NPASS Compound

Natural Product: NPC543836

Natural Product ID	NPC543836
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3,5,7-trihydroxy-2-[4-hydroxy-3-[(3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyphenyl]chromen-4-one
IUPAC Name	3,5,7-trihydroxy-2-[4-hydroxy-3-[(3~{R},4~{S},5~{R})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-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 49 52 0 0 0 0 0 0 0 0999 V2000 5.7412 2.6105 1.2867 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8434 1.7771 1.0267 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4902 2.1397 0.9611 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2085 3.4759 1.2017 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4934 1.2603 0.6816 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0665 1.5846 0.6008 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5111 2.8153 0.7918 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8619 3.0242 0.6933 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7150 1.9714 0.3938 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0932 2.2663 0.3121 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1952 0.7183 0.1945 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9531 -0.3563 -0.0996 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2882 -0.5269 -0.2708 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8123 -1.5006 0.6466 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1889 -1.2939 0.6457 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8484 -1.6046 -0.6578 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.1522 -1.1046 -0.6050 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1133 -0.9824 -1.8367 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5149 -1.6920 -2.9679 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6239 -1.1687 -1.6386 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9309 -0.4353 -2.5934 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2076 0.5590 0.3061 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8757 0.0038 0.4674 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1217 -0.3838 0.5170 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4416 -1.7279 0.2787 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7257 -2.2076 0.3136 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9900 -3.5661 0.0668 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7260 -1.3130 0.5965 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4543 -0.0002 0.8334 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4631 0.9381 1.1260 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1619 0.4747 0.7967 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4372 3.8373 2.1267 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1354 3.6572 1.0254 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2851 4.0083 0.8482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3446 3.1646 -0.0773 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9307 0.3612 -0.1578 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6178 -1.9694 1.4130 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4350 -0.2268 0.9080 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8629 -2.6979 -0.8077 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1953 -0.2434 -0.1169 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3373 0.0914 -1.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6205 -2.6467 -2.6772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3327 -2.2177 -1.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9750 -0.9455 -3.4384 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5814 -0.4650 0.1381 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6139 -2.4159 0.0552 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4286 -3.8254 -0.8072 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7570 -1.6681 0.6306 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7527 1.5462 0.3503 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 3 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 11 22 2 0 5 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 26 28 2 0 28 29 1 0 29 30 1 0 29 31 2 0 31 2 1 0 22 6 1 0 31 24 1 0 20 13 1 0 4 32 1 0 7 33 1 0 8 34 1 0 10 35 1 0 13 36 1 0 15 37 1 0 15 38 1 0 16 39 1 6 17 40 1 0 18 41 1 6 19 42 1 0 20 43 1 1 21 44 1 0 22 45 1 0 25 46 1 0 27 47 1 0 28 48 1 0 30 49 1 0 M END

Standard InCHIKey	OIIVLLGYOWZKFZ-ANWMQUEKSA-N
Standard InCHI	InChI=1S/C20H18O11/c21-8-4-10(23)14-13(5-8)30-19(17(27)16(14)26)7-1-2-9(22)12(3-7)31-20-18(28)15(25)11(24)6-29-20/h1-5,11,15,18,20-25,27-28H,6H2/t11-,15+,18-,20?/m1/s1
SMILES	O=C1C(O)=C(C2=CC=C(O)C(OC3OC[C@@H](O)[C@H](O)[C@H]3O)=C2)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.08	Volume:	395.851 ? Van der Waals volume.
Dense:	1.097	LogP:	0.77 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.175 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.768 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	190.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.296	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.951	Fsp³:	0.25
MCE-18:	88.4 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.622	Fluc inhibitor:	0.281 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.891 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.805 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.104	Promiscuous compounds:	0.867

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.249	MDCK Permeability:	-5.01
Pgp-inhibitor:	0.001	Pgp-substrate:	0.41
PAMPA:	0.992 ? 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%):	0.047	30% Bioavailability (F30%):	0.896
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.198
Plasma Protein Binding (PPB):	88.651%	Volume Distribution (VD):	-0.372
Fu:	8.421% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.994
BSEP inhibitor:	0.207

ADMET: Metabolism

CYP1A2-inhibitor:	0.293	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.068
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.989 ? 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):

2.765

Half-life (T1/2):

3.594

ADMET: Toxicity

hERG Blockers:	0.023	hERG Blockers (10um):	0.266
Human Hepatotoxicity (H-HT):	0.378	Drug-induced Liver Injury (DILI):	0.626
AMES Toxicity:	0.58	Rat Oral Acute Toxicity:	0.106
Maximum Recommended Daily Dose:	0.471	Skin Sensitization:	0.847
Carcinogencity:	0.257	Eye Corrosion:	0.007
Eye Irritation:	0.973	Respiratory Toxicity:	0.218
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.461
Hematotoxicity:	0.037	Drug-induced Nephrotoxicity:	0.126
Genotoxicity:	0.716	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.15	Hek293 Cytotoxicity:	0.423
BCF:	0.548 ? 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:	3.021 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.234 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.561 ? 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
NPO7353	Euphorbia paralias	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7353	Euphorbia paralias	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7353	Euphorbia paralias	Species	Euphorbiaceae	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 NPC543836 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	21572
0.1-0.2	25211
0.2-0.3	2191
0.3-0.4	613
0.4-0.5	224
0.5-0.6	32
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
0.7632	Intermediate Similarity	NPC197285
0.6912	Remote Similarity	NPC125062
0.6447	Remote Similarity	NPC54802
0.6447	Remote Similarity	NPC197304
0.6364	Remote Similarity	NPC276222
0.6364	Remote Similarity	NPC274618
0.6364	Remote Similarity	NPC118284
0.6364	Remote Similarity	NPC608147
0.6098	Remote Similarity	NPC21100
0.6	Remote Similarity	NPC601586
0.5952	Remote Similarity	NPC601710
0.593	Remote Similarity	NPC4390
0.5926	Remote Similarity	NPC254306
0.5773	Remote Similarity	NPC219043
0.5634	Remote Similarity	NPC28274
0.5543	Remote Similarity	NPC153755
0.5517	Remote Similarity	NPC223747
0.5507	Remote Similarity	NPC179271
0.5479	Remote Similarity	NPC54394
0.5479	Remote Similarity	NPC159103
0.5455	Remote Similarity	NPC262699
0.5455	Remote Similarity	NPC203050
0.5455	Remote Similarity	NPC131217
0.5455	Remote Similarity	NPC225434
0.5444	Remote Similarity	NPC471079
0.5444	Remote Similarity	NPC187379
0.5441	Remote Similarity	NPC116775
0.5385	Remote Similarity	NPC67326
0.5377	Remote Similarity	NPC192539
0.5362	Remote Similarity	NPC20791
0.5333	Remote Similarity	NPC252933
0.5333	Remote Similarity	NPC133953
0.5312	Remote Similarity	NPC476472
0.5312	Remote Similarity	NPC294815
0.5312	Remote Similarity	NPC16194
0.5278	Remote Similarity	NPC219330
0.5205	Remote Similarity	NPC50403
0.5205	Remote Similarity	NPC241838
0.52	Remote Similarity	NPC609179
0.52	Remote Similarity	NPC610401
0.5132	Remote Similarity	NPC183950
0.5132	Remote Similarity	NPC279989

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC543836 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5393
0.1-0.2	3702
0.2-0.3	41
0.3-0.4	12
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
0.5362	Remote Similarity	NPD1512	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