Natural Product: NPC174905

Natural Product IDNPC174905
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (9R,9's)-2,2',4,4',5,5'-Hexahydroxy-7,7'-Dimethyl-9,9'-Bianthracene-10,10'(9H,9'h)-Dione
IUPAC Name (10R)-1,3,8-trihydroxy-6-methyl-10-[(9S)-2,4,5-trihydroxy-7-methyl-10-oxo-9H-anthracen-9-yl]-10H-anthracen-9-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL518257
PubChem CID 12096289
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes

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 UUXPVUHOWQPCSC-PSWAGMNNSA-N
Standard InCHI InChI=1S/C30H22O8/c1-11-3-15-23(17-7-13(31)9-21(35)27(17)29(37)25(15)19(33)5-11)24-16-4-12(2)6-20(34)26(16)30(38)28-18(24)8-14(32)10-22(28)36/h3-10,23-24,31-36H,1-2H3/t23-,24+
SMILES Cc1cc(O)c2c(c1)[C@H](c1c(C2=O)c(O)cc(c1)O)[C@H]1c2cc(C)cc(c2C(=O)c2c1cc(O)cc2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   510.13 Volume:   509.509
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Van der Waals volume.
Dense:   1.001 LogP:   5.049
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.524
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -7.215
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   34.0
TPSA:   155.52
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   6.0 Rings:   6.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.217 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.67 Fsp3:   0.133
MCE-18:   118.471
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.983 Fluc inhibitor:   0.392
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.24
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.425
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.585 Promiscuous compounds:   0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.403 MDCK Permeability:   -4.819
Pgp-inhibitor:   0.122 Pgp-substrate:   0.763
PAMPA:   0.427
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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%):   0.159 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.926
Plasma Protein Binding (PPB):   94.859% Volume Distribution (VD):   0.016
Fu: 6.879%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.429
BSEP inhibitor:   0.618

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.042
CYP2C9-inhibitor:   0.777 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.997
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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):  0.569 Half-life (T1/2):  2.419

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.279
Human Hepatotoxicity (H-HT):  0.98 Drug-induced Liver Injury (DILI):  0.427
AMES Toxicity:  0.994 Rat Oral Acute Toxicity:  0.378
Maximum Recommended Daily Dose:  0.593 Skin Sensitization:  0.985
Carcinogencity:  0.556 Eye Corrosion:  0.0
Eye Irritation:  0.998 Respiratory Toxicity:  0.527
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.667
Hematotoxicity:  0.637 Drug-induced Nephrotoxicity:  0.853
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.271
A549 Cytotoxicity:  0.89 Hek293 Cytotoxicity:  0.982
BCF:   1.976
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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:   4.998
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.894
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.38
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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
NPO32935 rhamnus nepalensis Species Rhamnaceae Eukaryota Leaves Pa Co, Mai Chau, Hoa Binh Province, 150 km west of Hanoi, Vietnam 1995-Nov PMID[11575949]

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
NPT91 Cell line KB Homo sapiens IC50 = 1100.0 nM PMID[20515062]
NPT65 Cell line HepG2 Homo sapiens EC50 = 13800.0 nM PMID[37276438]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum EC50 = 1650.0 nM PMID[37276438]
NPT29309 Organism Mycoplasma genitalium Mycoplasma genitalium EC50 > 10000.0 nM PMID[37276438]
NPT1022 Organism Cryptosporidium parvum Cryptosporidium parvum EC50 > 7200.0 nM PMID[37276438]
NPT1019 Organism Trichomonas vaginalis Trichomonas vaginalis EC50 > 10000.0 nM PMID[37276438]

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 NPC174905 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 NPC293545
0.8095 Intermediate Similarity NPC474203
0.8095 Intermediate Similarity NPC313047
0.8095 Intermediate Similarity NPC451542
0.8095 Intermediate Similarity NPC295712
0.6429 Remote Similarity NPC161964
0.6429 Remote Similarity NPC287604
0.6098 Remote Similarity NPC254847
0.5814 Remote Similarity NPC267205
0.5472 Remote Similarity NPC477221
0.5294 Remote Similarity NPC601142
0.5294 Remote Similarity NPC601530
0.5294 Remote Similarity NPC606267
0.5294 Remote Similarity NPC610829
0.5185 Remote Similarity NPC600622
0.5088 Remote Similarity NPC600612
0.5075 Remote Similarity NPC600427
0.5075 Remote Similarity NPC607712

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC174905 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
0.6098 Remote Similarity NPD1509 Clinical (unspecified phase)

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