Natural Product: NPC494981

Natural Product IDNPC494981
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (5~{R},5~{a}~{R},8~{a}~{R},9~{S})-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5~{a},6,8~{a},9-tetrahydro-5~{H}-isobenzofuro[5,6-f][1,3]benzodioxol-8-one
IUPAC Name (5~{R},5~{a}~{R},8~{a}~{R},9~{S})-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5~{a},6,8~{a},9-tetrahydro-5~{H}-isobenzofuro[5,6-f][1,3]benzodioxol-8-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 YJGVMLPVUAXIQN-KJYZGMDISA-N
Standard InCHI InChI=1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18-,19-,20-/m0/s1
SMILES COC1=CC([C@H]2C3=CC4=C(C=C3[C@H](O)[C@H]3COC(=O)[C@H]23)OCO4)=CC(OC)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   414.13 Volume:   398.152
?
Van der Waals volume.
Dense:   1.04 LogP:   1.829
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.118
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.612
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   26.0
TPSA:   92.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.763 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.752 Fsp3:   0.409
MCE-18:   94.839
?
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:   0.388 Fluc inhibitor:   0.093
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.188
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.07
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.063 Promiscuous compounds:   0.912

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.152 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.12 Pgp-substrate:   0.01
PAMPA:   0.278
?
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%):   0.01 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.495

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.919 MRP1:   0.994
Plasma Protein Binding (PPB):   98.049% Volume Distribution (VD):   -0.276
Fu: 2.19%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.948
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.055
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.984 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.913
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.588
?
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):  4.562 Half-life (T1/2):  2.271

ADMET: Toxicity

hERG Blockers:  0.148 hERG Blockers (10um):  0.626
Human Hepatotoxicity (H-HT):  0.814 Drug-induced Liver Injury (DILI):  0.978
AMES Toxicity:  0.796 Rat Oral Acute Toxicity:  0.61
Maximum Recommended Daily Dose:  0.714 Skin Sensitization:  0.961
Carcinogencity:  0.83 Eye Corrosion:  0.0
Eye Irritation:  0.278 Respiratory Toxicity:  0.807
Drug-induced Neurotoxicity:  0.851 Ototoxicity:  0.758
Hematotoxicity:  0.811 Drug-induced Nephrotoxicity:  0.961
Genotoxicity:  0.968 RPMI-8226 Immunitoxicity:  0.442
A549 Cytotoxicity:  0.852 Hek293 Cytotoxicity:  0.546
BCF:   1.165
?
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:   3.648
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.73
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.524
?
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
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. root n.a. PMID[10230514]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[12956064]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[16933860]
NPO14752 Sinopodophyllum emodi Species Berberidaceae Eukaryota roots and rhizomes n.a. n.a. PMID[21570846]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25608854]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[26359402]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[34203980]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[37894884]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[38263385]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[39345860]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[6253598]
NPO17947 Hyptis verticillata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[8277312]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. root n.a. Database[Article]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14752 Sinopodophyllum emodi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5200 Diphylleia grayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18306 Juniperus thurifera Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16616 Juniperus virginiana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60503 Polygala polygama Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45242 Podophyllum pleianthum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52168 Podophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47362 Podophyllum emodi Wall Genus Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2333 Micranthemum umbrosum Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53345 Linum mucronatum ssp. armenum Genus Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56847 Linum flavum var. compactum Genus Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23357 Linum catharticum Species Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51211 Linum boissieri Genus Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3158 Linum album Species Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11328 Juniperus chinensis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47198 Hugonia tomentosa Genus Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31167 Dysosma veitchii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30046 Dysosma majorensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26868 Diphylleia sinensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17947 Hyptis verticillata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31167 Dysosma veitchii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17947 Hyptis verticillata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3158 Linum album Species Linaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26868 Diphylleia sinensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30046 Dysosma majorensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5200 Diphylleia grayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18306 Juniperus thurifera Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16616 Juniperus virginiana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11328 Juniperus chinensis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18306 Juniperus thurifera Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26868 Diphylleia sinensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16616 Juniperus virginiana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3158 Linum album Species Linaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17947 Hyptis verticillata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5200 Diphylleia grayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26868 Diphylleia sinensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5200 Diphylleia grayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3158 Linum album Species Linaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23848 Podophyllum peltatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5200 Diphylleia grayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14752 Sinopodophyllum emodi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2333 Micranthemum umbrosum Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11328 Juniperus chinensis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1576 Anthriscus sylvestris Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18306 Juniperus thurifera Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16616 Juniperus virginiana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3158 Linum album Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17947 Hyptis verticillata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23357 Linum catharticum Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23682 Juniperus phoenicea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26868 Diphylleia sinensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23848 Podophyllum peltatum Species Berberidaceae 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

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 NPC494981 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 NPC237946
1.0 High Similarity NPC32373
0.8947 High Similarity NPC119910
0.8136 Intermediate Similarity NPC91634
0.8136 Intermediate Similarity NPC150943
0.8136 Intermediate Similarity NPC268718
0.7667 Intermediate Similarity NPC207584
0.7667 Intermediate Similarity NPC19947
0.6885 Remote Similarity NPC178574
0.6769 Remote Similarity NPC288149
0.6557 Remote Similarity NPC239890
0.6557 Remote Similarity NPC209411
0.619 Remote Similarity NPC80230
0.619 Remote Similarity NPC104024
0.619 Remote Similarity NPC101755
0.619 Remote Similarity NPC304687
0.619 Remote Similarity NPC65574
0.5846 Remote Similarity NPC262455
0.5846 Remote Similarity NPC177476
0.5821 Remote Similarity NPC210642
0.5821 Remote Similarity NPC13985
0.5758 Remote Similarity NPC149505
0.5606 Remote Similarity NPC65591
0.5571 Remote Similarity NPC115281
0.5556 Remote Similarity NPC477698
0.5522 Remote Similarity NPC480477
0.5397 Remote Similarity NPC164082
0.5246 Remote Similarity NPC151423
0.5143 Remote Similarity NPC30009
0.5143 Remote Similarity NPC103197
0.5082 Remote Similarity NPC218841
0.5062 Remote Similarity NPC152424

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC494981 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
1.0 High Similarity NPD4965 Approved
1.0 High Similarity NPD4966 Phase 4
1.0 High Similarity NPD4967 Phase 2
0.7429 Intermediate Similarity NPD37 Approved

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