NPASS Compound

Natural Product: NPC573112

Natural Product ID	NPC573112
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-[[(2~{R},3~{S},4~{S},5~{S},6~{S})-6-[5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methoxy]-3-oxo-propanoic acid
IUPAC Name	3-[[(2~{R},3~{S},4~{S},5~{S},6~{S})-6-[5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methoxy]-3-oxo-propanoic 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 60 63 0 0 0 0 0 0 0 0999 V2000 -5.3790 2.5655 1.5418 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5209 2.2333 1.1252 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6065 2.6417 1.8829 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6840 1.4431 -0.1177 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3400 1.1506 -0.7161 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3246 1.5852 -0.1234 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1815 0.4400 -1.8637 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0019 0.1042 -2.5059 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0405 -0.7545 -1.7778 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5768 -0.2214 -0.6111 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5082 -0.9541 -0.0783 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2055 -0.4364 1.1692 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0441 -0.0018 1.5375 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1548 -0.0220 0.7238 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3985 0.4348 1.1587 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4724 0.9114 2.4466 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3606 0.9383 3.2801 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4903 1.4303 4.5733 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1366 0.4898 2.8552 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9935 0.4950 3.6401 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6969 1.3624 2.8784 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8048 1.8016 4.0382 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7549 1.3013 1.9856 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6267 0.8140 0.7047 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7544 0.7507 -0.2417 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5328 0.2482 -1.5021 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5734 0.1712 -2.4275 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8459 0.5898 -2.1191 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8511 0.4936 -3.0745 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0648 1.0918 -0.8585 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0245 1.1697 0.0694 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4325 0.3992 0.3538 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9278 -2.4106 0.1390 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0057 -2.4801 1.0281 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4118 -3.0165 -1.1640 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7680 -4.3244 -0.9456 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6116 -2.1598 -1.5905 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1314 -2.5808 -2.7932 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6265 3.5235 2.3737 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2618 0.5098 0.0492 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2825 2.0784 -0.8244 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4640 0.9848 -2.9319 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3065 -0.4817 -3.4299 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1617 -0.9137 -2.4681 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6506 -0.9835 -0.7445 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1156 -0.3936 -0.2930 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9775 0.8148 5.2290 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9294 0.5673 3.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7147 1.6581 2.3335 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5422 -0.0796 -1.7475 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3839 -0.2276 -3.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6199 1.1465 -3.1333 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0663 1.4229 -0.6113 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2524 1.5716 1.0427 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0371 -2.9466 0.5125 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8248 -3.2703 1.6158 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6376 -2.8719 -1.9272 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0578 -4.4900 -0.0190 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3407 -2.1236 -0.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8924 -3.1899 -2.6826 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 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 16 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 28 30 1 0 30 31 2 0 24 32 1 0 11 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 37 9 1 0 19 13 1 0 31 25 1 0 32 15 1 0 3 39 1 0 4 40 1 0 4 41 1 0 8 42 1 0 8 43 1 0 9 44 1 6 11 45 1 6 14 46 1 0 18 47 1 0 20 48 1 0 23 49 1 0 26 50 1 0 27 51 1 0 29 52 1 0 30 53 1 0 31 54 1 0 33 55 1 1 34 56 1 0 35 57 1 6 36 58 1 0 37 59 1 1 38 60 1 0 M END

Standard InCHIKey	SSLQZEOVXSUHHA-MEOHWMTASA-N
Standard InCHI	InChI=1S/C24H22O14/c25-10-3-1-9(2-4-10)12-5-11(26)18-13(36-12)6-14(19(30)21(18)32)37-24-23(34)22(33)20(31)15(38-24)8-35-17(29)7-16(27)28/h1-6,15,20,22-25,30-34H,7-8H2,(H,27,28)/t15-,20-,22+,23+,24-/m1/s1
SMILES	O=C(O)CC(=O)OC[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=C(O)C=C2)O3)[C@@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	534.1	Volume:	486.133 ? Van der Waals volume.
Dense:	1.099	LogP:	0.304 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.051 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.102 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	26.0
TPSA:	233.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.118	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.136	Fsp³:	0.292
MCE-18:	93.032 ? 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:	0.451	Fluc inhibitor:	0.309 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.94 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.849 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.077	Promiscuous compounds:	0.625

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.451	MDCK Permeability:	-5.167
Pgp-inhibitor:	0.0	Pgp-substrate:	0.057
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):	0.003
20% Bioavailability (F20%):	0.052	30% Bioavailability (F30%):	0.223
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.542
Plasma Protein Binding (PPB):	82.687%	Volume Distribution (VD):	-0.084
Fu:	14.763% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.983
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.053
BSEP inhibitor:	0.066

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:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.003 ? 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):

1.821

Half-life (T1/2):

3.262

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.06
Human Hepatotoxicity (H-HT):	0.259	Drug-induced Liver Injury (DILI):	0.828
AMES Toxicity:	0.355	Rat Oral Acute Toxicity:	0.091
Maximum Recommended Daily Dose:	0.156	Skin Sensitization:	0.848
Carcinogencity:	0.135	Eye Corrosion:	0.0
Eye Irritation:	0.614	Respiratory Toxicity:	0.032
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.83
Hematotoxicity:	0.134	Drug-induced Nephrotoxicity:	0.476
Genotoxicity:	0.923	RPMI-8226 Immunitoxicity:	0.045
A549 Cytotoxicity:	0.007	Hek293 Cytotoxicity:	0.071
BCF:	0.23 ? 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:	2.69 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.054 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.397 ? 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
NPO2789	Bryum pseudotriquetrum	Species	Bryaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2789	Bryum pseudotriquetrum	Species	Bryaceae	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 NPC573112 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	17812
0.1-0.2	28811
0.2-0.3	2320
0.3-0.4	656
0.4-0.5	207
0.5-0.6	38
0.6-0.7	8
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8046	Intermediate Similarity	NPC64051
0.7283	Intermediate Similarity	NPC229409
0.7065	Intermediate Similarity	NPC46202
0.6941	Remote Similarity	NPC146792
0.6818	Remote Similarity	NPC43211
0.6778	Remote Similarity	NPC477848
0.6593	Remote Similarity	NPC172807
0.6111	Remote Similarity	NPC58716
0.6067	Remote Similarity	NPC45618
0.6	Remote Similarity	NPC270675
0.6	Remote Similarity	NPC195685
0.5978	Remote Similarity	NPC237435
0.5876	Remote Similarity	NPC44931
0.5865	Remote Similarity	NPC599948
0.5833	Remote Similarity	NPC254540
0.5825	Remote Similarity	NPC472994
0.5755	Remote Similarity	NPC472993
0.5729	Remote Similarity	NPC211594
0.5728	Remote Similarity	NPC298171
0.5714	Remote Similarity	NPC121703
0.5686	Remote Similarity	NPC479766
0.5591	Remote Similarity	NPC84265
0.5579	Remote Similarity	NPC115760
0.5577	Remote Similarity	NPC101636
0.5532	Remote Similarity	NPC27942
0.5481	Remote Similarity	NPC479765
0.5472	Remote Similarity	NPC603856
0.5435	Remote Similarity	NPC331652
0.5376	Remote Similarity	NPC39360
0.5376	Remote Similarity	NPC29763
0.5376	Remote Similarity	NPC210003
0.5347	Remote Similarity	NPC473512
0.5347	Remote Similarity	NPC129827
0.5333	Remote Similarity	NPC477629
0.5319	Remote Similarity	NPC93337
0.5312	Remote Similarity	NPC282169
0.5263	Remote Similarity	NPC105025
0.5244	Remote Similarity	NPC198826
0.5196	Remote Similarity	NPC22062
0.5196	Remote Similarity	NPC473634
0.5196	Remote Similarity	NPC210073
0.5196	Remote Similarity	NPC3583
0.5196	Remote Similarity	NPC138811
0.5192	Remote Similarity	NPC470443
0.5146	Remote Similarity	NPC204693
0.5104	Remote Similarity	NPC245014
0.5102	Remote Similarity	NPC181616
0.5048	Remote Similarity	NPC65711
0.5047	Remote Similarity	NPC80068

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC573112 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3929
0.1-0.2	5125
0.2-0.3	85
0.3-0.4	6
0.4-0.5	3
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
0.5978	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