Natural Product: NPC302783

Natural Product IDNPC302783
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Obtusifolin
IUPAC Name 2,8-dihydroxy-1-methoxy-3-methylanthracene-9,10-dione
Synonyms Obtusifolin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL448400
PubChem CID 3083575
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0000151] Anthraquinones
          • [CHEMONTID:0001598] Hydroxyanthraquinones

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 NYRXUBDGDSRBGB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O5/c1-7-6-9-12(16(21-2)13(7)18)15(20)11-8(14(9)19)4-3-5-10(11)17/h3-6,17-18H,1-2H3
SMILES Cc1cc2c(C(=O)c3c(cccc3O)C2=O)c(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
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Van der Waals volume.
Dense:   1.006 LogP:   3.5
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.022
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.256
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   83.83
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.715 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.38 Fsp3:   0.125
MCE-18:   38.0
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.274 Fluc inhibitor:   0.271
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.262
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.536
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.461 Promiscuous compounds:   0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.97 MDCK Permeability:   -4.81
Pgp-inhibitor:   0.956 Pgp-substrate:   0.103
PAMPA:   0.657
?
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):   0.233
20% Bioavailability (F20%):   0.097 30% Bioavailability (F30%):   0.67
50% Bioavailability (F50%):   0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.875
Plasma Protein Binding (PPB):   97.354% Volume Distribution (VD):   -0.03
Fu: 2.146%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.419
BSEP inhibitor:   0.637

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.015
CYP2C19-inhibitor:   0.228 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.019 CYP2C9-substrate:   0.055
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.496
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.05
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.753
HLM stability:   0.357
?
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):  4.598 Half-life (T1/2):  1.011

ADMET: Toxicity

hERG Blockers:  0.057 hERG Blockers (10um):  0.522
Human Hepatotoxicity (H-HT):  0.628 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.902 Rat Oral Acute Toxicity:  0.556
Maximum Recommended Daily Dose:  0.382 Skin Sensitization:  0.908
Carcinogencity:  0.82 Eye Corrosion:  0.001
Eye Irritation:  0.967 Respiratory Toxicity:  0.839
Drug-induced Neurotoxicity:  0.378 Ototoxicity:  0.361
Hematotoxicity:  0.773 Drug-induced Nephrotoxicity:  0.599
Genotoxicity:  0.854 RPMI-8226 Immunitoxicity:  0.283
A549 Cytotoxicity:  0.822 Hek293 Cytotoxicity:  0.463
BCF:   1.495
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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:   3.955
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.102
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.409
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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
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.lwt.2014.11.023]
NPO8921 Senna obtusifolia Species Fabaceae Eukaryota Seeds n.a. n.a. PMID[2213033]
NPO31136 Cassia tora Species Fabaceae Eukaryota seeds n.a. n.a. PMID[26483136]
NPO8921 Senna obtusifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7672 Senna tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7672 Senna tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8921 Senna obtusifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8921 Senna obtusifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7672 Senna tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7672 Senna tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8921 Senna obtusifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17774 Hemerocallis fulva Species Xanthorrhoeaceae 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
NPT862 Individual protein Epoxide hydratase Homo sapiens Inhibition = 2.6 % PMID[26483136]

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[18556196]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.25 mg/ml PMID[2213033]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity > 0.25 mg/ml PMID[2213033]
NPT2 Others Unspecified n.a. Activity = 4.3 % PMID[18556196]
NPT2 Others Unspecified n.a. Activity = 27.8 % PMID[18556196]
NPT2 Others Unspecified n.a. Activity = 54.9 % PMID[18556196]
NPT2 Others Unspecified n.a. Activity = 98.7 % PMID[18556196]

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 NPC302783 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
0.7174 Intermediate Similarity NPC473201
0.6667 Remote Similarity NPC14561
0.6667 Remote Similarity NPC1268
0.6458 Remote Similarity NPC5379
0.6458 Remote Similarity NPC37543
0.58 Remote Similarity NPC199463
0.5745 Remote Similarity NPC416
0.561 Remote Similarity NPC103540
0.5556 Remote Similarity NPC604340
0.549 Remote Similarity NPC124365
0.5366 Remote Similarity NPC375356
0.5349 Remote Similarity NPC300274
0.5208 Remote Similarity NPC282923
0.5102 Remote Similarity NPC205992

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC302783 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
0.561 Remote Similarity NPD1470 Phase 4

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