Natural Product: NPC60389

Natural Product IDNPC60389
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Mollugin
IUPAC Name methyl 6-hydroxy-2,2-dimethylbenzo[h]chromene-5-carboxylate
Synonyms Mollugin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL446008
PubChem CID 124219
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001640] Naphthopyrans

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 VLGATXOTCNBWIT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O4/c1-17(2)9-8-12-13(16(19)20-3)14(18)10-6-4-5-7-11(10)15(12)21-17/h4-9,18H,1-3H3
SMILES COC(=O)c1c2C=CC(Oc2c2c(c1O)cccc2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   293.625
?
Van der Waals volume.
Dense:   0.968 LogP:   4.115
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.708
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.868
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.814 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.559 Fsp3:   0.235
MCE-18:   39.81
?
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:   0.227 Fluc inhibitor:   0.108
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.686
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.507
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.542 Promiscuous compounds:   0.163

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.945 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.805 Pgp-substrate:   0.045
PAMPA:   0.347
?
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):   0.027
20% Bioavailability (F20%):   0.245 30% Bioavailability (F30%):   0.791
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.688 MRP1:   0.96
Plasma Protein Binding (PPB):   98.619% Volume Distribution (VD):   -0.243
Fu: 0.903%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.967 BCRP inhibitor:   0.446
BSEP inhibitor:   0.981

ADMET: Metabolism

CYP1A2-inhibitor:   0.063 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.528 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.715 CYP2C9-substrate:   0.021
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.32
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.012 CYP2C8-inhibitor:   0.769
HLM stability:   0.992
?
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):  3.196 Half-life (T1/2):  1.077

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.534
Human Hepatotoxicity (H-HT):  0.476 Drug-induced Liver Injury (DILI):  0.438
AMES Toxicity:  0.677 Rat Oral Acute Toxicity:  0.419
Maximum Recommended Daily Dose:  0.499 Skin Sensitization:  0.777
Carcinogencity:  0.668 Eye Corrosion:  0.296
Eye Irritation:  0.979 Respiratory Toxicity:  0.81
Drug-induced Neurotoxicity:  0.369 Ototoxicity:  0.261
Hematotoxicity:  0.234 Drug-induced Nephrotoxicity:  0.319
Genotoxicity:  0.171 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.092 Hek293 Cytotoxicity:  0.22
BCF:   1.564
?
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:   4.343
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.857
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.342
?
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
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0168-1656(02)00067-6]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[18078747]
NPO28159 Rubia akane Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[8176404]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[8882438]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. amniotic fluid n.a. Database[Article]
NPO2784 Radix rubiae Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28159 Rubia akane Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23286 Galium mollugo Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16243 Rubia schumannina Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23286 Galium mollugo Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16243 Rubia schumannina Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2784 Radix rubiae Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23286 Galium mollugo Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28159 Rubia akane Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23286 Galium mollugo Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28159 Rubia akane Species Rubiaceae 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
NPT5847 Individual protein NAD-dependent protein deacetylase sirtuin-6 Homo sapiens EC1.5 = 227.5 uM PMID[32787077]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28833 No target No relevant target n.a. IC50 = 0.7 ug.mL-1 PMID[32721784]
NPT963 Organism Hepatitis B virus Hepatitis B virus IC50 = 2.0 ug.mL-1 PMID[8882438]
NPT20967 Cell line Platelet n.a. Activity = 90.9 % PMID[8176404]
NPT20967 Cell line Platelet n.a. Activity = 0.0 % PMID[8176404]
NPT20967 Cell line Platelet n.a. Activity = 34.1 % PMID[8176404]
NPT20967 Cell line Platelet n.a. Activity = 62.5 % PMID[8176404]

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 NPC60389 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
0.5965 Remote Similarity NPC485258
0.5763 Remote Similarity NPC211565
0.5645 Remote Similarity NPC485260
0.5536 Remote Similarity NPC71372
0.5238 Remote Similarity NPC485259

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC60389 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