NPASS Compound

Natural Product: NPC502243

Natural Product ID	NPC502243
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3~{S})-5-[[(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-hydroxy-3-methyl-5-oxo-pentanoic acid
IUPAC Name	(3~{S})-5-[[(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-hydroxy-3-methyl-5-oxo-pentanoic 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 70 73 0 0 0 0 0 0 0 0999 V2000 7.1345 1.6871 2.7415 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9007 1.0621 1.3641 C 0 0 2 0 0 0 0 0 0 0 0 0 7.8320 0.0704 1.1227 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0878 2.1786 0.3637 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4624 2.7543 0.4415 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2836 2.2996 1.2595 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8240 3.7928 -0.3954 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4874 0.5553 1.3427 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1050 -0.0945 0.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9469 -0.1966 -0.8393 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8300 -0.5965 -0.1211 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5562 -1.2004 -1.3600 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1514 -1.7265 -1.4890 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2648 -0.6686 -1.3341 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0166 -1.0617 -1.8600 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0363 -0.3882 -1.3594 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1273 -0.8084 -0.6575 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0991 0.1612 -0.3040 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2290 -0.1694 0.4016 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4918 -1.4580 0.8113 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5662 -2.4180 0.4828 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8134 -3.7195 0.8867 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4139 -2.0857 -0.2362 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5208 -3.1124 -0.5321 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6317 -1.7805 1.5200 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8408 -2.9831 1.8814 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5337 -0.7664 1.8237 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2326 0.4973 1.3972 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1525 1.5923 1.6941 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3128 1.4096 2.3679 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1912 2.4698 2.6488 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8845 3.7449 2.2357 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7590 4.8044 2.5143 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7063 3.9384 1.5502 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8508 2.8967 1.2784 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1194 0.7463 0.7184 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1871 -0.8499 -3.3767 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5512 0.5035 -3.5149 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2677 -1.7654 -3.8401 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2143 -1.0061 -4.5697 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9859 -2.4984 -2.7493 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4443 -3.7768 -2.5182 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1492 1.4850 3.1129 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9075 2.7603 2.6558 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4027 1.2233 3.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1811 0.0910 0.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9331 1.8625 -0.6816 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3340 2.9555 0.6222 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7802 3.8364 -0.7368 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7844 1.4229 1.5017 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3126 -0.1822 2.1516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7817 -0.5256 -2.2172 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2630 -2.0679 -1.4512 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9454 -2.4382 -0.6366 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0435 -2.1523 -1.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9165 1.1652 -0.6111 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8568 -4.4373 0.1714 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9774 -3.6028 0.1596 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4132 -1.0177 2.3721 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6150 0.4415 2.7188 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1093 2.3026 3.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7355 4.6373 2.6971 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4397 4.9308 1.2143 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9233 3.0469 0.7394 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8035 -1.0347 -3.8411 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8401 0.9035 -2.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8063 -2.5196 -4.5128 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8714 -1.5702 -5.0193 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0179 -2.7191 -3.1540 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5021 -4.0107 -1.5550 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 6 2 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 2 8 1 0 8 9 1 0 9 10 2 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 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 2 0 23 24 1 0 20 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 32 34 1 0 34 35 2 0 28 36 1 0 15 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 39 41 1 0 41 42 1 0 41 13 1 0 23 17 1 0 35 29 1 0 36 19 1 0 1 43 1 0 1 44 1 0 1 45 1 0 3 46 1 0 4 47 1 0 4 48 1 0 7 49 1 0 8 50 1 0 8 51 1 0 12 52 1 0 12 53 1 0 13 54 1 1 15 55 1 6 18 56 1 0 22 57 1 0 24 58 1 0 27 59 1 0 30 60 1 0 31 61 1 0 33 62 1 0 34 63 1 0 35 64 1 0 37 65 1 6 38 66 1 0 39 67 1 6 40 68 1 0 41 69 1 6 42 70 1 0 M END

Standard InCHIKey	UVSMDMAXSKHOQT-GFWYNXLGSA-N
Standard InCHI	InChI=1S/C27H28O15/c1-27(38,8-18(30)31)9-19(32)39-10-17-22(34)24(36)25(37)26(42-17)41-16-7-15-20(23(35)21(16)33)13(29)6-14(40-15)11-2-4-12(28)5-3-11/h2-7,17,22,24-26,28,33-38H,8-10H2,1H3,(H,30,31)/t17-,22-,24+,25+,26-,27+/m1/s1
SMILES	C[C@](O)(CC(=O)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:	592.14	Volume:	546.811 ? Van der Waals volume.
Dense:	1.083	LogP:	0.514 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.032 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.472 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	26.0
TPSA:	253.88 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.119	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.433	Fsp³:	0.37
MCE-18:	101.378 ? 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:	0.39	Fluc inhibitor:	0.308 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.957 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.826 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.037	Promiscuous compounds:	0.503

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.254	MDCK Permeability:	-5.315
Pgp-inhibitor:	0.0	Pgp-substrate:	0.065
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):	0.019
20% Bioavailability (F20%):	0.902	30% Bioavailability (F30%):	0.917
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.567
Plasma Protein Binding (PPB):	84.55%	Volume Distribution (VD):	-0.18
Fu:	13.291% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.012
BSEP inhibitor:	0.014

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:	0.982
HLM stability:	0.0 ? 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):

2.832

Half-life (T1/2):

3.057

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.026
Human Hepatotoxicity (H-HT):	0.93	Drug-induced Liver Injury (DILI):	0.455
AMES Toxicity:	0.289	Rat Oral Acute Toxicity:	0.375
Maximum Recommended Daily Dose:	0.826	Skin Sensitization:	0.988
Carcinogencity:	0.604	Eye Corrosion:	0.0
Eye Irritation:	0.784	Respiratory Toxicity:	0.263
Drug-induced Neurotoxicity:	0.009	Ototoxicity:	0.912
Hematotoxicity:	0.091	Drug-induced Nephrotoxicity:	0.961
Genotoxicity:	0.98	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.118	Hek293 Cytotoxicity:	0.225
BCF:	0.189 ? 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:	2.594 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.967 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.119 ? 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
NPO45813	Frullania muscicola	Species	Frullaniaceae	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 NPC502243 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	9464
0.1-0.2	36350
0.2-0.3	3130
0.3-0.4	666
0.4-0.5	200
0.5-0.6	33
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
0.6907	Remote Similarity	NPC64051
0.6863	Remote Similarity	NPC121703
0.6593	Remote Similarity	NPC146792
0.6458	Remote Similarity	NPC477848
0.6316	Remote Similarity	NPC43211
0.6289	Remote Similarity	NPC172807
0.6275	Remote Similarity	NPC229409
0.6078	Remote Similarity	NPC46202
0.6	Remote Similarity	NPC277532
0.5833	Remote Similarity	NPC58716
0.5789	Remote Similarity	NPC45618
0.5755	Remote Similarity	NPC270675
0.5755	Remote Similarity	NPC195685
0.5641	Remote Similarity	NPC209550
0.5631	Remote Similarity	NPC44931
0.5596	Remote Similarity	NPC472994
0.5588	Remote Similarity	NPC254540
0.5556	Remote Similarity	NPC237435
0.5536	Remote Similarity	NPC472993
0.5517	Remote Similarity	NPC480445
0.5505	Remote Similarity	NPC298171
0.5495	Remote Similarity	NPC482721
0.5495	Remote Similarity	NPC599948
0.549	Remote Similarity	NPC211594
0.5364	Remote Similarity	NPC101636
0.5354	Remote Similarity	NPC84265
0.5294	Remote Similarity	NPC480444
0.5273	Remote Similarity	NPC477629
0.5204	Remote Similarity	NPC331652
0.5196	Remote Similarity	NPC115760
0.5152	Remote Similarity	NPC39360
0.5152	Remote Similarity	NPC29763
0.5152	Remote Similarity	NPC210003
0.5149	Remote Similarity	NPC27942
0.514	Remote Similarity	NPC473512
0.514	Remote Similarity	NPC129827
0.5133	Remote Similarity	NPC603856
0.51	Remote Similarity	NPC93337
0.505	Remote Similarity	NPC105025
0.5046	Remote Similarity	NPC472508
0.5046	Remote Similarity	NPC153755
0.5045	Remote Similarity	NPC479766

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC502243 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3021
0.1-0.2	6006
0.2-0.3	113
0.3-0.4	5
0.4-0.5	4
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
0.5556	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