.437
Maximum Recommended Daily Dose:  0.335 Skin Sensitization:  0.511
Carcinogencity:  0.842 Eye Corrosion:  0.121
Eye Irritation:  0.85 Respiratory Toxicity:  0.818
Drug-induced Neurotoxicity:  0.66 Ototoxicity:  0.338
Hematotoxicity:  0.684 Drug-induced Nephrotoxicity:  0.561
Genotoxicity:  0.723 RPMI-8226 Immunitoxicity:  0.183
A549 Cytotoxicity:  0.459 Hek293 Cytotoxicity:  0.512
BCF:   2.277
?
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:   3.876
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.631
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.839
?
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
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[14738383]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[15324487]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. leaf n.a. PMID[26184150]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3739 Nectandra megapotamica Species Lauraceae 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
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 21.4 % PMID[11141110]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 49.2 % PMID[11141110]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 60.3 % PMID[24370114]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 12600.0 nM PMID[18183025]

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 NPC226862 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 NPC57119
1.0 High Similarity NPC158471
0.8919 High Similarity NPC271208
0.8919 High Similarity NPC233224
0.8919 High Similarity NPC610263
0.8333 Intermediate Similarity NPC136750
0.8333 Intermediate Similarity NPC266848
0.8108 Intermediate Similarity NPC216929
0.8108 Intermediate Similarity NPC312713
0.8108 Intermediate Similarity NPC126935
0.8108 Intermediate Similarity NPC65933
0.8108 Intermediate Similarity NPC57268
0.8108 Intermediate Similarity NPC172676
0.7447 Intermediate Similarity NPC135777
0.7447 Intermediate Similarity NPC7744
0.7317 Intermediate Similarity NPC50683
0.7317 Intermediate Similarity NPC112571
0.7317 Intermediate Similarity NPC285725
0.7292 Intermediate Similarity NPC142547
0.7292 Intermediate Similarity NPC228469
0.7292 Intermediate Similarity NPC488984
0.7292 Intermediate Similarity NPC488985
0.7115 Intermediate Similarity NPC302506
0.7115 Intermediate Similarity NPC241846
0.7115 Intermediate Similarity NPC93610
0.7111 Intermediate Similarity NPC487685
0.6923 Remote Similarity NPC179521
0.6889 Remote Similarity NPC227160
0.6889 Remote Similarity NPC82111
0.6889 Remote Similarity NPC483654
0.6667 Remote Similarity NPC31530
0.6591 Remote Similarity NPC480478
0.6522 Remote Similarity NPC158331
0.6512 Remote Similarity NPC72046
0.6512 Remote Similarity NPC261812
0.6512 Remote Similarity NPC65183
0.6383 Remote Similarity NPC487684
0.6275 Remote Similarity NPC24257
0.6275 Remote Similarity NPC153620
0.625 Remote Similarity NPC11258
0.625 Remote Similarity NPC21867
0.625 Remote Similarity NPC45774
0.625 Remote Similarity NPC74914
0.6 Remote Similarity NPC171928
0.6 Remote Similarity NPC158526
0.6 Remote Similarity NPC129687
0.6 Remote Similarity NPC33611
0.6 Remote Similarity NPC16830
0.6 Remote Similarity NPC100223
0.5918 Remote Similarity NPC189474
0.5902 Remote Similarity NPC226153
0.5862 Remote Similarity NPC487682
0.5849 Remote Similarity NPC483653
0.5806 Remote Similarity NPC304048
0.5769 Remote Similarity NPC260842
0.5769 Remote Similarity NPC93783
0.5769 Remote Similarity NPC320380
0.561 Remote Similarity NPC9891
0.561 Remote Similarity NPC88297
0.561 Remote Similarity NPC186845
0.5577 Remote Similarity NPC165128
0.5435 Remote Similarity NPC344161
0.537 Remote Similarity NPC298317
0.537 Remote Similarity NPC255566
0.5345 Remote Similarity NPC600032
0.5333 Remote Similarity NPC121783
0.5333 Remote Similarity NPC34902
0.5333 Remote Similarity NPC18449
0.5333 Remote Similarity NPC308555
0.5283 Remote Similarity NPC177868
0.5273 Remote Similarity NPC474139
0.5208 Remote Similarity NPC474295
0.5179 Remote Similarity NPC88640
0.5179 Remote Similarity NPC101153
0.5179 Remote Similarity NPC193666
0.5179 Remote Similarity NPC123526
0.5179 Remote Similarity NPC608725
0.5094 Remote Similarity NPC14022
0.5094 Remote Similarity NPC601703
0.5085 Remote Similarity NPC43514

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC226862 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