NPASS Compound

Natural Product: NPC561822

Natural Product ID	NPC561822
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2~{R},3~{S},4~{S},5~{R},6~{S})-6-[5,6-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methyl acetate
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-6-[5,6-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methyl acetate
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 62 0 0 0 0 0 0 0 0999 V2000 -4.7475 4.3010 0.1051 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0156 2.8256 0.1261 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0768 2.4045 -0.3955 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1608 1.9238 0.6849 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3081 0.5321 0.7589 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3775 -0.0463 -0.6106 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2436 0.2185 -1.3601 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2702 -0.7479 -1.2947 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9511 -1.0506 0.0211 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7470 -0.9443 0.6568 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4165 -0.4948 0.0685 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6159 -0.4111 0.7780 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6658 -0.7824 2.1068 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4978 -1.2382 2.7131 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6006 -1.5991 4.0498 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6660 -1.3086 1.9868 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7934 -1.7700 2.6467 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8385 -0.7067 2.8216 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9111 -1.0370 4.0265 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9616 -0.2374 2.1308 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8768 0.1185 0.8269 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0437 0.6103 0.0945 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2756 0.7453 0.6514 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3683 1.2200 -0.0837 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6278 1.3498 0.5145 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2367 1.5674 -1.3964 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2895 2.0465 -2.1804 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9835 1.4281 -1.9567 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8330 1.7807 -3.3033 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8999 0.9642 -1.2510 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7165 0.0160 0.2150 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6966 -2.0596 -1.9647 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2096 -2.1208 -3.2640 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2048 -2.0614 -1.9572 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6501 -3.3569 -2.1881 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6389 -1.5466 -0.5968 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9944 -1.8172 -0.3802 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6311 4.5636 -0.9798 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5921 4.8355 0.5581 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7895 4.5437 0.5772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4444 0.1513 1.3549 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2110 0.2219 1.3254 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2442 0.3907 -1.1425 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4024 -0.3628 -1.8920 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4018 -0.1999 -0.9662 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9067 -2.5175 4.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5709 -2.0911 2.0885 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8859 -0.1796 2.7008 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4590 0.4939 1.6754 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8842 0.6950 1.2266 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2253 1.7084 -1.9932 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4261 1.2919 -3.9556 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9090 0.8503 -1.6810 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3339 -2.9319 -1.3818 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9617 -2.3998 -3.8526 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5951 -1.3408 -2.7086 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6209 -3.4221 -2.1350 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0671 -2.0237 0.2019 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5413 -0.9925 -0.3850 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 13 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 24 26 2 0 26 27 1 0 26 28 1 0 28 29 1 0 28 30 2 0 21 31 1 0 8 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 6 1 0 16 10 1 0 30 22 1 0 31 12 1 0 1 38 1 0 1 39 1 0 1 40 1 0 5 41 1 0 5 42 1 0 6 43 1 6 8 44 1 6 11 45 1 0 15 46 1 0 17 47 1 0 20 48 1 0 23 49 1 0 25 50 1 0 27 51 1 0 29 52 1 0 30 53 1 0 32 54 1 1 33 55 1 0 34 56 1 6 35 57 1 0 36 58 1 1 37 59 1 0 M END

Standard InCHIKey	SYZSJYREQFIQIC-UGPBBDQXSA-N
Standard InCHI	InChI=1S/C23H22O14/c1-7(24)34-6-15-19(30)21(32)22(33)23(37-15)36-14-5-13-16(20(31)18(14)29)9(25)4-12(35-13)8-2-10(26)17(28)11(27)3-8/h2-5,15,19,21-23,26-33H,6H2,1H3/t15-,19-,21+,22-,23-/m1/s1
SMILES	CC(=O)OC[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC(O)=C(O)C(O)=C2)O3)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	522.1	Volume:	471.473 ? Van der Waals volume.
Dense:	1.107	LogP:	0.292 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.734 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.33 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	236.81 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.159	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.247	Fsp³:	0.304
MCE-18:	96.667 ? 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:	0.686	Fluc inhibitor:	0.173 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.948 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.922 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.09	Promiscuous compounds:	0.873

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.557	MDCK Permeability:	-5.11
Pgp-inhibitor:	0.0	Pgp-substrate:	0.188
PAMPA:	0.999 ? 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):	0.321
20% Bioavailability (F20%):	0.954	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.838
Plasma Protein Binding (PPB):	79.639%	Volume Distribution (VD):	0.006
Fu:	19.062% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.972
BSEP inhibitor:	0.007

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.021
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.013
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.051 ? 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):

2.926

Half-life (T1/2):

3.455

ADMET: Toxicity

hERG Blockers:	0.01	hERG Blockers (10um):	0.447
Human Hepatotoxicity (H-HT):	0.368	Drug-induced Liver Injury (DILI):	0.969
AMES Toxicity:	0.886	Rat Oral Acute Toxicity:	0.087
Maximum Recommended Daily Dose:	0.164	Skin Sensitization:	1.0
Carcinogencity:	0.098	Eye Corrosion:	0.0
Eye Irritation:	0.902	Respiratory Toxicity:	0.014
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.887
Hematotoxicity:	0.027	Drug-induced Nephrotoxicity:	0.051
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.017
A549 Cytotoxicity:	0.977	Hek293 Cytotoxicity:	0.13
BCF:	0.452 ? 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:	3.061 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.497 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.985 ? 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
NPO63799	Halophila ovalis	Species	Hydrocharitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC561822 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	14799
0.1-0.2	31364
0.2-0.3	2820
0.3-0.4	613
0.4-0.5	206
0.5-0.6	43
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
0.686	Remote Similarity	NPC254540
0.6744	Remote Similarity	NPC477848
0.6627	Remote Similarity	NPC58716
0.6552	Remote Similarity	NPC211594
0.6364	Remote Similarity	NPC172807
0.619	Remote Similarity	NPC45618
0.6118	Remote Similarity	NPC146792
0.6071	Remote Similarity	NPC473043
0.5859	Remote Similarity	NPC603856
0.5833	Remote Similarity	NPC229409
0.5745	Remote Similarity	NPC210073
0.5579	Remote Similarity	NPC3583
0.5567	Remote Similarity	NPC470443
0.5543	Remote Similarity	NPC190003
0.5521	Remote Similarity	NPC204693
0.551	Remote Similarity	NPC209296
0.5506	Remote Similarity	NPC245014
0.5495	Remote Similarity	NPC181616
0.549	Remote Similarity	NPC599948
0.5484	Remote Similarity	NPC116864
0.5484	Remote Similarity	NPC244776
0.5464	Remote Similarity	NPC46202
0.5464	Remote Similarity	NPC64051
0.5417	Remote Similarity	NPC233994
0.5417	Remote Similarity	NPC22062
0.5417	Remote Similarity	NPC473634
0.5417	Remote Similarity	NPC138811
0.5408	Remote Similarity	NPC65711
0.5385	Remote Similarity	NPC237435
0.5347	Remote Similarity	NPC298171
0.5326	Remote Similarity	NPC43211
0.5312	Remote Similarity	NPC44931
0.5312	Remote Similarity	NPC227508
0.53	Remote Similarity	NPC270675
0.53	Remote Similarity	NPC488089
0.53	Remote Similarity	NPC195685
0.5281	Remote Similarity	NPC19709
0.5253	Remote Similarity	NPC211532
0.5253	Remote Similarity	NPC488364
0.5208	Remote Similarity	NPC609888
0.52	Remote Similarity	NPC473623
0.52	Remote Similarity	NPC483707
0.5196	Remote Similarity	NPC101636
0.5155	Remote Similarity	NPC275454
0.5146	Remote Similarity	NPC472994
0.5111	Remote Similarity	NPC261866
0.5109	Remote Similarity	NPC201292
0.5094	Remote Similarity	NPC472993
0.5055	Remote Similarity	NPC189142
0.5055	Remote Similarity	NPC77660
0.5048	Remote Similarity	NPC11468

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC561822 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4609
0.1-0.2	4460
0.2-0.3	70
0.3-0.4	5
0.4-0.5	4
0.5-0.6	2
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
0.551	Remote Similarity	NPD7054	Phase 4
0.5385	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