NPASS Compound

Natural Product: NPC238243

Natural Product ID	NPC238243
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lysidiside E
IUPAC Name	(2S,3R,4R,5R,6S)-2-[(2S,3R,4S,5R)-4,5-dihydroxy-2-[3-hydroxy-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenoxy]oxan-3-yl]oxy-6-methyloxane-3,4,5-triol
Synonyms	Lysidiside E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL575437
PubChem CID	45481961
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes [CHEMONTID:0000142] Stilbene glycosides

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 66 69 0 0 0 0 0 0 0 0999 V2000 3.1206 -3.7425 -1.2543 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3888 -2.5618 -1.2981 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9977 -2.5471 -1.1246 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2600 -1.4041 -1.1631 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9693 -0.2159 -1.3892 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3486 -0.1879 -1.5665 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0531 -1.3554 -1.5209 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0072 1.1136 -1.8077 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2894 1.2452 -1.9828 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9557 2.5207 -2.2222 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2839 3.7140 -2.2924 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9707 4.9127 -2.5279 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3347 4.9557 -2.6977 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0174 3.7395 -2.6253 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3337 2.5722 -2.3944 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0297 6.1356 -2.9315 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0900 -1.3368 -1.0017 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9264 -2.4129 -0.7677 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8156 -2.5394 -1.8478 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9354 -3.2653 -1.5082 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6630 -4.2989 -0.4664 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3150 -3.5847 0.8287 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7324 -2.1977 0.5273 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8413 -1.7702 1.4700 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1121 -0.5149 1.9874 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1292 0.3793 1.6679 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4900 1.7041 1.7689 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0725 2.1190 0.4198 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4885 1.8878 2.8780 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1328 0.8833 3.9735 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4199 -0.5312 3.4544 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7378 -0.7959 3.7156 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8760 1.1619 5.1054 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5332 3.1744 3.3602 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5323 -3.3499 1.4806 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6952 -5.2188 -0.8467 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2313 -4.2231 -2.1616 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5215 -3.5045 -0.9576 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4246 0.6979 -1.4264 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1263 -1.3511 -1.6563 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4072 2.0195 -1.8436 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9349 0.3803 -1.9565 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2085 3.7861 -2.1724 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4251 5.8452 -2.5812 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0836 3.7831 -2.7603 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9160 1.6467 -2.3458 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4865 6.6867 -2.2461 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3401 -3.3378 -0.6405 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4338 -3.6911 -2.4086 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6607 -2.5376 -1.0614 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6049 -4.8737 -0.3127 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6258 -4.1830 1.4517 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5361 -1.4986 0.2872 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0517 -0.1679 1.4621 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6275 2.3645 1.9956 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9145 1.4620 0.1234 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4515 3.1663 0.4366 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2951 1.9778 -0.3563 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4883 1.5945 2.4697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0673 1.0251 4.2113 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7884 -1.2768 3.9811 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8894 -1.6119 4.2732 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1365 2.1117 5.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3226 3.6526 3.0093 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0241 -2.6048 1.0962 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3295 -5.7258 -0.1063 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 13 16 1 0 4 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 29 34 1 0 22 35 1 0 21 36 1 0 7 2 1 0 15 10 1 0 23 18 1 0 31 25 1 0 1 37 1 0 3 38 1 0 5 39 1 0 7 40 1 0 8 41 1 0 9 42 1 0 11 43 1 0 12 44 1 0 14 45 1 0 15 46 1 0 16 47 1 0 18 48 1 1 20 49 1 0 20 50 1 0 21 51 1 1 22 52 1 1 23 53 1 6 25 54 1 6 27 55 1 1 28 56 1 0 28 57 1 0 28 58 1 0 29 59 1 6 30 60 1 1 31 61 1 1 32 62 1 0 33 63 1 0 34 64 1 0 35 65 1 0 36 66 1 0 M END

Standard InCHIKey	HMYSHADLMCHJFF-VYXPBXMQSA-N
Standard InCHI	InChI=1S/C25H30O11/c1-12-19(29)21(31)22(32)24(34-12)36-23-20(30)18(28)11-33-25(23)35-17-9-14(8-16(27)10-17)3-2-13-4-6-15(26)7-5-13/h2-10,12,18-32H,11H2,1H3/b3-2+/t12-,18+,19-,20-,21+,22+,23+,24-,25-/m0/s1
SMILES	Oc1cc(cc(c1)/C=C/c1ccc(cc1)O)O[C@@H]1OC[C@H]([C@@H]([C@H]1O[C@@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.18	Volume:	484.968 ? Van der Waals volume.
Dense:	1.044	LogP:	1.911 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.193 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.132 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	178.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.261	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.461	Fsp³:	0.44
MCE-18:	92.444 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.634	Fluc inhibitor:	0.998 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.218 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.297 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.385	Promiscuous compounds:	0.278

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.12	MDCK Permeability:	-5.172
Pgp-inhibitor:	0.0	Pgp-substrate:	0.152
PAMPA:	0.998 ? 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%):	0.882	30% Bioavailability (F30%):	0.992
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.014
Plasma Protein Binding (PPB):	77.445%	Volume Distribution (VD):	-0.323
Fu:	24.024% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.049
BSEP inhibitor:	0.003

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.055
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.094
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.05 ? 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):

2.039

Half-life (T1/2):

4.567

ADMET: Toxicity

hERG Blockers:	0.076	hERG Blockers (10um):	0.271
Human Hepatotoxicity (H-HT):	0.818	Drug-induced Liver Injury (DILI):	0.689
AMES Toxicity:	0.848	Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.056	Skin Sensitization:	0.998
Carcinogencity:	0.049	Eye Corrosion:	0.0
Eye Irritation:	0.664	Respiratory Toxicity:	0.01
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.932
Hematotoxicity:	0.066	Drug-induced Nephrotoxicity:	0.919
Genotoxicity:	0.752	RPMI-8226 Immunitoxicity:	0.204
A549 Cytotoxicity:	0.452	Hek293 Cytotoxicity:	0.571
BCF:	0.682 ? 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:	3.3 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.844 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.948 ? 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
NPO33047	lysidice brevicalyx wei	Species	n.a.	Eukaryota	Barks	n.a.	n.a.	PMID[18847246]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27203291]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28310	Phacelocarpus labillardieri	Species	Phacelocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28129	Reticulitermes virginicus	Species	Termitoidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23676	Fleroya rubrostipulata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28114	Peltophorum adnatum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23882	Cremastosperma microcarpum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27974	Swertia leduci	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28310	Phacelocarpus labillardieri	Species	Phacelocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28982	Calliandra confusa	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

Activity Type	# Activity
Activity	2

Activity Type	# Activity
Non-molecular	2

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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	67.0	%	PMID[18847246]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	6.0	%	PMID[18847246]

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 NPC238243 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	16058
0.1-0.2	29024
0.2-0.3	4265
0.3-0.4	468
0.4-0.5	27
0.5-0.6	6
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8529	High Similarity	NPC188555
0.7808	Intermediate Similarity	NPC89686
0.7808	Intermediate Similarity	NPC257095
0.7746	Intermediate Similarity	NPC138350
0.7746	Intermediate Similarity	NPC165482
0.6892	Remote Similarity	NPC40664
0.6892	Remote Similarity	NPC197723
0.6329	Remote Similarity	NPC273932
0.6316	Remote Similarity	NPC130496
0.5833	Remote Similarity	NPC85799
0.5833	Remote Similarity	NPC303422
0.5432	Remote Similarity	NPC3293
0.5065	Remote Similarity	NPC242028
0.5065	Remote Similarity	NPC203230
0.5059	Remote Similarity	NPC289346

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC238243 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4392
0.1-0.2	4661
0.2-0.3	95
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
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
		NPD

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