NPASS Compound

Natural Product: NPC296917

Natural Product ID	NPC296917
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-Dihydroxy-2-(4-Methoxyphenyl)-6,8-Dimethyl-2,3-Dihydrochromen-4-One
IUPAC Name	5,7-dihydroxy-2-(4-methoxyphenyl)-6,8-dimethyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1224711
PubChem CID	602155
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002596] 4'-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 -5.8717 0.2010 -0.1564 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4025 -0.0001 -0.0592 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8836 -1.1821 0.4138 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5220 -1.3653 0.5026 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9886 -2.6589 1.0200 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6175 -0.3882 0.1276 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1540 0.7980 -0.3473 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2338 1.8401 -0.7478 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6607 2.8522 -1.3540 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2034 1.7580 -0.4677 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5617 0.6007 0.4306 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9940 0.3066 0.2365 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4388 -0.4094 -0.8375 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8037 -0.6846 -1.0143 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7090 -0.2206 -0.0823 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2674 0.5052 1.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8985 0.7681 1.1642 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0374 -0.5069 -0.2843 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0884 -0.1171 0.5561 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2505 -0.5365 0.2027 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5147 1.0030 -0.4447 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9722 2.2128 -0.9280 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7309 -2.2042 0.8073 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3845 -0.1032 0.7782 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2440 -0.3861 -1.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0547 1.2766 -0.3915 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9904 -2.5467 1.4807 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9882 -3.3684 0.1545 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7059 -3.0980 1.7676 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5930 2.6801 0.0230 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8197 1.6475 -1.4057 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3709 0.9190 1.4742 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7367 -0.7765 -1.5721 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1556 -1.2514 -1.8647 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0007 0.8511 1.7147 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6207 1.3347 2.0289 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4995 0.8825 0.2798 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8350 -0.1599 1.6240 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9193 -0.8613 0.3995 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9200 2.4725 -1.9165 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4631 -2.0842 1.5016 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 1 0 4 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 15 18 1 0 18 19 1 0 11 20 1 0 7 21 2 0 21 22 1 0 3 23 1 0 21 2 1 0 20 6 1 0 17 12 1 0 1 24 1 0 1 25 1 0 1 26 1 0 5 27 1 0 5 28 1 0 5 29 1 0 10 30 1 0 10 31 1 0 11 32 1 0 13 33 1 0 14 34 1 0 16 35 1 0 17 36 1 0 19 37 1 0 19 38 1 0 19 39 1 0 22 40 1 0 23 41 1 0 M END

Standard InCHIKey	DZTRDRPCROOSOG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H18O5/c1-9-16(20)10(2)18-15(17(9)21)13(19)8-14(23-18)11-4-6-12(22-3)7-5-11/h4-7,14,20-21H,8H2,1-3H3
SMILES	Cc1c(c(C)c2c(C(=O)CC(c3ccc(cc3)OC)O2)c1O)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
NPO14359	Pentarhizidium orientale	Species	Onocleaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[28984452]
NPO14359	Pentarhizidium orientale	Species	Onocleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO183	Rhododendron simsii	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO183	Rhododendron simsii	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14359	Pentarhizidium orientale	Species	Onocleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO183	Rhododendron simsii	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO183	Rhododendron simsii	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14359	Pentarhizidium orientale	Species	Onocleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO183	Rhododendron simsii	Species	Ericaceae	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
Activity	4
IC50	2

Activity Type	# Activity
Cell line	4
Others	1
Non-molecular	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
NPT116	Cell line	HL-60	Homo sapiens	Activity	=	8.52	%	PMID[20708932]
NPT547	Cell line	BGC-823	Homo sapiens	Activity	=	-28.89	%	PMID[20708932]
NPT181	Cell line	Bel-7402	Homo sapiens	Activity	=	15.15	%	PMID[20708932]
NPT91	Cell line	KB	Homo sapiens	Activity	=	-11.99	%	PMID[20708932]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[20708932]
NPT2	Others	Unspecified	n.a.	IC50	>	100000.0	nM	PMID[20708932]

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 NPC296917 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	24782
0.1-0.2	21344
0.2-0.3	3196
0.3-0.4	388
0.4-0.5	107
0.5-0.6	24
0.6-0.7	8
0.7-0.8	1
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	NPC170907
0.7872	Intermediate Similarity	NPC248372
0.7755	Intermediate Similarity	NPC480995
0.7755	Intermediate Similarity	NPC477503
0.7708	Intermediate Similarity	NPC167624
0.7708	Intermediate Similarity	NPC166482
0.717	Intermediate Similarity	NPC270789
0.7059	Intermediate Similarity	NPC192083
0.6667	Remote Similarity	NPC231134
0.6538	Remote Similarity	NPC110038
0.6415	Remote Similarity	NPC324134
0.6415	Remote Similarity	NPC485881
0.6415	Remote Similarity	NPC40833
0.6296	Remote Similarity	NPC2416
0.6226	Remote Similarity	NPC110776
0.6111	Remote Similarity	NPC480992
0.5926	Remote Similarity	NPC215885
0.5849	Remote Similarity	NPC6407
0.5849	Remote Similarity	NPC545184
0.5741	Remote Similarity	NPC20354
0.5741	Remote Similarity	NPC162869
0.566	Remote Similarity	NPC188243
0.566	Remote Similarity	NPC213322
0.566	Remote Similarity	NPC110228
0.5636	Remote Similarity	NPC274784
0.5636	Remote Similarity	NPC20709
0.5556	Remote Similarity	NPC603284
0.5536	Remote Similarity	NPC476153
0.5439	Remote Similarity	NPC469758
0.5439	Remote Similarity	NPC271590
0.541	Remote Similarity	NPC148757
0.5357	Remote Similarity	NPC194432
0.5357	Remote Similarity	NPC480993
0.52	Remote Similarity	NPC488495
0.5179	Remote Similarity	NPC312391
0.5179	Remote Similarity	NPC177354
0.5161	Remote Similarity	NPC149026
0.5088	Remote Similarity	NPC156057
0.5088	Remote Similarity	NPC324386
0.5079	Remote Similarity	NPC310130

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC296917 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3680
0.1-0.2	5315
0.2-0.3	146
0.3-0.4	4
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7059	Intermediate Similarity	NPD2393	Clinical (unspecified phase)

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