NPASS Compound

Natural Product: NPC112504

Natural Product ID	NPC112504
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HSWIRQIYASIOBE-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	318730
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

RDKit 3D 51 54 0 0 0 0 0 0 0 0999 V2000 7.4635 0.6589 -1.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9879 0.5487 -0.8772 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4599 -0.0626 0.2409 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1080 -0.1911 0.4740 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2401 0.3178 -0.4591 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7364 0.9440 -1.6046 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0995 1.0542 -1.8039 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8341 1.4485 -2.5294 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8075 0.2019 -0.2493 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0288 0.6755 -1.1174 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2299 -0.4398 0.9245 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1161 -0.9506 1.8609 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6289 -1.5702 2.9944 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2811 -1.6637 3.1634 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6012 -1.1458 2.2139 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1356 -0.5272 1.0823 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9548 -0.0056 0.1263 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3540 0.0152 0.0860 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7799 -0.8297 -1.0941 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2593 -0.9845 -1.2013 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8993 0.1590 -0.4268 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0372 1.3803 -0.6769 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8331 2.6220 -0.3584 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0136 2.5535 -1.1261 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8490 1.3118 0.0066 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0546 -0.1293 0.9112 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7344 -2.2206 -0.8083 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2273 -2.0989 -0.9023 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2002 -2.2920 4.3127 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5711 -0.8412 1.6631 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3886 -1.2988 2.5020 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6480 0.6006 -2.1665 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9861 -0.1251 -0.5002 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7928 1.6717 -0.7605 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1445 -0.4685 0.9850 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5097 1.5340 -2.6815 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5991 2.4282 -2.4877 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3488 -1.9638 3.7160 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6416 -1.2734 2.4459 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7449 -0.4775 0.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3599 -0.4475 -2.0528 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5818 -0.8275 -2.2721 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9264 0.3570 -0.8337 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8108 1.3909 -1.7642 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3034 3.5222 -0.6868 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1532 2.6508 0.6993 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8968 2.9686 -2.0159 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0742 -1.1214 1.0957 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8938 -2.8312 -1.5700 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6298 -2.3693 -1.6256 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0602 -1.8588 5.2382 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 6 8 1 0 5 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 21 26 1 0 20 27 1 0 19 28 1 0 14 29 1 0 12 30 1 0 30 31 2 0 7 2 1 0 16 11 1 0 25 18 1 0 30 4 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 7 36 1 0 8 37 1 0 13 38 1 0 15 39 1 0 18 40 1 0 19 41 1 0 20 42 1 0 21 43 1 0 22 44 1 0 23 45 1 0 23 46 1 0 24 47 1 0 26 48 1 0 27 49 1 0 28 50 1 0 29 51 1 0 M END

Standard InCHIKey	HSWIRQIYASIOBE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H20O10/c1-7-2-9-14(11(24)3-7)18(27)15-10(16(9)25)4-8(23)5-12(15)30-21-20(29)19(28)17(26)13(6-22)31-21/h2-5,13,17,19-24,26,28-29H,6H2,1H3
SMILES	Cc1cc2c(c(c1)O)C(=O)c1c(cc(cc1OC1C(C(C(C(CO)O1)O)O)O)O)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.11	Volume:	404.357 ? Van der Waals volume.
Dense:	1.069	LogP:	0.835 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.552 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.138 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	173.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.312	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.936	Fsp³:	0.333
MCE-18:	90.643 ? 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:	1
Colloidal aggregators:	0.131	Fluc inhibitor:	0.035 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.354 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.843 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.203	Promiscuous compounds:	0.405

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.211	MDCK Permeability:	-5.185
Pgp-inhibitor:	0.0	Pgp-substrate:	0.368
PAMPA:	0.999 ? 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):	0.792
20% Bioavailability (F20%):	0.536	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.91
Plasma Protein Binding (PPB):	85.185%	Volume Distribution (VD):	0.182
Fu:	14.486% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.026
OATP1B3 inhibitor:	0.91	BCRP inhibitor:	0.031
BSEP inhibitor:	0.008

ADMET: Metabolism

CYP1A2-inhibitor:	0.063	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.355	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.023	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.026 ? 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):

2.917

Half-life (T1/2):

2.439

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.43
Human Hepatotoxicity (H-HT):	0.725	Drug-induced Liver Injury (DILI):	0.85
AMES Toxicity:	0.887	Rat Oral Acute Toxicity:	0.313
Maximum Recommended Daily Dose:	0.237	Skin Sensitization:	0.622
Carcinogencity:	0.565	Eye Corrosion:	0.0
Eye Irritation:	0.456	Respiratory Toxicity:	0.245
Drug-induced Neurotoxicity:	0.159	Ototoxicity:	0.908
Hematotoxicity:	0.391	Drug-induced Nephrotoxicity:	0.298
Genotoxicity:	0.767	RPMI-8226 Immunitoxicity:	0.23
A549 Cytotoxicity:	0.632	Hek293 Cytotoxicity:	0.688
BCF:	0.774 ? 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:	3.349 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.86 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.987 ? 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

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

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 NPC112504 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	18347
0.1-0.2	27108
0.2-0.3	3547
0.3-0.4	654
0.4-0.5	168
0.5-0.6	20
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC271385
0.7879	Intermediate Similarity	NPC76128
0.7846	Intermediate Similarity	NPC278329
0.7313	Intermediate Similarity	NPC5029
0.7231	Intermediate Similarity	NPC111536
0.6812	Remote Similarity	NPC30432
0.6571	Remote Similarity	NPC146837
0.6538	Remote Similarity	NPC46958
0.6479	Remote Similarity	NPC101116
0.6269	Remote Similarity	NPC483778
0.6216	Remote Similarity	NPC178281
0.5942	Remote Similarity	NPC605264
0.5902	Remote Similarity	NPC245584
0.5733	Remote Similarity	NPC212099
0.5625	Remote Similarity	NPC12308
0.5493	Remote Similarity	NPC199335
0.5429	Remote Similarity	NPC222455
0.5429	Remote Similarity	NPC106025
0.5357	Remote Similarity	NPC105591
0.5325	Remote Similarity	NPC199357
0.5278	Remote Similarity	NPC477240
0.527	Remote Similarity	NPC600107
0.5205	Remote Similarity	NPC190217
0.5195	Remote Similarity	NPC212290
0.5195	Remote Similarity	NPC604833
0.5147	Remote Similarity	NPC40377
0.5135	Remote Similarity	NPC610808
0.5077	Remote Similarity	NPC152722
0.5068	Remote Similarity	NPC475628
0.5067	Remote Similarity	NPC604892
0.5065	Remote Similarity	NPC606849

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC112504 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5008
0.1-0.2	4030
0.2-0.3	101
0.3-0.4	7
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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