NPASS Compound

Natural Product: NPC553241

Natural Product ID	NPC553241
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-5-hydroxy-2-(4-methoxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chroman-4-one
IUPAC Name	(2~{S})-5-hydroxy-2-(4-methoxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chroman-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 56 59 0 0 0 0 0 0 0 0999 V2000 9.4562 -1.5428 -1.2750 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5067 -1.7884 -0.2642 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2615 -1.1415 -0.2470 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3561 -1.4064 0.7581 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1161 -0.7885 0.8108 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7430 0.1234 -0.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4233 0.7889 -0.1080 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3812 1.8829 0.9405 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0960 2.6021 0.7469 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0039 3.8534 0.7798 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8941 1.7852 0.5079 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3575 2.3488 0.5659 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5222 3.6943 0.8493 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4874 1.5748 0.3399 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3362 0.2393 0.0579 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3749 -0.6065 -0.1789 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7075 -0.2922 -0.1790 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3924 -1.0917 0.7433 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6632 -1.4125 0.2781 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.4859 -2.0102 1.3956 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6408 -1.1514 2.4681 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2833 -0.1845 -0.3023 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.6738 -0.2368 -0.3566 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6784 0.0096 -1.6930 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3479 -0.7646 -2.6158 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2421 -0.5084 -1.5851 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4738 0.2798 -2.4403 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0414 -0.3047 0.0064 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0866 0.4400 0.2259 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3716 -0.1051 0.1737 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6427 0.3945 -1.1629 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8912 -0.2296 -1.2131 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0761 -1.8338 -2.2611 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3534 -2.1668 -1.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8175 -0.4960 -1.2933 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6354 -2.1219 1.5243 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4062 -1.0019 1.6067 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2163 1.2630 -1.0868 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3870 1.4406 1.9579 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2621 2.5328 0.7497 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6718 4.3704 0.1148 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4697 2.0684 0.3966 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8729 0.7728 0.0441 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5253 -2.2260 -0.4785 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0509 -2.9576 1.7671 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5020 -2.2598 1.0291 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8869 -1.2116 3.1015 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9915 0.6896 0.2962 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0777 0.0730 0.4895 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6947 1.0580 -2.0008 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3213 -0.5839 -2.6020 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1510 -1.5522 -1.9228 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5250 -0.0225 -3.3797 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0957 -1.3715 -0.2180 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3641 1.1101 -1.9296 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6053 -0.0245 -2.0007 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 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 15 28 1 0 28 29 2 0 29 30 1 0 6 31 1 0 31 32 2 0 32 3 1 0 30 7 1 0 29 11 1 0 26 17 1 0 1 33 1 0 1 34 1 0 1 35 1 0 4 36 1 0 5 37 1 0 7 38 1 6 8 39 1 0 8 40 1 0 13 41 1 0 14 42 1 0 17 43 1 1 19 44 1 6 20 45 1 0 20 46 1 0 21 47 1 0 22 48 1 1 23 49 1 0 24 50 1 6 25 51 1 0 26 52 1 6 27 53 1 0 28 54 1 0 31 55 1 0 32 56 1 0 M END

Standard InCHIKey	KEEWIHDTSNESJZ-QFWXNIIVSA-N
Standard InCHI	InChI=1S/C22H24O10/c1-29-11-4-2-10(3-5-11)15-8-14(25)18-13(24)6-12(7-16(18)31-15)30-22-21(28)20(27)19(26)17(9-23)32-22/h2-7,15,17,19-24,26-28H,8-9H2,1H3/t15-,17-,19-,20-,21+,22+/m0/s1
SMILES	COC1=CC=C([C@@H]2CC(=O)C3=C(O)C=C(O[C@@H]4O[C@@H](CO)[C@H](O)[C@H](O)[C@H]4O)C=C3O2)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.14	Volume:	424.289 ? Van der Waals volume.
Dense:	1.056	LogP:	1.458 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.929 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.402 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	155.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.431	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.925	Fsp³:	0.409
MCE-18:	86.29 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.641	Fluc inhibitor:	0.565 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.122 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.431 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.093	Promiscuous compounds:	0.329

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.407	MDCK Permeability:	-5.3
Pgp-inhibitor:	0.063	Pgp-substrate:	0.06
PAMPA:	0.796 ? 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):	0.63
20% Bioavailability (F20%):	0.03	30% Bioavailability (F30%):	0.969
50% Bioavailability (F50%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.144
Plasma Protein Binding (PPB):	90.792%	Volume Distribution (VD):	-0.153
Fu:	8.889% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.991
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.93
BSEP inhibitor:	0.146

ADMET: Metabolism

CYP1A2-inhibitor:	0.01	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.741
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.08
HLM stability:	0.082 ? 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):

3.284

Half-life (T1/2):

2.025

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.181
Human Hepatotoxicity (H-HT):	0.89	Drug-induced Liver Injury (DILI):	0.992
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.23
Maximum Recommended Daily Dose:	0.105	Skin Sensitization:	0.995
Carcinogencity:	0.253	Eye Corrosion:	0.0
Eye Irritation:	0.576	Respiratory Toxicity:	0.306
Drug-induced Neurotoxicity:	0.197	Ototoxicity:	0.896
Hematotoxicity:	0.573	Drug-induced Nephrotoxicity:	0.977
Genotoxicity:	0.954	RPMI-8226 Immunitoxicity:	0.319
A549 Cytotoxicity:	0.874	Hek293 Cytotoxicity:	0.368
BCF:	0.568 ? 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:	3.316 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.99 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.124 ? 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
NPO10448	Prunus cerasoides	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10448	Prunus cerasoides	Species	Rosaceae	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 NPC553241 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	17319
0.1-0.2	26850
0.2-0.3	4420
0.3-0.4	927
0.4-0.5	265
0.5-0.6	44
0.6-0.7	21
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC219163
0.8615	High Similarity	NPC97052
0.8485	Intermediate Similarity	NPC39351
0.8143	Intermediate Similarity	NPC236934
0.7971	Intermediate Similarity	NPC29830
0.7681	Intermediate Similarity	NPC26195
0.7179	Intermediate Similarity	NPC97285
0.6849	Remote Similarity	NPC206378
0.6806	Remote Similarity	NPC170475
0.6615	Remote Similarity	NPC23084
0.6452	Remote Similarity	NPC6407
0.6452	Remote Similarity	NPC545184
0.631	Remote Similarity	NPC105095
0.631	Remote Similarity	NPC177731
0.631	Remote Similarity	NPC293629
0.631	Remote Similarity	NPC725
0.6296	Remote Similarity	NPC105283
0.6234	Remote Similarity	NPC5778
0.6216	Remote Similarity	NPC169248
0.6216	Remote Similarity	NPC72649
0.619	Remote Similarity	NPC44328
0.619	Remote Similarity	NPC79056
0.6145	Remote Similarity	NPC142860
0.6145	Remote Similarity	NPC152538
0.6145	Remote Similarity	NPC246469
0.6145	Remote Similarity	NPC89088
0.6133	Remote Similarity	NPC163191
0.6024	Remote Similarity	NPC271270
0.5974	Remote Similarity	NPC106625
0.5949	Remote Similarity	NPC472383
0.5897	Remote Similarity	NPC181014
0.5844	Remote Similarity	NPC471457
0.5823	Remote Similarity	NPC300537
0.5814	Remote Similarity	NPC291124
0.5814	Remote Similarity	NPC131157
0.575	Remote Similarity	NPC472381
0.575	Remote Similarity	NPC477502
0.5733	Remote Similarity	NPC99233
0.5698	Remote Similarity	NPC43587
0.5638	Remote Similarity	NPC321916
0.5606	Remote Similarity	NPC150648
0.5591	Remote Similarity	NPC318119
0.5522	Remote Similarity	NPC329203
0.5522	Remote Similarity	NPC222342
0.5507	Remote Similarity	NPC218685
0.5467	Remote Similarity	NPC604892
0.5385	Remote Similarity	NPC261254
0.5385	Remote Similarity	NPC67134
0.5375	Remote Similarity	NPC116922
0.5362	Remote Similarity	NPC18727
0.5333	Remote Similarity	NPC168789
0.5316	Remote Similarity	NPC308265
0.5316	Remote Similarity	NPC45400
0.5294	Remote Similarity	NPC274784
0.5294	Remote Similarity	NPC73028
0.5294	Remote Similarity	NPC20709
0.5294	Remote Similarity	NPC145900
0.527	Remote Similarity	NPC199335
0.5256	Remote Similarity	NPC606849
0.525	Remote Similarity	NPC486379
0.5217	Remote Similarity	NPC214454
0.52	Remote Similarity	NPC190217
0.5185	Remote Similarity	NPC149244
0.5176	Remote Similarity	NPC472382
0.5143	Remote Similarity	NPC469758
0.5132	Remote Similarity	NPC479374
0.5109	Remote Similarity	NPC47140
0.5104	Remote Similarity	NPC241196
0.5067	Remote Similarity	NPC477240
0.5067	Remote Similarity	NPC477840
0.5065	Remote Similarity	NPC121001
0.5063	Remote Similarity	NPC30432

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC553241 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4204
0.1-0.2	4780
0.2-0.3	146
0.3-0.4	15
0.4-0.5	4
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
0.619	Remote Similarity	NPD7074	Phase 3

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