NPASS Compound

Natural Product: NPC295384

Natural Product ID	NPC295384
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4',5,7-Trihydroxy-6,8-Dimethylisoflavone
IUPAC Name	5,7-dihydroxy-3-(4-hydroxyphenyl)-6,8-dimethylchromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL512579
PubChem CID	637048
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 36 38 0 0 0 0 0 0 0 0999 V2000 6.8123 -1.0204 0.3783 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4499 -0.7096 0.2800 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9620 0.0230 -0.7823 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6168 0.3246 -0.8705 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7095 -0.0887 0.0893 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2238 -0.8196 1.1407 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5632 -1.1320 1.2487 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2894 0.2366 -0.0154 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8806 1.5104 -0.3555 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3842 1.8553 -0.4631 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3681 0.9951 -0.2505 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0278 -0.3144 0.0981 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3005 -0.6968 0.2165 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6044 -1.8680 0.5282 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0438 -1.2096 0.3195 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7198 -2.5063 0.6644 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3527 -0.8259 0.2010 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6912 0.4783 -0.1461 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6819 1.3954 -0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0009 2.7942 -0.7451 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0260 0.8535 -0.2627 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4914 -1.7666 0.4327 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4035 -0.3273 0.7943 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6459 0.3620 -1.5512 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2137 0.9065 -1.7096 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5452 -1.1525 1.8980 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9404 -1.7173 2.1013 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6567 2.2402 -0.5367 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2245 -3.0753 1.3204 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2210 2.8676 -1.8305 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8877 3.1805 -0.1997 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1077 3.4325 -0.5535 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3460 1.6845 0.2139 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0531 -2.7832 0.4642 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9805 -1.4980 1.3813 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2094 -1.6286 -0.3825 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 1 0 15 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 18 21 1 0 17 22 1 0 7 2 1 0 13 8 1 0 19 11 1 0 1 23 1 0 3 24 1 0 4 25 1 0 6 26 1 0 7 27 1 0 9 28 1 0 16 29 1 0 20 30 1 0 20 31 1 0 20 32 1 0 21 33 1 0 22 34 1 0 22 35 1 0 22 36 1 0 M END

Standard InCHIKey	VSEIMGCATUFLSE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O5/c1-8-14(19)9(2)17-13(15(8)20)16(21)12(7-22-17)10-3-5-11(18)6-4-10/h3-7,18-20H,1-2H3
SMILES	Oc1ccc(cc1)c1coc2c(c1=O)c(O)c(c(c2C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	298.08	Volume:	299.778 ? Van der Waals volume.
Dense:	0.994	LogP:	2.131 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.021 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.413 ? 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:	0.642	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.518	Fsp³:	0.118
MCE-18:	19.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.689	Fluc inhibitor:	0.922 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.88 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.531 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.439	Promiscuous compounds:	0.25

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.055	MDCK Permeability:	-4.756
Pgp-inhibitor:	0.051	Pgp-substrate:	0.042
PAMPA:	0.92 ? 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):	0.003
20% Bioavailability (F20%):	0.192	30% Bioavailability (F30%):	0.164
50% Bioavailability (F50%):	0.727

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.188	MRP1:	0.963
Plasma Protein Binding (PPB):	96.669%	Volume Distribution (VD):	-0.36
Fu:	3.66% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.948
OATP1B3 inhibitor:	0.437	BCRP inhibitor:	0.175
BSEP inhibitor:	0.879

ADMET: Metabolism

CYP1A2-inhibitor:	0.984	CYP1A2-substrate:	0.933
CYP2C19-inhibitor:	0.119	CYP2C19-substrate:	0.888
CYP2C9-inhibitor:	0.979	CYP2C9-substrate:	0.125
CYP2D6-inhibitor:	0.98	CYP2D6-substrate:	0.935
CYP3A4-inhibitor:	0.008	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.958
HLM stability:	0.052 ? 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):

5.43

Half-life (T1/2):

1.007

ADMET: Toxicity

hERG Blockers:	0.077	hERG Blockers (10um):	0.512
Human Hepatotoxicity (H-HT):	0.533	Drug-induced Liver Injury (DILI):	0.47
AMES Toxicity:	0.483	Rat Oral Acute Toxicity:	0.638
Maximum Recommended Daily Dose:	0.665	Skin Sensitization:	0.686
Carcinogencity:	0.577	Eye Corrosion:	0.054
Eye Irritation:	0.986	Respiratory Toxicity:	0.883
Drug-induced Neurotoxicity:	0.285	Ototoxicity:	0.254
Hematotoxicity:	0.149	Drug-induced Nephrotoxicity:	0.127
Genotoxicity:	0.9	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.32	Hek293 Cytotoxicity:	0.581
BCF:	1.176 ? 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:	4.13 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.77 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.442 ? 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
NPO32723	henriettella fascicularis	Species	Melastomataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12502307]

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	4

Activity Type	# Activity
Individual protein	2
Cell line	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT248	Individual protein	Estrogen receptor beta	Homo sapiens	IC50	=	880.0	nM	DrugMatrix in vitro pharmacology data
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	IC50	=	10200.0	nM	PMID[17524651]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2738	Cell line	Ishikawa	Homo sapiens	IC50	>	20000.0	nM	DrugMatrix in vitro pharmacology data
NPT2738	Cell line	Ishikawa	Homo sapiens	IC50	=	10500.0	nM	DrugMatrix in vitro pharmacology data

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 NPC295384 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	28942
0.1-0.2	18588
0.2-0.3	2006
0.3-0.4	229
0.4-0.5	68
0.5-0.6	19
0.6-0.7	2
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
0.6607	Remote Similarity	NPC483565
0.6066	Remote Similarity	NPC204985
0.5441	Remote Similarity	NPC117836
0.5441	Remote Similarity	NPC51887
0.5424	Remote Similarity	NPC131266
0.5424	Remote Similarity	NPC269451
0.5397	Remote Similarity	NPC144118
0.5373	Remote Similarity	NPC6511
0.5357	Remote Similarity	NPC39426
0.5345	Remote Similarity	NPC487222
0.5283	Remote Similarity	NPC250057
0.5231	Remote Similarity	NPC222298
0.5231	Remote Similarity	NPC604003
0.5217	Remote Similarity	NPC237635
0.5211	Remote Similarity	NPC327269
0.5156	Remote Similarity	NPC259166
0.5152	Remote Similarity	NPC24673
0.5082	Remote Similarity	NPC216769
0.5082	Remote Similarity	NPC303644
0.507	Remote Similarity	NPC31627
0.507	Remote Similarity	NPC201731

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC295384 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5509
0.1-0.2	3595
0.2-0.3	42
0.3-0.4	2
0.4-0.5	1
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
0.5357	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