NPASS Compound

Natural Product: NPC544837

Natural Product ID	NPC544837
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6-[6-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2,3-dihydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
IUPAC Name	6-[6-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2,3-dihydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)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 59 64 0 0 0 0 0 0 0 0999 V2000 2.4802 -1.9359 1.8964 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8900 -1.1963 0.9415 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6203 0.1558 0.9178 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0820 0.9411 -0.1411 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7989 2.3687 -0.1687 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8364 3.2678 -0.1355 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6517 4.6217 -0.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3475 5.0835 -0.2165 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1586 6.4578 -0.2391 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2685 4.2189 -0.2517 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0158 4.7428 -0.3104 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5074 2.8404 -0.2271 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3531 1.9659 -0.2662 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1814 1.1318 -1.3362 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0731 1.0764 -2.4146 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9224 0.2927 -1.3744 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8674 0.2570 -0.3747 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9064 -0.5532 -0.4415 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8277 -0.6202 0.4846 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9639 -1.5559 0.3369 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9582 -1.6700 1.2730 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9942 -2.5536 1.0940 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0694 -3.3583 -0.0367 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1178 -4.2491 -0.2125 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0639 -3.2430 -0.9836 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0404 -2.3596 -0.7911 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6858 0.2052 1.5745 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6114 1.0755 1.6924 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5282 1.7970 2.6906 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6759 1.1121 0.7047 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5696 1.9554 0.7465 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4432 2.7811 1.8542 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7635 0.3309 -1.0765 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0413 -0.9504 -1.0915 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7697 -1.5386 -2.1138 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0652 -2.8870 -2.1347 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8016 -3.4620 -3.1745 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6333 -3.7079 -1.1136 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9067 -3.1401 -0.0872 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4634 -3.9487 0.9487 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6136 -1.7787 -0.0748 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0553 0.6261 1.7055 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8674 2.8893 -0.0888 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5124 5.2714 -0.1289 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1959 6.9456 -1.1475 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8070 4.1342 -0.5174 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8116 1.4446 -3.3345 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0437 -0.3627 -2.2306 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9411 -1.0716 2.1571 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8035 -2.6763 1.8109 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0381 -3.9055 -0.3716 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1521 -3.8886 -1.8595 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2706 -2.2738 -1.5196 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4100 0.1997 2.3739 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0297 2.3468 2.6882 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1303 -0.9373 -2.9370 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8196 -3.4395 -3.0377 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8653 -4.7706 -1.1284 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1919 -4.5027 1.4191 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 8 10 1 0 10 11 1 0 10 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 2 0 19 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 2 0 31 32 1 0 4 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 36 38 2 0 38 39 1 0 39 40 1 0 39 41 2 0 41 2 1 0 12 5 1 0 31 13 1 0 41 34 1 0 30 17 1 0 26 20 1 0 3 42 1 0 6 43 1 0 7 44 1 0 9 45 1 0 11 46 1 0 15 47 1 0 16 48 1 0 21 49 1 0 22 50 1 0 24 51 1 0 25 52 1 0 26 53 1 0 27 54 1 0 32 55 1 0 35 56 1 0 37 57 1 0 38 58 1 0 40 59 1 0 M END

Standard InCHIKey	BFEIVQIVRHQFCQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H18O11/c31-13-3-1-12(2-4-13)21-9-19(36)27-24(40-21)11-20(37)28(30(27)39)25-15(5-6-16(33)29(25)38)22-10-18(35)26-17(34)7-14(32)8-23(26)41-22/h1-11,31-34,37-39H
SMILES	O=C1C=C(C2=CC=C(O)C(O)=C2C2=C(O)C=C3OC(C4=CC=C(O)C=C4)=CC(=O)C3=C2O)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.08	Volume:	530.606 ? Van der Waals volume.
Dense:	1.044	LogP:	3.502 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.361 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.976 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	202.03 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.148	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.135	Fsp³:	0.0
MCE-18:	37.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.993	Fluc inhibitor:	0.68 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.609 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.924 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.651	Promiscuous compounds:	0.942

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.892	MDCK Permeability:	-4.863
Pgp-inhibitor:	0.0	Pgp-substrate:	0.173
PAMPA:	0.923 ? 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):	0.0
20% Bioavailability (F20%):	0.293	30% Bioavailability (F30%):	0.935
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.964
Plasma Protein Binding (PPB):	96.242%	Volume Distribution (VD):	-0.522
Fu:	3.252% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.948
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.773
BSEP inhibitor:	0.548

ADMET: Metabolism

CYP1A2-inhibitor:	0.197	CYP1A2-substrate:	0.035
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.176	CYP2C9-substrate:	0.057
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.165
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.795 ? 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):

2.651

Half-life (T1/2):

2.181

ADMET: Toxicity

hERG Blockers:	0.046	hERG Blockers (10um):	0.519
Human Hepatotoxicity (H-HT):	0.374	Drug-induced Liver Injury (DILI):	0.904
AMES Toxicity:	0.701	Rat Oral Acute Toxicity:	0.679
Maximum Recommended Daily Dose:	0.991	Skin Sensitization:	0.862
Carcinogencity:	0.714	Eye Corrosion:	0.003
Eye Irritation:	0.998	Respiratory Toxicity:	0.9
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.045
Hematotoxicity:	0.01	Drug-induced Nephrotoxicity:	0.005
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.89	Hek293 Cytotoxicity:	0.986
BCF:	1.102 ? 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:	4.19 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.671 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.353 ? 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
NPO2582	Plagiomnium undulatum	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2582	Plagiomnium undulatum	Species	Mniaceae	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 NPC544837 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	39317
0.1-0.2	8792
0.2-0.3	1171
0.3-0.4	471
0.4-0.5	78
0.5-0.6	21
0.6-0.7	6
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
0.7121	Intermediate Similarity	NPC111112
0.678	Remote Similarity	NPC50898
0.6667	Remote Similarity	NPC67322
0.6479	Remote Similarity	NPC603692
0.6351	Remote Similarity	NPC72425
0.6338	Remote Similarity	NPC254351
0.6032	Remote Similarity	NPC279121
0.5915	Remote Similarity	NPC138299
0.5733	Remote Similarity	NPC259757
0.5714	Remote Similarity	NPC78540
0.5606	Remote Similarity	NPC610974
0.5584	Remote Similarity	NPC600972
0.5538	Remote Similarity	NPC274121
0.5441	Remote Similarity	NPC231772
0.5405	Remote Similarity	NPC291746
0.5405	Remote Similarity	NPC288840
0.5395	Remote Similarity	NPC610480
0.5385	Remote Similarity	NPC222713
0.5385	Remote Similarity	NPC175013
0.5316	Remote Similarity	NPC290830
0.5316	Remote Similarity	NPC71061
0.5263	Remote Similarity	NPC34089
0.5263	Remote Similarity	NPC196179
0.5224	Remote Similarity	NPC213216
0.5152	Remote Similarity	NPC130230
0.5139	Remote Similarity	NPC183950
0.5125	Remote Similarity	NPC303485
0.5122	Remote Similarity	NPC205026

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC544837 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7938
0.1-0.2	1178
0.2-0.3	29
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
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
0.6032	Remote Similarity	NPD1511	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