NPASS Compound

Natural Product: NPC281207

Natural Product ID	NPC281207
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3,7-Dihydroxy-4'-Methoxyflavone
IUPAC Name	3,7-dihydroxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2017116
PubChem CID	12314892
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0001136] Flavonols

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 33 35 0 0 0 0 0 0 0 0999 V2000 5.8408 1.1468 -0.0744 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3068 -0.1437 0.1859 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9223 -0.2793 0.2141 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3606 -1.5064 0.4616 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9661 -1.6736 0.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1193 -0.6393 0.2882 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7189 0.6008 0.0380 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0758 0.7859 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3448 -0.7174 0.3048 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0335 0.4008 0.0799 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3217 0.4948 0.0617 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9679 1.7068 -0.1821 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3353 1.8341 -0.2069 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9560 3.0549 -0.4525 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1008 0.6956 0.0230 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4806 -0.5135 0.2662 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0957 -0.6226 0.2874 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4637 -1.8163 0.5275 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1142 -2.8485 0.7359 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0613 -1.8514 0.5338 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4359 -3.0802 0.7810 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9521 1.1224 -0.0076 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4246 1.9252 0.5726 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5358 1.3962 -1.1307 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0110 -2.3674 0.6347 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5926 -2.6604 0.6951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0758 1.4700 -0.1367 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5405 1.7396 -0.1925 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3764 2.5946 -0.3613 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6235 3.8432 0.1243 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1717 0.7560 0.0114 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0242 -1.4358 0.4524 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5357 -3.4117 1.7522 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 8 3 1 0 20 9 2 0 17 11 1 0 1 22 1 0 1 23 1 0 1 24 1 0 4 25 1 0 5 26 1 0 7 27 1 0 8 28 1 0 12 29 1 0 14 30 1 0 15 31 1 0 16 32 1 0 21 33 1 0 M END

Standard InCHIKey	IYFVCSURXCCUSJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O5/c1-20-11-5-2-9(3-6-11)16-15(19)14(18)12-7-4-10(17)8-13(12)21-16/h2-8,17,19H,1H3
SMILES	COc1ccc(cc1)c1oc2cc(O)ccc2c(=O)c1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.07	Volume:	282.482 ? Van der Waals volume.
Dense:	1.006	LogP:	2.348 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.362 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.03 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.756	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.061	Fsp³:	0.062
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:	0
Colloidal aggregators:	0.587	Fluc inhibitor:	0.996 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.976 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.747 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.662	Promiscuous compounds:	0.883

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.134	MDCK Permeability:	-4.805
Pgp-inhibitor:	0.713	Pgp-substrate:	0.295
PAMPA:	0.333 ? 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):	0.522
20% Bioavailability (F20%):	0.354	30% Bioavailability (F30%):	0.892
50% Bioavailability (F50%):	0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.655
Plasma Protein Binding (PPB):	97.579%	Volume Distribution (VD):	-0.633
Fu:	1.83% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.884
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.975
BSEP inhibitor:	0.913

ADMET: Metabolism

CYP1A2-inhibitor:	0.662	CYP1A2-substrate:	0.086
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.873
CYP2C9-inhibitor:	0.779	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.937	CYP2D6-substrate:	0.618
CYP3A4-inhibitor:	0.096	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.953 ? 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):

6.311

Half-life (T1/2):

1.141

ADMET: Toxicity

hERG Blockers:	0.148	hERG Blockers (10um):	0.487
Human Hepatotoxicity (H-HT):	0.418	Drug-induced Liver Injury (DILI):	0.883
AMES Toxicity:	0.657	Rat Oral Acute Toxicity:	0.418
Maximum Recommended Daily Dose:	0.688	Skin Sensitization:	0.396
Carcinogencity:	0.843	Eye Corrosion:	0.693
Eye Irritation:	0.995	Respiratory Toxicity:	0.759
Drug-induced Neurotoxicity:	0.148	Ototoxicity:	0.108
Hematotoxicity:	0.149	Drug-induced Nephrotoxicity:	0.079
Genotoxicity:	0.787	RPMI-8226 Immunitoxicity:	0.055
A549 Cytotoxicity:	0.171	Hek293 Cytotoxicity:	0.53
BCF:	1.206 ? 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:	3.928 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.721 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.332 ? 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
NPO33390	broussonetia kanzinoki	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22450131]

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
Inhibition	1
IC50	1

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1120	Individual protein	Pancreatic triacylglycerol lipase	Sus scrofa	Inhibition	=	21.8	%	PMID[10479316]
NPT1120	Individual protein	Pancreatic triacylglycerol lipase	Sus scrofa	IC50	>	100000.0	nM	DOI[10.6019/CHEMBL1201861]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC281207 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	25579
0.1-0.2	20155
0.2-0.3	3263
0.3-0.4	681
0.4-0.5	135
0.5-0.6	27
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8077	Intermediate Similarity	NPC55205
0.7358	Intermediate Similarity	NPC605146
0.7273	Intermediate Similarity	NPC602125
0.72	Intermediate Similarity	NPC299379
0.7037	Intermediate Similarity	NPC266597
0.6909	Remote Similarity	NPC269652
0.6863	Remote Similarity	NPC51443
0.6727	Remote Similarity	NPC241838
0.6415	Remote Similarity	NPC74881
0.625	Remote Similarity	NPC44079
0.6207	Remote Similarity	NPC602344
0.614	Remote Similarity	NPC276905
0.6102	Remote Similarity	NPC604422
0.6034	Remote Similarity	NPC49824
0.5833	Remote Similarity	NPC607642
0.5789	Remote Similarity	NPC136840
0.5763	Remote Similarity	NPC209560
0.5763	Remote Similarity	NPC490700
0.5625	Remote Similarity	NPC269906
0.5593	Remote Similarity	NPC201451
0.5593	Remote Similarity	NPC260895
0.5593	Remote Similarity	NPC143799
0.5574	Remote Similarity	NPC608664
0.55	Remote Similarity	NPC86485
0.541	Remote Similarity	NPC54394
0.541	Remote Similarity	NPC50728
0.541	Remote Similarity	NPC159103
0.5333	Remote Similarity	NPC270465
0.5323	Remote Similarity	NPC115323
0.5238	Remote Similarity	NPC12175
0.5179	Remote Similarity	NPC93730
0.5167	Remote Similarity	NPC152042
0.5161	Remote Similarity	NPC200740
0.5161	Remote Similarity	NPC166753
0.5156	Remote Similarity	NPC55162
0.5082	Remote Similarity	NPC59951
0.5082	Remote Similarity	NPC231772
0.5082	Remote Similarity	NPC87125
0.5082	Remote Similarity	NPC604085
0.5079	Remote Similarity	NPC261548
0.5077	Remote Similarity	NPC607815

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC281207 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4103
0.1-0.2	4871
0.2-0.3	163
0.3-0.4	9
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