NPASS Compound

Natural Product: NPC178854

Natural Product ID	NPC178854
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	8-O-Methylretusin
IUPAC Name	2-(3,4-dimethoxyphenyl)-5-hydroxy-3,7,8-trimethoxychromen-4-one
Synonyms	8-O-Methylretusin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479326
PubChem CID	10200272
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002593] 8-O-methylated flavonoids

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 48 50 0 0 0 0 0 0 0 0999 V2000 0.0836 3.3777 -5.8433 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3037 3.5185 -4.5027 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1784 2.5014 -3.5884 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3486 1.2870 -3.9841 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4682 0.2794 -3.0507 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1018 0.3952 -1.7478 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4291 1.6476 -1.4008 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5772 2.6865 -2.2695 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0961 3.9337 -1.9606 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5327 4.1764 -0.6114 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2758 -0.6014 -0.6954 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0982 -1.6674 -0.8264 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2434 -2.6146 0.2175 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0059 -3.5992 0.0870 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5091 -2.3889 1.3580 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5914 -3.2722 2.4330 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1478 -3.0270 3.5581 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9701 -1.9089 3.6244 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0598 -1.0289 2.5683 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2989 -1.2956 1.4283 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4158 -0.4298 0.4414 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8732 0.1020 2.6060 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2690 1.2938 3.0890 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7097 -1.7005 4.8022 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5796 -2.5861 5.8720 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4294 -4.3552 2.2912 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8473 -1.9257 -1.9344 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1710 -1.4268 -2.0141 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0246 2.7974 -5.8740 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2269 4.3861 -6.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7140 2.8989 -6.4620 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6786 1.0512 -4.9873 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8554 -0.6900 -3.4003 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7383 1.7836 -0.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6227 5.2601 -0.4485 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5387 3.6701 -0.5040 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8153 3.7568 0.1231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1064 -3.7005 4.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8857 1.8673 3.7807 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2980 1.1037 3.6115 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9927 1.9425 2.2075 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2255 -2.2648 6.7339 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8629 -3.6045 5.5163 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5400 -2.5867 6.2972 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1446 -5.2221 1.8529 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7693 -1.9812 -2.7783 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7357 -1.5178 -1.0647 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1727 -0.3216 -2.2537 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 19 22 1 0 22 23 1 0 18 24 1 0 24 25 1 0 16 26 1 0 12 27 1 0 27 28 1 0 8 3 1 0 21 11 1 0 20 15 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 5 33 1 0 7 34 1 0 10 35 1 0 10 36 1 0 10 37 1 0 17 38 1 0 23 39 1 0 23 40 1 0 23 41 1 0 25 42 1 0 25 43 1 0 25 44 1 0 26 45 1 0 28 46 1 0 28 47 1 0 28 48 1 0 M END

Standard InCHIKey	NPMMYTVKEWLZKD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H20O8/c1-23-12-7-6-10(8-13(12)24-2)17-20(27-5)16(22)15-11(21)9-14(25-3)18(26-4)19(15)28-17/h6-9,21H,1-5H3
SMILES	COc1ccc(cc1OC)c1c(c(=O)c2c(cc(c(c2o1)OC)OC)O)OC

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO11253	Knema glomerata	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8201311]
NPO11253	Knema glomerata	Species	Myristicaceae	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

Activity Type	# Activity
T/C	1
ED50	3

Activity Type	# Activity
Cell line	3
Organism	1

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
NPT81	Cell line	A549	Homo sapiens	ED50	=	27.15	ug ml-1	PMID[18547117]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	21.3	ug ml-1	PMID[22652254]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	26.34	ug ml-1	PubChem BioAssay data set
NPT141	Organism	Agrobacterium tumefaciens	Agrobacterium tumefaciens	T/C	=	52.0	%	PMID[8201311]

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
-	Artemia	LC50	=	56.53	ug.mL-1	DrugMatrix in vitro pharmacology data

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 NPC178854 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	29476
0.1-0.2	17394
0.2-0.3	2361
0.3-0.4	453
0.4-0.5	121
0.5-0.6	34
0.6-0.7	5
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8364	Intermediate Similarity	NPC603082
0.8077	Intermediate Similarity	NPC32557
0.7636	Intermediate Similarity	NPC603112
0.7547	Intermediate Similarity	NPC189960
0.75	Intermediate Similarity	NPC152166
0.7407	Intermediate Similarity	NPC605144
0.7321	Intermediate Similarity	NPC7846
0.7273	Intermediate Similarity	NPC607913
0.7018	Intermediate Similarity	NPC236769
0.7018	Intermediate Similarity	NPC605494
0.6441	Remote Similarity	NPC603596
0.6271	Remote Similarity	NPC176300
0.6271	Remote Similarity	NPC115798
0.625	Remote Similarity	NPC201547
0.6102	Remote Similarity	NPC86485
0.5938	Remote Similarity	NPC99671
0.5667	Remote Similarity	NPC301123
0.5667	Remote Similarity	NPC143828
0.5593	Remote Similarity	NPC259058
0.55	Remote Similarity	NPC306821
0.55	Remote Similarity	NPC262094
0.5484	Remote Similarity	NPC253634
0.5484	Remote Similarity	NPC238405
0.5484	Remote Similarity	NPC166753
0.541	Remote Similarity	NPC76376
0.5397	Remote Similarity	NPC224137
0.5397	Remote Similarity	NPC235215
0.5397	Remote Similarity	NPC195202
0.5397	Remote Similarity	NPC4481
0.5397	Remote Similarity	NPC2476
0.5333	Remote Similarity	NPC245546
0.5333	Remote Similarity	NPC7973
0.5312	Remote Similarity	NPC19687
0.5303	Remote Similarity	NPC76482
0.5246	Remote Similarity	NPC299923
0.5246	Remote Similarity	NPC310259
0.5246	Remote Similarity	NPC292107
0.5238	Remote Similarity	NPC257914
0.5238	Remote Similarity	NPC270620
0.5238	Remote Similarity	NPC265511
0.5211	Remote Similarity	NPC280493
0.5161	Remote Similarity	NPC105242
0.5161	Remote Similarity	NPC176665
0.5161	Remote Similarity	NPC606763
0.5156	Remote Similarity	NPC206604
0.5079	Remote Similarity	NPC22472
0.5079	Remote Similarity	NPC134677
0.5077	Remote Similarity	NPC78326
0.5075	Remote Similarity	NPC259411

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC178854 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5318
0.1-0.2	3763
0.2-0.3	63
0.3-0.4	5
0.4-0.5	1
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