NPASS Compound

Natural Product: NPC539653

Natural Product ID	NPC539653
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-hydroxy-8-[(2~{S},3~{S},4~{R},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]-3-[4-[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name	7-hydroxy-8-[(2~{S},3~{S},4~{R},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]-3-[4-[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]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 71 75 0 0 0 0 0 0 0 0999 V2000 0.2979 2.5413 -2.1923 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1455 1.8460 -1.5543 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6751 0.9142 -0.6545 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7709 0.7087 -0.4183 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2915 -0.5530 -0.3515 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6570 -0.7510 -0.1299 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5096 0.3088 0.0262 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8520 0.1410 0.2443 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5885 -1.0348 0.3470 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.1161 -1.1392 1.6265 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4690 -1.3287 1.6727 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8745 -1.2893 3.1509 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2119 -2.2954 3.8258 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1332 -0.1526 0.9533 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.5071 -0.1426 1.2125 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8450 -0.3289 -0.5081 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7874 0.8872 -1.1899 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6380 -1.1736 -0.7282 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.9072 -2.5137 -0.9383 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9596 1.5927 -0.0450 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6229 1.7782 -0.2621 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6229 0.1755 0.0219 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8999 0.3687 -0.1975 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3838 1.2443 -1.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7431 1.3899 -1.2210 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6665 0.5615 -0.4575 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0230 -0.6390 -0.1763 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7874 -1.5986 0.4182 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8632 -2.8300 -0.4559 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5468 -3.2819 -0.6176 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1519 -1.0998 0.7468 C 0 0 1 0 0 0 0 0 0 0 0 0 8.0518 -1.2136 -0.3367 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1935 0.2443 1.3950 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0927 0.1049 2.7705 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0927 1.1659 0.8563 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0736 1.1451 1.7808 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2127 2.3195 -2.1190 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5632 2.4436 -2.2754 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3372 3.1222 -2.8585 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9656 2.9747 -2.6795 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4923 2.0390 -1.7757 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6374 -1.4110 -0.4715 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9745 -1.7799 -0.0937 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9156 -1.9018 0.2254 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7533 -2.2897 1.2288 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6126 -0.2992 3.5568 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9860 -1.3938 3.2192 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1688 -3.1151 3.2697 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6444 0.7736 1.2973 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6756 0.4914 1.9789 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7301 -0.8726 -0.9435 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8236 0.6664 -2.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1502 -0.8050 -1.6777 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4911 -2.5672 -1.7478 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6343 2.4249 0.0779 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1697 2.7787 -0.3216 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2741 -0.5564 0.7284 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5815 0.4276 -1.0826 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2693 -1.9046 1.3711 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2749 -2.6054 -1.4528 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4326 -3.5973 0.0929 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1436 -3.3533 0.2940 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5739 -1.8264 1.5053 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7551 -0.5376 -0.2800 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2058 0.6801 1.1877 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3269 0.9489 3.2296 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5677 2.1598 0.7259 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9439 2.0255 2.2020 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9148 3.3796 -2.5193 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7184 3.8512 -3.5627 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2441 3.5569 -3.2126 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 4 5 2 0 5 6 1 0 6 7 2 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 11 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 7 20 1 0 20 21 2 0 3 22 2 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 25 37 1 0 37 38 1 0 37 39 2 0 39 40 1 0 40 41 2 0 41 2 1 0 21 4 1 0 41 24 1 0 18 9 1 0 35 26 1 0 5 42 1 0 6 43 1 0 9 44 1 6 11 45 1 6 12 46 1 0 12 47 1 0 13 48 1 0 14 49 1 1 15 50 1 0 16 51 1 6 17 52 1 0 18 53 1 6 19 54 1 0 20 55 1 0 21 56 1 0 22 57 1 0 26 58 1 6 28 59 1 1 29 60 1 0 29 61 1 0 30 62 1 0 31 63 1 1 32 64 1 0 33 65 1 1 34 66 1 0 35 67 1 6 36 68 1 0 38 69 1 0 39 70 1 0 40 71 1 0 M END

Standard InCHIKey	GZFMKWZQYRIRBD-YLHZMVMQSA-N
Standard InCHI	InChI=1S/C27H30O14/c28-7-15-19(32)21(34)23(36)26(40-15)17-14(30)6-5-12-18(31)13(9-38-25(12)17)10-1-3-11(4-2-10)39-27-24(37)22(35)20(33)16(8-29)41-27/h1-6,9,15-16,19-24,26-30,32-37H,7-8H2/t15-,16-,19+,20-,21-,22+,23-,24-,26-,27-/m0/s1
SMILES	O=C1C(C2=CC=C(O[C@H]3O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]3O)C=C2)=COC2=C([C@@H]3O[C@@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)C(O)=CC=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	578.16	Volume:	534.737 ? Van der Waals volume.
Dense:	1.081	LogP:	-1.269 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.005 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.829 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	30.0
TPSA:	239.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	9.0	Rings:	5.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.152	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.609	Fsp³:	0.444
MCE-18:	115.923 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.669	Fluc inhibitor:	0.213 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.934 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.44 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.319	Promiscuous compounds:	0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.827	MDCK Permeability:	-4.953
Pgp-inhibitor:	0.0	Pgp-substrate:	0.627
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):	1.0
20% Bioavailability (F20%):	0.961	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.143
Plasma Protein Binding (PPB):	80.534%	Volume Distribution (VD):	-0.079
Fu:	19.801% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.724
OATP1B3 inhibitor:	0.973	BCRP inhibitor:	0.007
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.441	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.993
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.002 ? 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):

1.436

Half-life (T1/2):

3.63

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.723	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.953	Rat Oral Acute Toxicity:	0.028
Maximum Recommended Daily Dose:	0.006	Skin Sensitization:	0.991
Carcinogencity:	0.041	Eye Corrosion:	0.0
Eye Irritation:	0.033	Respiratory Toxicity:	0.004
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.985
Hematotoxicity:	0.3	Drug-induced Nephrotoxicity:	0.97
Genotoxicity:	0.61	RPMI-8226 Immunitoxicity:	0.383
A549 Cytotoxicity:	0.727	Hek293 Cytotoxicity:	0.136
BCF:	0.507 ? 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:	3.251 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.065 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.024 ? 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
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28089	Pueraria pseudohirsuta	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28089	Pueraria pseudohirsuta	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	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 NPC539653 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	16627
0.1-0.2	29625
0.2-0.3	2745
0.3-0.4	767
0.4-0.5	74
0.5-0.6	16
0.6-0.7	4
0.7-0.8	1
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
0.7342	Intermediate Similarity	NPC124478
0.6667	Remote Similarity	NPC258035
0.6092	Remote Similarity	NPC161749
0.6092	Remote Similarity	NPC603782
0.6047	Remote Similarity	NPC45165
0.5862	Remote Similarity	NPC135345
0.5745	Remote Similarity	NPC607879
0.573	Remote Similarity	NPC156457
0.5682	Remote Similarity	NPC177308
0.5667	Remote Similarity	NPC73511
0.5652	Remote Similarity	NPC229729
0.5556	Remote Similarity	NPC105511
0.5521	Remote Similarity	NPC603300
0.5341	Remote Similarity	NPC25547
0.5319	Remote Similarity	NPC601607
0.5269	Remote Similarity	NPC205076
0.5217	Remote Similarity	NPC197896
0.5217	Remote Similarity	NPC313163
0.5109	Remote Similarity	NPC211014
0.5106	Remote Similarity	NPC100720
0.5104	Remote Similarity	NPC307518

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC539653 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3617
0.1-0.2	5439
0.2-0.3	81
0.3-0.4	10
0.4-0.5	0
0.5-0.6	1
0.6-0.7	1
0.7-0.8	1
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
0.7342	Intermediate Similarity	NPD4380	Phase 2
0.6092	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5165	Remote Similarity	NPD3818	Discontinued

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