NPASS Compound

Natural Product: NPC545026

Natural Product ID	NPC545026
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-Hydroxy-6-methoxyflavone
IUPAC Name	5-hydroxy-6-methoxy-2-phenyl-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 32 34 0 0 0 0 0 0 0 0999 V2000 5.8440 0.4140 0.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8580 -0.2404 -0.6457 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5013 -0.0924 -0.4250 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0453 0.7322 0.5800 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6996 0.9085 0.8345 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7445 0.2522 0.0763 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5316 0.4273 0.3270 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4948 -0.1686 -0.3582 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8763 0.0939 0.0008 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9197 -0.4956 -0.6743 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2462 -0.2409 -0.3263 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5491 0.6100 0.7055 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5147 1.2061 1.3888 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1842 0.9478 1.0364 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0799 -0.9999 -1.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2286 -1.2310 -1.6890 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6151 -1.9845 -2.6063 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2009 -0.5794 -0.9371 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5435 -0.7414 -1.1741 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9328 -1.5840 -2.1986 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8331 0.4068 -0.3742 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9950 -0.0693 1.1167 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5872 1.4869 0.2634 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7824 1.2498 1.1788 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4137 1.5731 1.6418 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7705 -1.1793 -1.5002 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0584 -0.7071 -0.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5987 0.8004 0.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7309 1.8851 2.2112 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3632 1.4024 1.5564 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8307 -1.5066 -1.9548 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9240 -2.5759 -2.0344 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 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 8 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 19 3 1 0 18 6 1 0 14 9 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 5 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 13 29 1 0 14 30 1 0 15 31 1 0 20 32 1 0 M END

Standard InCHIKey	KQFFAKXFTDOCIR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O4/c1-19-13-8-7-12-15(16(13)18)11(17)9-14(20-12)10-5-3-2-4-6-10/h2-9,18H,1H3
SMILES	COC1=CC=C2OC(C3=CC=CC=C3)=CC(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	268.07	Volume:	273.692 ? Van der Waals volume.
Dense:	0.979	LogP:	3.321 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.062 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.396 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	59.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.775	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.025	Fsp³:	0.062
MCE-18:	16.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.323	Fluc inhibitor:	0.989 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.761 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.663 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.675	Promiscuous compounds:	0.496

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.819	MDCK Permeability:	-4.696
Pgp-inhibitor:	0.972	Pgp-substrate:	0.129
PAMPA:	0.116 ? 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):	0.005
20% Bioavailability (F20%):	0.053	30% Bioavailability (F30%):	0.42
50% Bioavailability (F50%):	0.868

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.331	MRP1:	0.848
Plasma Protein Binding (PPB):	98.833%	Volume Distribution (VD):	-0.507
Fu:	0.574% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.945
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.922
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.239	CYP1A2-substrate:	0.961
CYP2C19-inhibitor:	0.027	CYP2C19-substrate:	0.042
CYP2C9-inhibitor:	0.979	CYP2C9-substrate:	0.114
CYP2D6-inhibitor:	0.955	CYP2D6-substrate:	0.701
CYP3A4-inhibitor:	0.483	CYP3A4-substrate:	0.846
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	0.446
HLM stability:	0.591 ? 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):

2.773

Half-life (T1/2):

1.59

ADMET: Toxicity

hERG Blockers:	0.102	hERG Blockers (10um):	0.489
Human Hepatotoxicity (H-HT):	0.485	Drug-induced Liver Injury (DILI):	0.893
AMES Toxicity:	0.559	Rat Oral Acute Toxicity:	0.477
Maximum Recommended Daily Dose:	0.604	Skin Sensitization:	0.519
Carcinogencity:	0.774	Eye Corrosion:	0.271
Eye Irritation:	0.985	Respiratory Toxicity:	0.764
Drug-induced Neurotoxicity:	0.152	Ototoxicity:	0.1
Hematotoxicity:	0.189	Drug-induced Nephrotoxicity:	0.13
Genotoxicity:	0.73	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.199	Hek293 Cytotoxicity:	0.402
BCF:	1.219 ? 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:	4.104 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.885 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.609 ? 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
NPO22512	Primula sinensis	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21813	Primula pulverulenta	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53297	Primula acaulis	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21813	Primula pulverulenta	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21813	Primula pulverulenta	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22512	Primula sinensis	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21813	Primula pulverulenta	Species	Primulaceae	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

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

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 NPC545026 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	26895
0.1-0.2	19303
0.2-0.3	2831
0.3-0.4	568
0.4-0.5	187
0.5-0.6	56
0.6-0.7	10
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
0.7115	Intermediate Similarity	NPC293183
0.6981	Remote Similarity	NPC239128
0.6667	Remote Similarity	NPC275722
0.6538	Remote Similarity	NPC607644
0.6364	Remote Similarity	NPC127447
0.625	Remote Similarity	NPC18260
0.6182	Remote Similarity	NPC602963
0.6154	Remote Similarity	NPC197425
0.6071	Remote Similarity	NPC156222
0.6071	Remote Similarity	NPC187498
0.6038	Remote Similarity	NPC41721
0.5965	Remote Similarity	NPC145379
0.5932	Remote Similarity	NPC608539
0.5893	Remote Similarity	NPC131624
0.5862	Remote Similarity	NPC256283
0.5789	Remote Similarity	NPC241498
0.5789	Remote Similarity	NPC306821
0.5789	Remote Similarity	NPC194281
0.5789	Remote Similarity	NPC609062
0.569	Remote Similarity	NPC53181
0.569	Remote Similarity	NPC57030
0.569	Remote Similarity	NPC120163
0.5667	Remote Similarity	NPC160951
0.5593	Remote Similarity	NPC604312
0.5536	Remote Similarity	NPC284424
0.5517	Remote Similarity	NPC284552
0.5517	Remote Similarity	NPC482122
0.5517	Remote Similarity	NPC29353
0.5517	Remote Similarity	NPC609958
0.55	Remote Similarity	NPC69394
0.55	Remote Similarity	NPC83508
0.55	Remote Similarity	NPC255350
0.5455	Remote Similarity	NPC239312
0.5455	Remote Similarity	NPC78540
0.5439	Remote Similarity	NPC201395
0.5424	Remote Similarity	NPC100887
0.5424	Remote Similarity	NPC184136
0.5424	Remote Similarity	NPC231772
0.5424	Remote Similarity	NPC198826
0.5424	Remote Similarity	NPC276409
0.5424	Remote Similarity	NPC604085
0.5345	Remote Similarity	NPC75279
0.5345	Remote Similarity	NPC599976
0.5333	Remote Similarity	NPC25270
0.5333	Remote Similarity	NPC603662
0.5323	Remote Similarity	NPC47781
0.5263	Remote Similarity	NPC2771
0.5263	Remote Similarity	NPC278556
0.5263	Remote Similarity	NPC106461
0.5254	Remote Similarity	NPC274327
0.5254	Remote Similarity	NPC488084
0.5254	Remote Similarity	NPC483774
0.5246	Remote Similarity	NPC212678
0.5231	Remote Similarity	NPC602829
0.5167	Remote Similarity	NPC176775
0.5167	Remote Similarity	NPC22519
0.5167	Remote Similarity	NPC234133
0.5161	Remote Similarity	NPC283600
0.5161	Remote Similarity	NPC52005
0.5161	Remote Similarity	NPC223579
0.5094	Remote Similarity	NPC32298
0.5085	Remote Similarity	NPC601286
0.5085	Remote Similarity	NPC607196
0.5082	Remote Similarity	NPC78913
0.5082	Remote Similarity	NPC217186
0.5082	Remote Similarity	NPC162313
0.5075	Remote Similarity	NPC470402

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC545026 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4197
0.1-0.2	4735
0.2-0.3	208
0.3-0.4	7
0.4-0.5	2
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
0.55	Remote Similarity	NPD2801	Pre-clinical

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