NPASS Compound

Natural Product: NPC218490

Natural Product ID	NPC218490
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4',6,7,Trihydroxyisoflavone
IUPAC Name	6,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one
Synonyms	4',6,7,-Trihydroxyisoflavone; 4',6,7-Trihydroxyisoflavone; 6,7,3'-Trihydroxyisoflavone; 6,7,4'-Trihydroxyisoflavone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL239156
PubChem CID	5284649
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002901] Isoflav-2-enes [CHEMONTID:0000494] 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 30 32 0 0 0 0 0 0 0 0999 V2000 -6.0696 0.2667 -0.7629 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7117 0.1694 -0.4576 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2006 0.6991 0.7055 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8764 0.6193 1.0311 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9948 -0.0240 0.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4905 -0.5664 -1.0255 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8353 -0.4665 -1.3212 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5966 -0.1521 0.4182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1593 -0.5315 1.6652 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1334 -0.6605 1.9441 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0882 -0.4443 1.0811 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7048 -0.0576 -0.1978 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3785 0.0874 -0.5272 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1019 0.4398 -1.7018 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6771 0.1882 -1.1646 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9931 0.0376 -0.8141 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3658 -0.3426 0.4436 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4347 -0.5935 1.4226 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7088 -0.4946 0.7952 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9848 0.2761 -1.7585 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5199 1.1669 -0.7852 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8912 1.2001 1.3860 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4659 1.0318 1.9413 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8225 -1.0689 -1.7169 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2142 -0.8966 -2.2528 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8360 -0.7402 2.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3711 0.4915 -2.1669 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6741 -0.8946 2.4257 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2539 0.2621 1.1955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8143 0.9979 -2.4245 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 2 0 5 6 1 0 6 7 2 0 5 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 12 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 16 20 1 0 7 2 1 0 13 8 1 0 18 11 1 0 1 21 1 0 3 22 1 0 4 23 1 0 6 24 1 0 7 25 1 0 9 26 1 0 15 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	GYLUFQJZYAJQDI-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-14-6-13(18)12(17)5-10(14)15(11)19/h1-7,16-18H
SMILES	Oc1ccc(cc1)c1coc2c(c1=O)cc(c(c2)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	270.05	Volume:	265.186 ? Van der Waals volume.
Dense:	1.018	LogP:	1.727 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.873 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.851 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	90.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.591	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.236	Fsp³:	0.0
MCE-18:	17.0 ? 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:	1
Colloidal aggregators:	0.741	Fluc inhibitor:	0.975 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.986 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.493 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.807	Promiscuous compounds:	0.823

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.955	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.001	Pgp-substrate:	0.048
PAMPA:	0.986 ? 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):	0.062
20% Bioavailability (F20%):	0.869	30% Bioavailability (F30%):	0.883
50% Bioavailability (F50%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.679
Plasma Protein Binding (PPB):	81.621%	Volume Distribution (VD):	-0.445
Fu:	19.202% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.637
OATP1B3 inhibitor:	0.617	BCRP inhibitor:	0.558
BSEP inhibitor:	0.452

ADMET: Metabolism

CYP1A2-inhibitor:	0.825	CYP1A2-substrate:	0.945
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.925
CYP2C9-inhibitor:	0.187	CYP2C9-substrate:	0.559
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.65
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.978
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.001 ? 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):

14.506

Half-life (T1/2):

1.537

ADMET: Toxicity

hERG Blockers:	0.16	hERG Blockers (10um):	0.7
Human Hepatotoxicity (H-HT):	0.447	Drug-induced Liver Injury (DILI):	0.615
AMES Toxicity:	0.576	Rat Oral Acute Toxicity:	0.542
Maximum Recommended Daily Dose:	0.785	Skin Sensitization:	0.882
Carcinogencity:	0.645	Eye Corrosion:	0.204
Eye Irritation:	0.992	Respiratory Toxicity:	0.583
Drug-induced Neurotoxicity:	0.13	Ototoxicity:	0.409
Hematotoxicity:	0.061	Drug-induced Nephrotoxicity:	0.059
Genotoxicity:	0.937	RPMI-8226 Immunitoxicity:	0.019
A549 Cytotoxicity:	0.618	Hek293 Cytotoxicity:	0.522
BCF:	1.152 ? 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:	4.004 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.58 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.274 ? 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
NPO32821	korean fermented soypaste	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[18722771]
NPO33272	aged korean fermented soybean paste	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[20022495]

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	13
FC	6
Ratio IC50	1
ED50	1
ID50	1

Activity Type	# Activity
Individual protein	13
Organism	2
Others	5
Cell line	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1119	Individual protein	Arachidonate 12-lipoxygenase	Homo sapiens	IC50	=	8700.0	nM	PMID[17850214]
NPT1139	Individual protein	Arachidonate 15-lipoxygenase, type II	Homo sapiens	IC50	>	100000.0	nM	PMID[21428375]
NPT1044	Individual protein	DNA topoisomerase II alpha	Homo sapiens	IC50	=	43.7	ug.mL-1	PMID[12873498]
NPT2739	Individual protein	Tyrosinase	Mus musculus	IC50	>	500000.0	nM	PMID[25692815]
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	FC	=	10.4	n.a.	PMID[19640714]
NPT106	Individual protein	Peroxisome proliferator-activated receptor delta	Homo sapiens	FC	=	6.5	n.a.	PMID[7853008]
NPT866	Individual protein	Peroxisome proliferator-activated receptor alpha	Homo sapiens	FC	=	1.8	n.a.	PMID[18490506]
NPT866	Individual protein	Peroxisome proliferator-activated receptor alpha	Homo sapiens	FC	=	4.0	n.a.	PubChem BioAssay data set
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	FC	=	2.3	n.a.	PMID[17958396]
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	FC	=	4.4	n.a.	PMID[19191551]
NPT792	Individual protein	Arachidonate 15-lipoxygenase	Homo sapiens	IC50	=	49000.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT967	Individual protein	Xanthine dehydrogenase	Homo sapiens	IC50	>	1000000.0	nM	PMID[24931277]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	IC50	>	50.0	ug.mL-1	PMID[11602674]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	500000.0	nM	PMID[20022495]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	IC50	>	50.0	ug.mL-1	PMID[22620987]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	32.6	nM	PMID[20100877]
NPT1	Others	Radical scavenging activity	n.a.	ED50	=	29.0	uM	PMID[19344175]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	6.0	n.a.	PMID[17850214]
NPT2	Others	Unspecified	n.a.	IC50	=	50.0	ug.mL-1	PMID[25050881]
NPT22410	Cell line	Melan-a	Mus musculus	IC50	>	500000.0	nM	PMID[20022495]
NPT2	Others	Unspecified	n.a.	ID50	>	500.0	ug ml-1	PMID[18172002]

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 NPC218490 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	36149
0.1-0.2	11765
0.2-0.3	1558
0.3-0.4	251
0.4-0.5	102
0.5-0.6	21
0.6-0.7	5
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
0.7234	Intermediate Similarity	NPC234560
0.7059	Intermediate Similarity	NPC10467
0.6296	Remote Similarity	NPC100971
0.6275	Remote Similarity	NPC242893
0.614	Remote Similarity	NPC603384
0.6078	Remote Similarity	NPC125449
0.6078	Remote Similarity	NPC39426
0.5926	Remote Similarity	NPC605229
0.5738	Remote Similarity	NPC607759
0.5714	Remote Similarity	NPC181124
0.5556	Remote Similarity	NPC235428
0.5536	Remote Similarity	NPC7013
0.5536	Remote Similarity	NPC269451
0.5472	Remote Similarity	NPC212767
0.5469	Remote Similarity	NPC610903
0.5439	Remote Similarity	NPC209560
0.5439	Remote Similarity	NPC490700
0.537	Remote Similarity	NPC324929
0.5283	Remote Similarity	NPC12367
0.5273	Remote Similarity	NPC38065
0.5172	Remote Similarity	NPC216769
0.5172	Remote Similarity	NPC162680
0.5172	Remote Similarity	NPC303644
0.5167	Remote Similarity	NPC139364
0.5088	Remote Similarity	NPC487215
0.5079	Remote Similarity	NPC608523
0.5077	Remote Similarity	NPC611071
0.5075	Remote Similarity	NPC600495

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC218490 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7120
0.1-0.2	2000
0.2-0.3	23
0.3-0.4	3
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6078	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