NPASS Compound

Natural Product: NPC552203

Natural Product ID	NPC552203
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7678-84-4
IUPAC Name	3-(2,4-dimethoxyphenyl)-7-methoxy-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 39 41 0 0 0 0 0 0 0 0999 V2000 -6.5603 0.5143 -1.2527 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7146 -0.2850 -0.4804 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3580 -0.0581 -0.3314 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6855 0.9787 -0.9252 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3425 1.1346 -0.7281 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5872 0.2729 0.0684 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1556 0.4682 0.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3277 1.2507 1.3013 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5990 1.4551 1.5115 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5064 0.9172 0.7266 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8568 1.1552 0.9785 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8583 0.6212 0.1937 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1826 0.8971 0.4990 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2721 0.4118 -0.2243 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4617 -0.1687 -0.8649 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1269 -0.4187 -1.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1435 0.1231 -0.3396 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8008 -0.0916 -0.5602 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4130 -0.8061 -1.5163 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2805 -0.7642 0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5790 -1.6528 1.4611 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2255 -2.7298 2.0899 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6363 -0.9370 0.4697 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3073 1.5831 -1.2377 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6340 0.1933 -2.3102 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6062 0.4468 -0.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2817 1.6488 -1.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8289 1.9586 -1.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3937 1.7062 1.9634 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1361 1.7767 1.8133 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1684 1.0675 -0.1476 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0149 0.4212 -1.3237 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5749 -0.6045 0.0220 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2561 -0.5947 -1.4905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8345 -1.0512 -1.9832 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8759 -2.3427 2.9142 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8662 -3.3236 1.4289 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4551 -3.4165 2.5003 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1595 -1.7569 0.9412 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 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 6 20 1 0 20 21 1 0 21 22 1 0 20 23 2 0 23 3 1 0 18 7 1 0 17 10 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 5 28 1 0 8 29 1 0 11 30 1 0 14 31 1 0 14 32 1 0 14 33 1 0 15 34 1 0 16 35 1 0 22 36 1 0 22 37 1 0 22 38 1 0 23 39 1 0 M END

Standard InCHIKey	RQVCRACKWBNBEO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H16O5/c1-20-11-4-6-13(16(8-11)22-3)15-10-23-17-9-12(21-2)5-7-14(17)18(15)19/h4-10H,1-3H3
SMILES	COC1=CC=C(C2=COC3=CC(OC)=CC=C3C2=O)C(OC)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	312.1	Volume:	317.074 ? Van der Waals volume.
Dense:	0.984	LogP:	2.431 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.688 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.551 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	57.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.738	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.03	Fsp³:	0.167
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:	0	PAINS Alert:	0
Colloidal aggregators:	0.299	Fluc inhibitor:	0.989 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.842 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.374 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.404	Promiscuous compounds:	0.633

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.578	MDCK Permeability:	-4.572
Pgp-inhibitor:	0.931	Pgp-substrate:	0.014
PAMPA:	0.005 ? 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):	0.286
20% Bioavailability (F20%):	0.075	30% Bioavailability (F30%):	0.146
50% Bioavailability (F50%):	0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.667
Plasma Protein Binding (PPB):	83.888%	Volume Distribution (VD):	-0.052
Fu:	13.793% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.99
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.428
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.966
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.985
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.349
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.984
HLM stability:	0.919 ? 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):

7.393

Half-life (T1/2):

0.592

ADMET: Toxicity

hERG Blockers:	0.365	hERG Blockers (10um):	0.542
Human Hepatotoxicity (H-HT):	0.509	Drug-induced Liver Injury (DILI):	0.924
AMES Toxicity:	0.731	Rat Oral Acute Toxicity:	0.47
Maximum Recommended Daily Dose:	0.681	Skin Sensitization:	0.06
Carcinogencity:	0.901	Eye Corrosion:	0.042
Eye Irritation:	0.929	Respiratory Toxicity:	0.802
Drug-induced Neurotoxicity:	0.654	Ototoxicity:	0.306
Hematotoxicity:	0.436	Drug-induced Nephrotoxicity:	0.55
Genotoxicity:	0.457	RPMI-8226 Immunitoxicity:	0.147
A549 Cytotoxicity:	0.146	Hek293 Cytotoxicity:	0.384
BCF:	1.353 ? 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:	3.861 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.032 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.458 ? 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
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(00)98060-9]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	Oakham, MA, US	n.a.	PMID[16562853]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17250743]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4986	Eschscholzia californica	Species	Papaveraceae	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 NPC552203 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	32237
0.1-0.2	15443
0.2-0.3	1779
0.3-0.4	287
0.4-0.5	86
0.5-0.6	12
0.6-0.7	8
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
0.7692	Intermediate Similarity	NPC216314
0.7255	Intermediate Similarity	NPC182428
0.7018	Intermediate Similarity	NPC55162
0.7018	Intermediate Similarity	NPC153008
0.6607	Remote Similarity	NPC136095
0.6545	Remote Similarity	NPC185607
0.6333	Remote Similarity	NPC254741
0.6316	Remote Similarity	NPC181124
0.6212	Remote Similarity	NPC607700
0.6066	Remote Similarity	NPC478213
0.6	Remote Similarity	NPC278323
0.6	Remote Similarity	NPC602183
0.5781	Remote Similarity	NPC185401
0.5667	Remote Similarity	NPC471590
0.5614	Remote Similarity	NPC182842
0.5593	Remote Similarity	NPC479067
0.5439	Remote Similarity	NPC120924
0.5246	Remote Similarity	NPC186507
0.5167	Remote Similarity	NPC474264
0.5161	Remote Similarity	NPC279061
0.5085	Remote Similarity	NPC223354
0.5082	Remote Similarity	NPC603503
0.5079	Remote Similarity	NPC262623
0.5068	Remote Similarity	NPC478528

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC552203 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5076
0.1-0.2	3970
0.2-0.3	101
0.3-0.4	1
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
0.5593	Remote Similarity	NPD2796	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