NPASS Compound

Natural Product: NPC514513

Natural Product ID	NPC514513
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	10544-05-5
IUPAC Name	2-(3,4-dimethoxyphenyl)-7-hydroxy-5-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 40 42 0 0 0 0 0 0 0 0999 V2000 -6.1174 -0.8191 -1.8201 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5965 -0.2815 -0.6221 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2255 -0.2183 -0.4271 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3906 -0.6877 -1.4195 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0501 -0.6223 -1.2209 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4436 -0.1079 -0.0702 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0008 -0.0731 0.0657 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6236 0.4244 1.1802 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0089 0.4510 1.2957 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6092 0.8970 2.2966 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7549 -0.0484 0.2338 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1314 -0.0570 0.2719 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7402 0.4487 1.4038 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1476 0.4911 1.5548 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8460 -0.5607 -0.8010 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1483 -1.0461 -1.8922 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8568 -1.5568 -2.9805 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7755 -1.0315 -1.9169 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0645 -0.5302 -0.8492 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7387 -0.5316 -0.9073 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3213 0.3481 0.8911 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6911 0.3114 0.7540 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5740 0.7699 1.7209 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0868 1.3140 2.9315 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2095 -0.6176 -1.8182 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6398 -0.3638 -2.7042 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9129 -1.9265 -1.7750 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7626 -1.1038 -2.3454 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3555 -0.9830 -1.9814 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0699 0.8182 2.0191 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5416 -0.5060 1.8960 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3879 1.2856 2.3095 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6717 0.7443 0.6138 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9196 -0.5640 -0.7638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8669 -1.0013 -3.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2477 -1.4145 -2.7770 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9391 0.7629 1.8147 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3173 0.6599 3.4085 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6065 2.2985 2.6578 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9104 1.5646 3.6124 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 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 6 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 22 3 1 0 20 7 1 0 19 11 1 0 1 25 1 0 1 26 1 0 1 27 1 0 4 28 1 0 5 29 1 0 8 30 1 0 14 31 1 0 14 32 1 0 14 33 1 0 15 34 1 0 17 35 1 0 18 36 1 0 21 37 1 0 24 38 1 0 24 39 1 0 24 40 1 0 M END

Standard InCHIKey	NUJCNNARSCKFIJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H16O6/c1-21-13-5-4-10(6-15(13)22-2)14-9-12(20)18-16(23-3)7-11(19)8-17(18)24-14/h4-9,19H,1-3H3
SMILES	COC1=CC=C(C2=CC(=O)C3=C(OC)C=C(O)C=C3O2)C=C1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	328.09	Volume:	325.865 ? Van der Waals volume.
Dense:	1.007	LogP:	2.286 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.438 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.095 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	78.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.792	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.197	Fsp³:	0.167
MCE-18:	18.0 ? 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:	0.225	Fluc inhibitor:	0.857 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.936 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.7 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.34	Promiscuous compounds:	0.616

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.935	MDCK Permeability:	-4.719
Pgp-inhibitor:	0.265	Pgp-substrate:	0.32
PAMPA:	0.03 ? 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):	0.032
20% Bioavailability (F20%):	0.163	30% Bioavailability (F30%):	0.287
50% Bioavailability (F50%):	0.932

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.764
Plasma Protein Binding (PPB):	97.228%	Volume Distribution (VD):	-0.023
Fu:	2.285% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.957
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.981
BSEP inhibitor:	0.986

ADMET: Metabolism

CYP1A2-inhibitor:	0.983	CYP1A2-substrate:	0.674
CYP2C19-inhibitor:	0.297	CYP2C19-substrate:	0.321
CYP2C9-inhibitor:	0.689	CYP2C9-substrate:	0.121
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.02	CYP3A4-substrate:	0.442
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.679 ? 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):

6.819

Half-life (T1/2):

1.371

ADMET: Toxicity

hERG Blockers:	0.135	hERG Blockers (10um):	0.468
Human Hepatotoxicity (H-HT):	0.435	Drug-induced Liver Injury (DILI):	0.75
AMES Toxicity:	0.618	Rat Oral Acute Toxicity:	0.418
Maximum Recommended Daily Dose:	0.724	Skin Sensitization:	0.389
Carcinogencity:	0.838	Eye Corrosion:	0.704
Eye Irritation:	0.992	Respiratory Toxicity:	0.759
Drug-induced Neurotoxicity:	0.268	Ototoxicity:	0.09
Hematotoxicity:	0.242	Drug-induced Nephrotoxicity:	0.099
Genotoxicity:	0.866	RPMI-8226 Immunitoxicity:	0.075
A549 Cytotoxicity:	0.113	Hek293 Cytotoxicity:	0.554
BCF:	1.179 ? 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:	3.618 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.396 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.94 ? 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
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24354205]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	twig	n.a.	PMID[24354205]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34964904]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36529712]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2715	Murraya paniculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2715	Murraya paniculata	Species	Rutaceae	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 NPC514513 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	25015
0.1-0.2	21021
0.2-0.3	2897
0.3-0.4	667
0.4-0.5	203
0.5-0.6	39
0.6-0.7	9
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
0.75	Intermediate Similarity	NPC287101
0.7407	Intermediate Similarity	NPC47815
0.7407	Intermediate Similarity	NPC194281
0.7321	Intermediate Similarity	NPC50728
0.7143	Intermediate Similarity	NPC605047
0.6897	Remote Similarity	NPC12200
0.6897	Remote Similarity	NPC604422
0.6667	Remote Similarity	NPC70853
0.6441	Remote Similarity	NPC255350
0.6333	Remote Similarity	NPC195202
0.6316	Remote Similarity	NPC23955
0.6207	Remote Similarity	NPC215932
0.6167	Remote Similarity	NPC69394
0.6066	Remote Similarity	NPC283600
0.5932	Remote Similarity	NPC110639
0.5902	Remote Similarity	NPC183597
0.5862	Remote Similarity	NPC333230
0.5763	Remote Similarity	NPC85233
0.5738	Remote Similarity	NPC163780
0.5667	Remote Similarity	NPC77955
0.5667	Remote Similarity	NPC113089
0.5588	Remote Similarity	NPC213622
0.5574	Remote Similarity	NPC270465
0.5556	Remote Similarity	NPC256612
0.5556	Remote Similarity	NPC2476
0.5538	Remote Similarity	NPC605634
0.55	Remote Similarity	NPC230285
0.5469	Remote Similarity	NPC604021
0.5397	Remote Similarity	NPC470216
0.5397	Remote Similarity	NPC159103
0.5362	Remote Similarity	NPC183
0.5323	Remote Similarity	NPC231772
0.5323	Remote Similarity	NPC149127
0.5323	Remote Similarity	NPC62536
0.5323	Remote Similarity	NPC266597
0.5312	Remote Similarity	NPC261548
0.5312	Remote Similarity	NPC236223
0.5312	Remote Similarity	NPC603596
0.5167	Remote Similarity	NPC101294
0.5161	Remote Similarity	NPC205522
0.5161	Remote Similarity	NPC609062
0.5156	Remote Similarity	NPC166753
0.5085	Remote Similarity	NPC41721
0.5082	Remote Similarity	NPC29536
0.5079	Remote Similarity	NPC22519
0.5077	Remote Similarity	NPC52005
0.5077	Remote Similarity	NPC115323
0.5077	Remote Similarity	NPC606638
0.5077	Remote Similarity	NPC607642
0.5077	Remote Similarity	NPC608258
0.5075	Remote Similarity	NPC485299
0.5065	Remote Similarity	NPC222936
0.5065	Remote Similarity	NPC182045

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC514513 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4573
0.1-0.2	4470
0.2-0.3	97
0.3-0.4	7
0.4-0.5	1
0.5-0.6	1
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
0.6441	Remote Similarity	NPD2801	Pre-clinical
0.5672	Remote Similarity	NPD3817	Phase 3

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