NPASS Compound

Natural Product: NPC474960

Natural Product ID	NPC474960
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-3-(8-Hydroxy-2,2-Dimethyl-3,4-Dihydrochromen-5-Yl)Chromen-4-One
IUPAC Name	5,7-dihydroxy-3-(8-hydroxy-2,2-dimethyl-3,4-dihydrochromen-5-yl)chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL490311
PubChem CID	11494111
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002901] Isoflav-2-enes [CHEMONTID:0000494] Isoflavones [CHEMONTID:0003580] 2'-prenylated isoflavones

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 44 47 0 0 0 0 0 0 0 0999 V2000 7.0020 -0.2877 -1.5268 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7420 -0.0662 -0.9774 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3957 1.2369 -0.6197 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1513 1.4700 -0.0746 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8029 2.7652 0.2826 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2708 0.4252 0.1098 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5861 -0.8776 -0.2351 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8413 -1.0879 -0.7809 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7357 -1.8574 -0.0522 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5363 -1.6782 0.4657 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1162 -0.4178 0.8463 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0052 0.6212 0.6574 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6909 1.7798 0.9780 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2179 -0.2211 1.4219 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4373 -0.3033 2.7808 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6803 -0.1231 3.3497 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7740 0.1528 2.5549 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5718 0.2396 1.1801 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3166 0.0558 0.6255 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0789 0.1449 -0.8326 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2811 -0.0328 -1.6786 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5815 -0.0692 -0.9737 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6055 0.5127 0.2937 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6557 0.5836 -1.8364 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0236 -1.5274 -0.8041 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0477 0.3434 3.0734 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8567 0.0716 -1.1137 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1145 2.0341 -0.7795 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8395 3.0647 1.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0981 -2.1053 -1.0546 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8743 -2.5317 0.5930 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4252 -0.5203 3.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8438 -0.1889 4.4141 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5942 1.1455 -1.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3104 -0.6067 -1.1476 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3090 0.8076 -2.4313 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2090 -0.9661 -2.3094 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1501 1.2078 -2.6164 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2535 -0.1723 -2.3905 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2841 1.2339 -1.2229 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3357 -1.9613 -1.7586 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9154 -1.4832 -0.1198 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2502 -2.1210 -0.2790 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3573 1.3103 3.2139 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 2 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 24 1 0 22 25 1 0 17 26 1 0 8 2 1 0 19 14 1 0 12 6 1 0 23 18 1 0 1 27 1 0 3 28 1 0 5 29 1 0 8 30 1 0 10 31 1 0 15 32 1 0 16 33 1 0 20 34 1 0 20 35 1 0 21 36 1 0 21 37 1 0 24 38 1 0 24 39 1 0 24 40 1 0 25 41 1 0 25 42 1 0 25 43 1 0 26 44 1 0 M END

Standard InCHIKey	CFGUDCVYJGCIHR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H18O6/c1-20(2)6-5-12-11(3-4-14(22)19(12)26-20)13-9-25-16-8-10(21)7-15(23)17(16)18(13)24/h3-4,7-9,21-23H,5-6H2,1-2H3
SMILES	Oc1cc(O)c2c(c1)occ(c2=O)c1ccc(c2c1CCC(O2)(C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.11	Volume:	351.9 ? Van der Waals volume.
Dense:	1.006	LogP:	2.594 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.201 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.888 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	23.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.616	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.943	Fsp³:	0.25
MCE-18:	56.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.633	Fluc inhibitor:	0.404 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.896 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.677 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.141	Promiscuous compounds:	0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.002	MDCK Permeability:	-4.752
Pgp-inhibitor:	0.045	Pgp-substrate:	0.034
PAMPA:	0.253 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.626	30% Bioavailability (F30%):	0.949
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.17	MRP1:	0.915
Plasma Protein Binding (PPB):	96.261%	Volume Distribution (VD):	0.032
Fu:	3.797% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.968
OATP1B3 inhibitor:	0.91	BCRP inhibitor:	0.942
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	0.423	CYP1A2-substrate:	0.979
CYP2C19-inhibitor:	0.025	CYP2C19-substrate:	0.92
CYP2C9-inhibitor:	0.876	CYP2C9-substrate:	0.817
CYP2D6-inhibitor:	0.056	CYP2D6-substrate:	0.753
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.985
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.975 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.903

Half-life (T1/2):

1.171

ADMET: Toxicity

hERG Blockers:	0.159	hERG Blockers (10um):	0.577
Human Hepatotoxicity (H-HT):	0.511	Drug-induced Liver Injury (DILI):	0.656
AMES Toxicity:	0.659	Rat Oral Acute Toxicity:	0.609
Maximum Recommended Daily Dose:	0.877	Skin Sensitization:	0.59
Carcinogencity:	0.804	Eye Corrosion:	0.004
Eye Irritation:	0.96	Respiratory Toxicity:	0.887
Drug-induced Neurotoxicity:	0.097	Ototoxicity:	0.251
Hematotoxicity:	0.091	Drug-induced Nephrotoxicity:	0.142
Genotoxicity:	0.88	RPMI-8226 Immunitoxicity:	0.097
A549 Cytotoxicity:	0.367	Hek293 Cytotoxicity:	0.724
BCF:	1.823 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.689 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.201 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.582 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[16441066]
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	root	n.a.	n.a.	PMID[16441066]
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11841	Psorothamnus arborescens	Species	Fabaceae	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
IC50	3

Activity Type	# Activity
Cell line	1
Organism	2

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
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	107000.0	nM	PMID[11858752]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	38400.0	nM	PMID[19555123]
NPT471	Organism	Trypanosoma brucei brucei	Trypanosoma brucei brucei	IC50	=	57900.0	nM	PMID[16124770]

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 NPC474960 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	22132
0.1-0.2	24564
0.2-0.3	2667
0.3-0.4	418
0.4-0.5	43
0.5-0.6	29
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	Natural Product ID
0.7083	Intermediate Similarity	NPC52889
0.5811	Remote Similarity	NPC85131
0.5802	Remote Similarity	NPC303174
0.5694	Remote Similarity	NPC483637
0.5641	Remote Similarity	NPC74178
0.5634	Remote Similarity	NPC309154
0.5584	Remote Similarity	NPC128774
0.5479	Remote Similarity	NPC254702
0.5479	Remote Similarity	NPC264550
0.5467	Remote Similarity	NPC200746
0.5443	Remote Similarity	NPC303197
0.5395	Remote Similarity	NPC232947
0.5333	Remote Similarity	NPC93552
0.5278	Remote Similarity	NPC19980
0.527	Remote Similarity	NPC142876
0.5256	Remote Similarity	NPC233918
0.5195	Remote Similarity	NPC213659
0.5195	Remote Similarity	NPC326109
0.5147	Remote Similarity	NPC39426
0.5139	Remote Similarity	NPC294409
0.5139	Remote Similarity	NPC490701
0.5135	Remote Similarity	NPC278323
0.5135	Remote Similarity	NPC194653
0.5125	Remote Similarity	NPC474052
0.5068	Remote Similarity	NPC239363
0.5065	Remote Similarity	NPC238279
0.5063	Remote Similarity	NPC268059
0.5062	Remote Similarity	NPC231763
0.5062	Remote Similarity	NPC482075
0.5062	Remote Similarity	NPC107838

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474960 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3551
0.1-0.2	5543
0.2-0.3	52
0.3-0.4	3
0.4-0.5	0
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
0.5147	Remote Similarity	NPD1510	Phase 2

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