NPASS Compound

Natural Product: NPC218092

Natural Product ID	NPC218092
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(5S,5Ar,8Ar)-5-(1,3-Benzodioxol-5-Yl)-5A,8,8A,9-Tetrahydro-5H-[2]Benzofuro[5,6-F][1,3]Benzodioxol-6-One
IUPAC Name	(5S,5aR,8aR)-5-(1,3-benzodioxol-5-yl)-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1976899
PubChem CID	386603
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones

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 42 47 0 0 0 0 0 0 0 0999 V2000 -1.9502 0.1803 1.0359 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9743 1.0232 1.4083 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4302 1.9720 0.4869 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8212 2.0057 -0.7487 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7951 1.1458 -1.0928 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3386 0.2014 -0.1806 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2515 -0.6996 -0.5640 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1083 -0.1402 -0.2291 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3099 1.2248 -0.2881 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5382 1.7916 0.0093 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5633 0.9461 0.3692 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3802 -0.4112 0.4327 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1526 -0.9676 0.1347 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0262 -2.4521 0.2250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7533 -2.9577 -0.3428 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2295 -4.2181 0.3011 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1614 -4.1395 -0.0478 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5340 -2.8079 -0.1707 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6835 -2.4129 -0.4844 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3568 -2.0033 0.1290 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6929 1.7063 0.6224 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4010 3.0450 0.3118 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0091 3.1062 0.0303 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4725 3.0383 -1.4544 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7547 3.2173 -0.8301 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4018 2.9451 0.5124 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6057 -0.5515 1.7603 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4335 0.9736 2.3856 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3374 1.2031 -2.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2333 -0.8533 -1.6624 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5144 1.8860 -0.5678 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2137 -1.0663 0.7226 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8853 -2.8933 -0.3317 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1204 -2.7238 1.2874 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7469 -3.0615 -1.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2857 -4.0750 1.3926 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7010 -5.1280 -0.0722 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1786 -1.9029 1.2287 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9829 3.3538 -0.5837 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6494 3.6872 1.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0516 4.2868 -0.8868 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4982 2.5260 -1.2338 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 11 21 1 0 21 22 1 0 22 23 1 0 4 24 1 0 24 25 1 0 25 26 1 0 6 1 1 0 20 7 1 0 26 3 1 0 13 8 1 0 20 15 1 0 23 10 1 0 1 27 1 0 2 28 1 0 5 29 1 0 7 30 1 6 9 31 1 0 12 32 1 0 14 33 1 0 14 34 1 0 15 35 1 6 16 36 1 0 16 37 1 0 20 38 1 1 22 39 1 0 22 40 1 0 25 41 1 0 25 42 1 0 M END

Standard InCHIKey	SCTKDFCQZSBHEE-NXXSPTCGSA-N
Standard InCHI	InChI=1S/C20H16O6/c21-20-19-12(7-22-20)3-11-5-16-17(26-9-25-16)6-13(11)18(19)10-1-2-14-15(4-10)24-8-23-14/h1-2,4-6,12,18-19H,3,7-9H2/t12-,18-,19-/m0/s1
SMILES	c1cc2c(cc1[C@H]1c3cc4c(cc3C[C@H]3COC(=O)[C@H]13)OCO4)OCO2

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
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1040	Ficus conraui	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO103	Stereocaulon salazinum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO617	Vicia balansae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1040	Ficus conraui	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO617	Vicia balansae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9031	Euonymus europaeus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO103	Stereocaulon salazinum	Species	Stereocaulaceae	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
GI50	44

Activity Type	# Activity
Cell line	44

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
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	21928.05	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	12022.64	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	15595.53	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	10616.96	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	16032.45	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	11994.99	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	4111.5	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	24660.39	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	9332.54	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	22698.65	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	24043.63	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	13867.56	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	18238.96	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	10990.06	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	24210.29	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	13273.94	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	24717.24	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	24099.05	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	25003.45	nM	PubChem BioAssay data set

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 NPC218092 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	28652
0.1-0.2	19951
0.2-0.3	994
0.3-0.4	179
0.4-0.5	54
0.5-0.6	12
0.6-0.7	3
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC246474
1.0	High Similarity	NPC162851
0.8	Intermediate Similarity	NPC80230
0.8	Intermediate Similarity	NPC104024
0.8	Intermediate Similarity	NPC101755
0.8	Intermediate Similarity	NPC304687
0.8	Intermediate Similarity	NPC65574
0.7857	Intermediate Similarity	NPC262455
0.7857	Intermediate Similarity	NPC177476
0.7167	Intermediate Similarity	NPC30009
0.7167	Intermediate Similarity	NPC103197
0.6071	Remote Similarity	NPC177167
0.6032	Remote Similarity	NPC149505
0.6032	Remote Similarity	NPC480477
0.5789	Remote Similarity	NPC115624
0.5588	Remote Similarity	NPC288149
0.5588	Remote Similarity	NPC115281
0.5588	Remote Similarity	NPC470637
0.5517	Remote Similarity	NPC110958
0.5517	Remote Similarity	NPC19890
0.55	Remote Similarity	NPC17348
0.5286	Remote Similarity	NPC163527
0.5161	Remote Similarity	NPC205915
0.5088	Remote Similarity	NPC476748
0.5077	Remote Similarity	NPC239890
0.5077	Remote Similarity	NPC209411

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC218092 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4980
0.1-0.2	4075
0.2-0.3	79
0.3-0.4	12
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