NPASS Compound

Natural Product: NPC519435

Natural Product ID	NPC519435
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S},3~{S},4~{R},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-7-sulfooxy-chromen-3-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{R},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-7-sulfooxy-chromen-3-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
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 56 59 0 0 0 0 0 0 0 0999 V2000 -6.1708 0.2577 0.9728 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0584 0.6092 0.4953 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6139 1.8682 0.8196 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2548 -0.2861 -0.3795 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1028 0.3665 -0.7339 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0059 -0.4222 -0.8902 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2643 -0.4325 0.3406 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1155 -0.3182 0.3456 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7327 0.8769 0.4381 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0914 2.1555 0.5580 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1986 2.4284 0.8710 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7325 3.7117 0.9148 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9419 4.7819 0.6336 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4905 6.0615 0.6813 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3688 4.5677 0.3125 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1488 5.6839 0.0315 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8798 3.2894 0.2737 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0821 0.8232 0.4121 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7640 -0.2639 0.3117 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1565 -0.2473 0.2908 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8959 -1.3993 0.1844 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3033 -1.3573 0.1653 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2281 -1.4469 1.5712 S 0 0 0 0 0 0 0 0 0 0 0 0 6.3494 -1.2886 2.7994 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8936 -2.8048 1.7062 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3815 -0.2333 1.6441 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2823 -2.6291 0.0933 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9049 -2.6822 0.1109 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2094 -3.8863 0.0232 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1841 -1.5157 0.2181 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8047 -1.5303 0.2373 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2075 -2.6179 0.1602 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3591 -1.8065 -1.3816 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2585 -1.5808 -2.4627 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1379 -2.5267 -0.3433 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0094 -3.4566 -0.9119 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9130 -1.4990 0.4596 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0686 -2.0785 0.9546 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2310 2.5608 1.2243 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9169 -0.5426 -1.2366 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3190 -0.0055 -1.6535 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8381 1.6358 1.1296 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7860 3.8495 1.1777 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5429 6.5684 -0.1875 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6531 6.0886 0.8033 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9214 3.1758 0.0145 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6895 0.6818 0.3585 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0155 -0.3646 0.8934 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8628 -3.5483 0.0086 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1764 -4.4372 0.8842 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5154 -2.3002 -1.8324 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6925 -1.1951 -3.1792 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4768 -3.0853 0.3334 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6773 -4.3795 -0.8557 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2940 -1.1421 1.3064 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4323 -2.7320 0.2857 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 1 0 15 17 2 0 9 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 2 0 23 26 1 0 21 27 2 0 27 28 1 0 28 29 1 0 28 30 2 0 30 31 1 0 31 32 2 0 6 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 37 4 1 0 31 8 1 0 17 10 1 0 30 19 1 0 3 39 1 0 4 40 1 6 6 41 1 6 11 42 1 0 12 43 1 0 14 44 1 0 16 45 1 0 17 46 1 0 20 47 1 0 26 48 1 0 27 49 1 0 29 50 1 0 33 51 1 6 34 52 1 0 35 53 1 1 36 54 1 0 37 55 1 1 38 56 1 0 M END

Standard InCHIKey	UZHUMGQOPXDLRD-OAWSQYKSSA-N
Standard InCHI	InChI=1S/C21H18O16S/c22-8-2-1-6(3-9(8)23)17-18(35-21-16(28)14(26)15(27)19(36-21)20(29)30)13(25)12-10(24)4-7(5-11(12)34-17)37-38(31,32)33/h1-5,14-16,19,21-24,26-28H,(H,29,30)(H,31,32,33)/t14-,15+,16-,19+,21-/m1/s1
SMILES	O=C(O)[C@H]1O[C@@H](OC2=C(C3=CC=C(O)C(O)=C3)OC3=CC(OS(=O)(=O)O)=CC(O)=C3C2=O)[C@H](O)[C@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	558.03	Volume:	472.971 ? Van der Waals volume.
Dense:	1.18	LogP:	-0.788 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.61 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.068 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	27.0
TPSA:	270.95 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	17.0

MedChem Properties

QED Drug-Likeness Score:	0.133	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.249	Fsp³:	0.238
MCE-18:	104.923 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.502	Fluc inhibitor:	0.268 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.923 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.736 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.481	Promiscuous compounds:	0.356

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.58	MDCK Permeability:	-4.938
Pgp-inhibitor:	0.0	Pgp-substrate:	0.073
PAMPA:	1.0 ? 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):	0.814
20% Bioavailability (F20%):	0.921	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.904
Plasma Protein Binding (PPB):	75.708%	Volume Distribution (VD):	-0.466
Fu:	22.4% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.133
OATP1B3 inhibitor:	0.972	BCRP inhibitor:	0.143
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.797
HLM stability:	0.372 ? 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):

1.688

Half-life (T1/2):

3.109

ADMET: Toxicity

hERG Blockers:	0.001	hERG Blockers (10um):	0.004
Human Hepatotoxicity (H-HT):	0.469	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.237	Rat Oral Acute Toxicity:	0.056
Maximum Recommended Daily Dose:	0.436	Skin Sensitization:	1.0
Carcinogencity:	0.012	Eye Corrosion:	0.015
Eye Irritation:	0.837	Respiratory Toxicity:	0.332
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.766
Hematotoxicity:	0.125	Drug-induced Nephrotoxicity:	0.267
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.029
A549 Cytotoxicity:	0.271	Hek293 Cytotoxicity:	0.072
BCF:	0.376 ? 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:	2.845 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.074 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.712 ? 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
NPO14174	Frankenia pulverulenta	Species	Frankeniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14174	Frankenia pulverulenta	Species	Frankeniaceae	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 NPC519435 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	27092
0.1-0.2	20767
0.2-0.3	1409
0.3-0.4	382
0.4-0.5	165
0.5-0.6	35
0.6-0.7	3
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	NPC235260
0.75	Intermediate Similarity	NPC155763
0.6667	Remote Similarity	NPC20505
0.6548	Remote Similarity	NPC138927
0.6092	Remote Similarity	NPC282169
0.5909	Remote Similarity	NPC135277
0.5909	Remote Similarity	NPC49344
0.5747	Remote Similarity	NPC136042
0.5682	Remote Similarity	NPC271692
0.5667	Remote Similarity	NPC608742
0.55	Remote Similarity	NPC605587
0.5495	Remote Similarity	NPC43211
0.5435	Remote Similarity	NPC605784
0.5385	Remote Similarity	NPC210094
0.5333	Remote Similarity	NPC84362
0.5287	Remote Similarity	NPC276222
0.5287	Remote Similarity	NPC274618
0.5287	Remote Similarity	NPC118284
0.5287	Remote Similarity	NPC608147
0.5217	Remote Similarity	NPC237435
0.5165	Remote Similarity	NPC27640
0.5161	Remote Similarity	NPC115760
0.5161	Remote Similarity	NPC610187
0.5111	Remote Similarity	NPC127546
0.5111	Remote Similarity	NPC249281
0.5111	Remote Similarity	NPC57625
0.5111	Remote Similarity	NPC173637
0.5111	Remote Similarity	NPC317489
0.5111	Remote Similarity	NPC223424
0.5111	Remote Similarity	NPC600591
0.5109	Remote Similarity	NPC101191
0.5055	Remote Similarity	NPC145038
0.5055	Remote Similarity	NPC56077
0.5055	Remote Similarity	NPC297987
0.5055	Remote Similarity	NPC281131
0.5055	Remote Similarity	NPC253662
0.5055	Remote Similarity	NPC179950
0.5055	Remote Similarity	NPC88789
0.5055	Remote Similarity	NPC491374
0.5054	Remote Similarity	NPC488071

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC519435 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4730
0.1-0.2	4363
0.2-0.3	51
0.3-0.4	3
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
0.5217	Remote Similarity	NPD4338	Clinical (unspecified phase)

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