NPASS Compound

Natural Product: NPC28398

Natural Product ID	NPC28398
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(8S,8'r)-4-Hydroxy-3',4'-Methylenedioxy-7-Ona-8,8'-Ignan
IUPAC Name	(2S,3R)-4-(1,3-benzodioxol-5-yl)-1-(4-hydroxyphenyl)-2,3-dimethylbutan-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL261195
PubChem CID	44450606
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 43 45 0 0 0 0 0 0 0 0999 V2000 0.8380 1.8014 -1.2688 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3603 0.6789 -0.3439 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0138 -0.5896 -0.8100 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4879 -0.4655 -0.7415 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2313 -0.0034 -1.7890 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6199 0.1101 -1.7133 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2631 -0.2505 -0.5581 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5253 -0.7217 0.5153 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1526 -0.8259 0.4189 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4593 -0.9991 1.5250 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7299 -1.1684 0.8861 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6182 -0.2501 -0.1851 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1282 0.6573 -0.4118 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5976 2.0395 0.0679 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7791 -0.3478 0.4081 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1124 -1.1050 1.1386 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2182 -0.4886 0.3915 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8682 -1.4259 1.1688 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2431 -1.5629 1.1505 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0191 -0.7707 0.3569 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4078 0.1707 -0.4281 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0295 0.3055 -0.4076 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3955 -0.9212 0.3508 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8895 2.0205 -1.0443 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6961 1.5095 -2.3355 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2067 2.7024 -1.1283 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6658 0.8742 0.6878 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6524 -1.5027 -0.3342 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7686 -0.6963 -1.9069 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7197 0.2788 -2.6968 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1658 0.4811 -2.5685 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5747 -1.1937 1.2563 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5427 -0.8452 1.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8087 -2.1946 0.5202 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4196 0.5807 -1.4967 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8852 2.6975 -0.7569 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4228 1.9430 0.8191 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7850 2.5653 0.6377 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3070 -2.0888 1.8237 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7027 -2.3238 1.7886 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0515 0.7868 -1.0494 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6179 1.0652 -1.0525 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0001 -0.5271 1.0484 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 2 13 1 0 13 14 1 0 13 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 20 23 1 0 9 4 1 0 22 17 1 0 12 7 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 1 3 28 1 0 3 29 1 0 5 30 1 0 6 31 1 0 9 32 1 0 11 33 1 0 11 34 1 0 13 35 1 6 14 36 1 0 14 37 1 0 14 38 1 0 18 39 1 0 19 40 1 0 21 41 1 0 22 42 1 0 23 43 1 0 M END

Standard InCHIKey	ADYNTRRRWKUCKH-OLZOCXBDSA-N
Standard InCHI	InChI=1S/C19H20O4/c1-12(9-14-3-8-17-18(10-14)23-11-22-17)13(2)19(21)15-4-6-16(20)7-5-15/h3-8,10,12-13,20H,9,11H2,1-2H3/t12-,13+/m1/s1
SMILES	C[C@H](Cc1ccc2c(c1)OCO2)[C@H](C)C(=O)c1ccc(cc1)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
NPO2754	Iryanthera lancifolia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10579855]
NPO2754	Iryanthera lancifolia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18242997]
NPO2754	Iryanthera lancifolia	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
MED	1
Ratio	1
Activity	2

Activity Type	# Activity
Cell line	4

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
NPT83	Cell line	MCF7	Homo sapiens	MED	=	10.0	uM	PMID[18242997]
NPT83	Cell line	MCF7	Homo sapiens	Ratio	=	4.51	n.a.	PMID[19813743]
NPT83	Cell line	MCF7	Homo sapiens	Activity	=	0.01	%	PMID[23327668]
NPT83	Cell line	MCF7	Homo sapiens	Activity	=	50.1	%	DOI[10.1271/bbb.56.1835]

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 NPC28398 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	22299
0.1-0.2	22980
0.2-0.3	4223
0.3-0.4	283
0.4-0.5	51
0.5-0.6	13
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
0.7872	Intermediate Similarity	NPC485482
0.7736	Intermediate Similarity	NPC46880
0.75	Intermediate Similarity	NPC249788
0.6304	Remote Similarity	NPC80241
0.6304	Remote Similarity	NPC301641
0.6304	Remote Similarity	NPC485483
0.6182	Remote Similarity	NPC474990
0.6	Remote Similarity	NPC274356
0.6	Remote Similarity	NPC101748
0.5926	Remote Similarity	NPC485480
0.58	Remote Similarity	NPC344161
0.541	Remote Similarity	NPC487677
0.541	Remote Similarity	NPC487675
0.5357	Remote Similarity	NPC104077
0.5357	Remote Similarity	NPC219671
0.5357	Remote Similarity	NPC147616
0.5294	Remote Similarity	NPC40352
0.5294	Remote Similarity	NPC213711
0.5238	Remote Similarity	NPC106739
0.5156	Remote Similarity	NPC471505
0.5077	Remote Similarity	NPC487679
0.5077	Remote Similarity	NPC487678

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC28398 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3695
0.1-0.2	5157
0.2-0.3	286
0.3-0.4	8
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