Natural Product: NPC375356

Natural Product IDNPC375356
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Anthrarufin
IUPAC Name 1,5-dihydroxyanthracene-9,10-dione
Synonyms 1,5-Dihydroxy-Anthraquinone; Anthrarufin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL55761
PubChem CID 8328
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0000151] Anthraquinones

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 JPICKYUTICNNNJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H8O4/c15-9-5-1-3-7-11(9)14(18)8-4-2-6-10(16)12(8)13(7)17/h1-6,15-16H
SMILES c1cc2c(c(c1)O)C(=O)c1cccc(c1C2=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   240.04 Volume:   239.1
?
Van der Waals volume.
Dense:   1.004 LogP:   3.585
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.244
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.588
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.629 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.037 Fsp3:   0.0
MCE-18:   34.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.272 Fluc inhibitor:   0.573
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.423
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.141
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.932 Promiscuous compounds:   0.441

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.731 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.894 Pgp-substrate:   0.176
PAMPA:   0.702
?
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):   0.403
20% Bioavailability (F20%):   0.027 30% Bioavailability (F30%):   0.867
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.219
Plasma Protein Binding (PPB):   94.568% Volume Distribution (VD):   0.354
Fu: 7.304%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.554
BSEP inhibitor:   0.327

ADMET: Metabolism

CYP1A2-inhibitor:   0.958 CYP1A2-substrate:   0.328
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.093 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.157
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.159
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.975
HLM stability:   0.771
?
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):  1.344 Half-life (T1/2):  1.367

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.528
Human Hepatotoxicity (H-HT):  0.555 Drug-induced Liver Injury (DILI):  0.867
AMES Toxicity:  0.916 Rat Oral Acute Toxicity:  0.525
Maximum Recommended Daily Dose:  0.266 Skin Sensitization:  0.944
Carcinogencity:  0.778 Eye Corrosion:  0.006
Eye Irritation:  0.986 Respiratory Toxicity:  0.917
Drug-induced Neurotoxicity:  0.2 Ototoxicity:  0.284
Hematotoxicity:  0.658 Drug-induced Nephrotoxicity:  0.542
Genotoxicity:  0.834 RPMI-8226 Immunitoxicity:  0.259
A549 Cytotoxicity:  0.866 Hek293 Cytotoxicity:  0.461
BCF:   2.136
?
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:   4.231
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.977
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.456
?
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
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[11076555]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[11459643]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[1517743]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[8277318]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11391 Polygonum cuspidatum Species Polygonaceae 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
NPT261 Individual protein Monoamine oxidase A Homo sapiens IC50 = 30800.0 nM PMID[34915314]
NPT582 Individual protein Monoamine oxidase B Homo sapiens Inhibition n.a. n.a. % PMID[34915314]
NPT77 Individual protein Transthyretin Homo sapiens IC50 > 100000.0 nM PMID[34225167]
NPT901 Individual protein UDP-glucuronosyltransferase 1-1 Homo sapiens Activity = 0.0 pm/min/mg PMID[20421404]
NPT544 Protein family Estrogen receptor Homo sapiens Control = 105.7 % PMID[11459643]
NPT544 Protein family Estrogen receptor Homo sapiens Control = 107.0 % PMID[11459643]
NPT544 Protein family Estrogen receptor Homo sapiens Control = 113.9 % PMID[11459643]

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 > 80.0 % PMID[18426954]
NPT80 Cell line Raji Homo sapiens Activity = 70.0 % PMID[22487595]
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 100000.0 nM PMID[12398531]
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 100000.0 nM PMID[18077363]
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 100000.0 nM PMID[25599834]
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 100000.0 nM PMID[18955526]
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 100000.0 nM PMID[23558238]
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vivo data: Pathology
NPT111 Cell line K562 Homo sapiens GI50 n.a. 100000.0 nM PMID[8289059]
NPT376 Cell line A498 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 100000.0 nM PMID[19265439]
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 100000.0 nM PMID[20933416]
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 100000.0 nM PMID[19721074]
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 100000.0 nM PMID[22742761]
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 100000.0 nM PMID[15620264]
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vitro pharmacology data
NPT572 Cell line DMS-273 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vivo data: Pathology
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 100000.0 nM PMID[10465531]
NPT385 Cell line SR Homo sapiens GI50 n.a. 100000.0 nM PMID[18163588]
NPT573 Cell line M19-MEL Homo sapiens GI50 n.a. 100000.0 nM PMID[18500841]
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 100000.0 nM PMID[3735324]
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 100000.0 nM PMID[16643028]
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 100000.0 nM PMID[26034885]
NPT387 Cell line M14 Homo sapiens GI50 n.a. 100000.0 nM PMID[24763261]
NPT574 Cell line XF498 Homo sapiens GI50 n.a. 100000.0 nM DOI[10.1007/s00044-011-9708-z]
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 100000.0 nM PMID[20022253]
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 100000.0 nM PMID[20155971]
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 100000.0 nM PMID[8021914]
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 100000.0 nM PMID[20421404]
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 100000.0 nM PMID[10514305]
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 100000.0 nM PMID[20805010]
NPT81 Cell line A549 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vivo data: Hematology
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 100000.0 nM PMID[21341710]
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 100000.0 nM PMID[17420206]
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 100000.0 nM PMID[16038556]
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 100000.0 nM Open TG-GATES in vivo data: Organ Weight
NPT731 Cell line LXFL 529 Homo sapiens GI50 n.a. 100000.0 nM PMID[25499431]
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 100000.0 nM PMID[1336040]
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 100000.0 nM PMID[9358638]
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vitro pharmacology data
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 100000.0 nM PMID[17220425]
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 100000.0 nM PMID[22946634]
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 100000.0 nM PMID[9677274]
NPT578 Cell line SNB-78 Homo sapiens GI50 n.a. 100000.0 nM DrugMatrix in vitro pharmacology data
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 100000.0 nM PMID[9514013]
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT579 Cell line DLD-1 Homo sapiens GI50 n.a. 100000.0 nM PMID[17665951]
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 100000.0 nM PMID[19349516]
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 100000.0 nM PMID[23149227]
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 100000.0 nM DOI[10.6019/CHEMBL1201861]
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 100000.0 nM PMID[17698618]
NPT762 Cell line A-431 Homo sapiens Activity n.a. n.a. n.a. PMID[34995690]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 > 1000.0 nM PMID[12646019]
NPT1365 Organism Trichoplusia ni Trichoplusia ni FDI = -58.6 % DOI[10.1016/j.cropro.2011.09.009]
NPT2 Others Unspecified n.a. Activity < 50.0 % PMID[23634786]
NPT2 Others Unspecified n.a. Inhibition = 100.0 % PMID[20429578]
NPT2 Others Unspecified n.a. Inhibition = 92.3 % PubChem BioAssay data set
NPT2 Others Unspecified n.a. Inhibition = 70.1 % PMID[15974580]
NPT2 Others Unspecified n.a. Inhibition = 27.1 % PMID[21377771]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1365 Organism Trichoplusia ni Trichoplusia ni mortality = 15.0 % DOI[10.1016/j.cropro.2011.09.009]





 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 NPC375356 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
0.8846 High Similarity NPC300274
0.8846 High Similarity NPC608834
0.88 High Similarity NPC103540
0.7097 Intermediate Similarity NPC604340
0.7037 Intermediate Similarity NPC96915
0.6765 Remote Similarity NPC199253
0.6765 Remote Similarity NPC205992
0.6667 Remote Similarity NPC99731
0.6471 Remote Similarity NPC282923
0.6286 Remote Similarity NPC416
0.6111 Remote Similarity NPC70622
0.6053 Remote Similarity NPC21599
0.5946 Remote Similarity NPC487321
0.5938 Remote Similarity NPC142956
0.5789 Remote Similarity NPC257644
0.5758 Remote Similarity NPC294226
0.575 Remote Similarity NPC474813
0.5641 Remote Similarity NPC288089
0.5641 Remote Similarity NPC604901
0.5641 Remote Similarity NPC608971
0.561 Remote Similarity NPC255641
0.561 Remote Similarity NPC37220
0.5588 Remote Similarity NPC31799
0.55 Remote Similarity NPC124365
0.5476 Remote Similarity NPC242994
0.5476 Remote Similarity NPC605722
0.5455 Remote Similarity NPC147418
0.5366 Remote Similarity NPC1268
0.5366 Remote Similarity NPC302783
0.5349 Remote Similarity NPC169452
0.5349 Remote Similarity NPC193555
0.5349 Remote Similarity NPC245923
0.5349 Remote Similarity NPC272268
0.5294 Remote Similarity NPC44437
0.5238 Remote Similarity NPC66593
0.5238 Remote Similarity NPC606400
0.5227 Remote Similarity NPC225051
0.5227 Remote Similarity NPC205982
0.5172 Remote Similarity NPC224584
0.5143 Remote Similarity NPC608942
0.5135 Remote Similarity NPC607416
0.5122 Remote Similarity NPC252208
0.5122 Remote Similarity NPC226578
0.5116 Remote Similarity NPC610494
0.5111 Remote Similarity NPC61531
0.5111 Remote Similarity NPC79627
0.5111 Remote Similarity NPC181560
0.5111 Remote Similarity NPC80035

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC375356 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
0.88 High Similarity NPD1470 Phase 4
0.5806 Remote Similarity NPD1201 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