NPASS Compound

Natural Product: NPC510837

Natural Product ID	NPC510837
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~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[3-(4-methoxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-yl]methyl acetate
IUPAC Name	[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[3-(4-methoxyphenyl)-4-oxo-chromen-7-yl]oxy-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 58 61 0 0 0 0 0 0 0 0999 V2000 10.4281 -0.1595 1.3179 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8843 -0.5341 0.0684 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5485 -0.3425 -0.1709 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0125 -0.7039 -1.3823 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6635 -0.5204 -1.6499 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8232 0.0267 -0.7150 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4030 0.2394 -0.9467 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8853 0.7816 -2.1032 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5982 0.9606 -2.2813 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7126 0.6283 -1.3530 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3785 0.8252 -1.5638 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5874 0.4849 -0.6024 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9156 0.7040 -0.8654 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0294 0.4495 -0.0751 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8602 -0.4098 -0.8004 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0953 -0.5938 -0.2315 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0469 -1.2911 1.0949 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3152 -1.4768 1.6798 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3559 -2.2001 1.1239 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6758 -2.3463 1.8152 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1633 -2.7407 0.0056 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8712 0.6999 -0.0837 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0459 1.0317 1.2586 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9768 1.7911 -0.6836 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6080 1.4710 -1.9885 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7173 1.8006 0.1542 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9818 1.9809 1.4997 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1450 -0.0619 0.5787 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2096 -0.2698 0.8111 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1264 0.0776 -0.1577 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4945 -0.1173 0.0422 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8776 -0.6107 1.1109 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3918 0.3864 0.5098 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7376 0.2044 0.7793 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2879 0.9531 1.3990 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5057 -0.4265 1.3303 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8460 -0.6742 2.1002 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6855 -1.1364 -2.1166 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2960 -0.8199 -2.6119 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6166 1.0544 -2.8661 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0142 1.2588 -2.4927 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7438 0.0082 0.8915 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6781 -1.2252 -0.9324 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4457 -0.7075 1.8399 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5688 -2.2858 1.0410 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1880 -3.2407 1.3603 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5620 -2.5468 2.8906 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3434 -1.4919 1.6174 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8559 0.6735 -0.5615 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3741 1.9690 1.2941 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4451 2.7865 -0.6128 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1396 0.7459 -2.3809 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1055 2.6420 -0.1883 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1200 2.0340 1.9692 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8714 -0.3418 1.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5058 -0.7021 1.7546 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7862 0.8185 1.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1416 0.4897 1.7252 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 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 1 0 18 19 1 0 19 20 1 0 19 21 2 0 16 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 12 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 6 33 1 0 33 34 2 0 34 3 1 0 31 7 1 0 30 10 1 0 26 14 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 5 39 1 0 8 40 1 0 11 41 1 0 14 42 1 1 16 43 1 6 17 44 1 0 17 45 1 0 20 46 1 0 20 47 1 0 20 48 1 0 22 49 1 6 23 50 1 0 24 51 1 6 25 52 1 0 26 53 1 6 27 54 1 0 28 55 1 0 29 56 1 0 33 57 1 0 34 58 1 0 M END

Standard InCHIKey	HZJBDSMAAFNHHL-LKAHAZCJSA-N
Standard InCHI	InChI=1S/C24H24O10/c1-12(25)31-11-19-21(27)22(28)23(29)24(34-19)33-15-7-8-16-18(9-15)32-10-17(20(16)26)13-3-5-14(30-2)6-4-13/h3-10,19,21-24,27-29H,11H2,1-2H3/t19-,21+,22-,23+,24+/m0/s1
SMILES	COC1=CC=C(C2=COC3=CC(O[C@@H]4O[C@@H](COC(C)=O)[C@@H](O)[C@H](O)[C@H]4O)=CC=C3C2=O)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	472.14	Volume:	453.608 ? Van der Waals volume.
Dense:	1.041	LogP:	1.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.572 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.4 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	25.0
TPSA:	144.89 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.448	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.687	Fsp³:	0.333
MCE-18:	82.812 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.573	Fluc inhibitor:	0.651 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.915 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.772 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.058	Promiscuous compounds:	0.139

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.844	MDCK Permeability:	-5.077
Pgp-inhibitor:	0.043	Pgp-substrate:	0.281
PAMPA:	0.971 ? 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):	0.821
20% Bioavailability (F20%):	0.372	30% Bioavailability (F30%):	0.913
50% Bioavailability (F50%):	0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.212
Plasma Protein Binding (PPB):	88.095%	Volume Distribution (VD):	-0.47
Fu:	10.703% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.12
BSEP inhibitor:	0.641

ADMET: Metabolism

CYP1A2-inhibitor:	0.855	CYP1A2-substrate:	0.045
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.025	CYP2C9-substrate:	0.03
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.918
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

2.478

Half-life (T1/2):

2.052

ADMET: Toxicity

hERG Blockers:	0.102	hERG Blockers (10um):	0.332
Human Hepatotoxicity (H-HT):	0.615	Drug-induced Liver Injury (DILI):	0.981
AMES Toxicity:	0.924	Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.055	Skin Sensitization:	0.81
Carcinogencity:	0.477	Eye Corrosion:	0.0
Eye Irritation:	0.363	Respiratory Toxicity:	0.02
Drug-induced Neurotoxicity:	0.07	Ototoxicity:	0.758
Hematotoxicity:	0.334	Drug-induced Nephrotoxicity:	0.845
Genotoxicity:	0.809	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.092	Hek293 Cytotoxicity:	0.12
BCF:	0.622 ? 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:	3.385 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.828 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.313 ? 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
NPO21579	Ononis speciosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8277313]
NPO21579	Ononis speciosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21579	Ononis speciosa	Species	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 NPC510837 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	14598
0.1-0.2	31457
0.2-0.3	3041
0.3-0.4	595
0.4-0.5	123
0.5-0.6	26
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
0.7792	Intermediate Similarity	NPC43761
0.7703	Intermediate Similarity	NPC45165
0.7534	Intermediate Similarity	NPC25547
0.7011	Intermediate Similarity	NPC51326
0.6778	Remote Similarity	NPC235575
0.6709	Remote Similarity	NPC211014
0.6667	Remote Similarity	NPC231194
0.6506	Remote Similarity	NPC229729
0.642	Remote Similarity	NPC161749
0.6375	Remote Similarity	NPC135345
0.6364	Remote Similarity	NPC475155
0.625	Remote Similarity	NPC487214
0.6118	Remote Similarity	NPC601607
0.5972	Remote Similarity	NPC136095
0.5942	Remote Similarity	NPC182428
0.5909	Remote Similarity	NPC211594
0.5833	Remote Similarity	NPC603782
0.5765	Remote Similarity	NPC73511
0.5647	Remote Similarity	NPC258035
0.5595	Remote Similarity	NPC160515
0.5584	Remote Similarity	NPC254741
0.5529	Remote Similarity	NPC259070
0.5529	Remote Similarity	NPC478528
0.5484	Remote Similarity	NPC303913
0.5455	Remote Similarity	NPC475261
0.5319	Remote Similarity	NPC479405
0.5287	Remote Similarity	NPC105511
0.5263	Remote Similarity	NPC479404
0.5217	Remote Similarity	NPC172807
0.5161	Remote Similarity	NPC254540
0.5161	Remote Similarity	NPC487212
0.5132	Remote Similarity	NPC181124
0.5132	Remote Similarity	NPC186507
0.5068	Remote Similarity	NPC120924
0.5067	Remote Similarity	NPC185607
0.5065	Remote Similarity	NPC471590
0.5052	Remote Similarity	NPC46202
0.5051	Remote Similarity	NPC488089
0.5047	Remote Similarity	NPC473895

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC510837 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3891
0.1-0.2	5129
0.2-0.3	116
0.3-0.4	9
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.642	Remote Similarity	NPD4381	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