NPASS Compound

Natural Product: NPC177298

Natural Product ID	NPC177298
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lethedocin
IUPAC Name	5-hydroxy-2-(3-hydroxy-4,5-dimethoxyphenyl)-7-methoxychromen-4-one
Synonyms	Lethedocin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL467609
PubChem CID	5496476
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002592] 7-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 41 43 0 0 0 0 0 0 0 0999 V2000 4.8610 2.8526 -0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4095 1.5580 -0.0581 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5242 0.4953 0.0802 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9648 -0.8033 0.2245 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1007 -1.8746 0.3634 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7354 -1.6697 0.3616 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8777 -2.7472 0.5011 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2876 -3.9249 0.6319 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5078 -2.4423 0.4877 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1074 -1.1472 0.3432 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3134 -0.7815 0.3235 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3037 -1.7271 0.4498 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6214 -1.3276 0.4245 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0020 -0.0114 0.2772 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0046 0.9372 0.1505 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6909 0.5463 0.1748 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3497 2.2715 0.0005 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3204 3.2392 -0.1290 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3145 0.4294 0.2470 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9509 0.4894 -1.0263 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6591 -2.2682 0.5510 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9774 -0.1836 0.2167 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2738 -0.3819 0.2189 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1409 0.6799 0.0810 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6083 -3.1706 0.5063 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6179 3.6487 -0.1506 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1936 2.9213 -1.0792 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1887 2.9985 0.6949 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0492 -0.9552 0.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1533 -3.2694 0.5949 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0737 -2.7831 0.5692 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8841 1.2911 0.0749 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6888 3.0310 -1.0238 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6244 3.2010 0.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7122 4.2589 -0.2210 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3837 -0.0990 -1.7882 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0410 1.5192 -1.3998 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9552 -0.0081 -0.9192 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6807 -2.7680 1.4417 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7857 1.6964 -0.0318 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5164 -3.7211 1.3303 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 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 14 19 1 0 19 20 1 0 13 21 1 0 10 22 1 0 22 23 1 0 23 24 2 0 5 25 1 0 24 3 1 0 23 6 1 0 16 11 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 9 30 1 0 12 31 1 0 16 32 1 0 18 33 1 0 18 34 1 0 18 35 1 0 20 36 1 0 20 37 1 0 20 38 1 0 21 39 1 0 24 40 1 0 25 41 1 0 M END

Standard InCHIKey	WFVABHHWJPWNJJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H16O7/c1-22-10-6-11(19)17-12(20)8-14(25-15(17)7-10)9-4-13(21)18(24-3)16(5-9)23-2/h4-8,19,21H,1-3H3
SMILES	COc1cc(c2c(=O)cc(c3cc(c(c(c3)OC)OC)O)oc2c1)O

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
NPO33004	lethedon tannaensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075750]
NPO33004	lethedon tannaensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8759170]

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
IC50	1

Activity Type	# Activity
Cell line	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
NPT91	Cell line	KB	Homo sapiens	IC50	=	16.4	ug.mL-1	DrugMatrix in vitro pharmacology data

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 NPC177298 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	31739
0.1-0.2	15081
0.2-0.3	2164
0.3-0.4	499
0.4-0.5	279
0.5-0.6	72
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7925	Intermediate Similarity	NPC33265
0.75	Intermediate Similarity	NPC195202
0.75	Intermediate Similarity	NPC223579
0.75	Intermediate Similarity	NPC206604
0.7273	Intermediate Similarity	NPC48479
0.7193	Intermediate Similarity	NPC606638
0.7143	Intermediate Similarity	NPC108406
0.7091	Intermediate Similarity	NPC127447
0.7091	Intermediate Similarity	NPC29353
0.7069	Intermediate Similarity	NPC137062
0.6964	Remote Similarity	NPC234133
0.6724	Remote Similarity	NPC328119
0.6167	Remote Similarity	NPC200740
0.6102	Remote Similarity	NPC76376
0.6066	Remote Similarity	NPC124784
0.6034	Remote Similarity	NPC75279
0.5902	Remote Similarity	NPC166753
0.5833	Remote Similarity	NPC87125
0.5833	Remote Similarity	NPC605755
0.5806	Remote Similarity	NPC160951
0.5806	Remote Similarity	NPC236769
0.5806	Remote Similarity	NPC609179
0.5738	Remote Similarity	NPC208197
0.5714	Remote Similarity	NPC252933
0.5667	Remote Similarity	NPC152042
0.5645	Remote Similarity	NPC39732
0.5645	Remote Similarity	NPC69394
0.5645	Remote Similarity	NPC270620
0.5645	Remote Similarity	NPC60972
0.5634	Remote Similarity	NPC600396
0.5574	Remote Similarity	NPC143799
0.5574	Remote Similarity	NPC62536
0.5574	Remote Similarity	NPC145379
0.5574	Remote Similarity	NPC276409
0.5574	Remote Similarity	NPC601901
0.5571	Remote Similarity	NPC248739
0.5556	Remote Similarity	NPC58382
0.5556	Remote Similarity	NPC474520
0.5526	Remote Similarity	NPC22832
0.5526	Remote Similarity	NPC243930
0.5493	Remote Similarity	NPC603508
0.5484	Remote Similarity	NPC25270
0.5469	Remote Similarity	NPC47781
0.5469	Remote Similarity	NPC78326
0.5455	Remote Similarity	NPC607707
0.5417	Remote Similarity	NPC158027
0.541	Remote Similarity	NPC103904
0.541	Remote Similarity	NPC262094
0.541	Remote Similarity	NPC239128
0.5405	Remote Similarity	NPC18699
0.5397	Remote Similarity	NPC246204
0.5397	Remote Similarity	NPC212678
0.5373	Remote Similarity	NPC99671
0.5373	Remote Similarity	NPC602829
0.5342	Remote Similarity	NPC159707
0.5342	Remote Similarity	NPC14606
0.5342	Remote Similarity	NPC194593
0.5323	Remote Similarity	NPC146679
0.5323	Remote Similarity	NPC188871
0.5323	Remote Similarity	NPC120163
0.5323	Remote Similarity	NPC483773
0.5312	Remote Similarity	NPC55619
0.5312	Remote Similarity	NPC283600
0.5312	Remote Similarity	NPC52005
0.5312	Remote Similarity	NPC162351
0.5312	Remote Similarity	NPC12200
0.527	Remote Similarity	NPC121649
0.5256	Remote Similarity	NPC311830
0.5238	Remote Similarity	NPC100916
0.52	Remote Similarity	NPC205026
0.52	Remote Similarity	NPC95090
0.52	Remote Similarity	NPC27408
0.5195	Remote Similarity	NPC55443
0.5156	Remote Similarity	NPC29841
0.5156	Remote Similarity	NPC200388
0.5156	Remote Similarity	NPC255350
0.5139	Remote Similarity	NPC604322
0.5135	Remote Similarity	NPC473043
0.5132	Remote Similarity	NPC181712
0.5132	Remote Similarity	NPC265624
0.5128	Remote Similarity	NPC284960
0.5079	Remote Similarity	NPC231772
0.5079	Remote Similarity	NPC57030
0.5079	Remote Similarity	NPC120464
0.5077	Remote Similarity	NPC93376
0.5075	Remote Similarity	NPC485299
0.5067	Remote Similarity	NPC261866
0.5067	Remote Similarity	NPC19709

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC177298 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5963
0.1-0.2	3117
0.2-0.3	60
0.3-0.4	6
0.4-0.5	2
0.5-0.6	1
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
0.5156	Remote Similarity	NPD2801	Pre-clinical

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