NPASS Compound

Natural Product: NPC565847

Natural Product ID	NPC565847
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ilicifolinoside A
IUPAC Name	(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[(~{Z})-4-hydroxy-2-methyl-but-2-enoxy]tetrahydropyran-3,4,5-triol
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 38 38 0 0 0 0 0 0 0 0999 V2000 -3.3686 1.2281 -1.6682 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0671 0.5077 -0.3670 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9872 0.6311 0.5609 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9777 0.0601 1.8963 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9402 -0.6978 2.3108 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7970 -0.2446 -0.2720 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7770 0.6926 -0.4736 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4765 0.1452 -0.4150 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2768 0.7249 0.5765 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1147 -0.2915 1.0341 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0189 0.1727 2.1446 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8485 1.2053 1.7896 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8327 -0.8871 -0.1262 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4193 -2.2235 -0.3073 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6783 -0.1368 -1.4102 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5399 0.9530 -1.4363 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2495 0.2387 -1.7077 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6750 -0.5877 -2.6604 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4530 1.0578 -1.8781 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1562 2.3075 -1.5799 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7996 0.7345 -2.4660 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8899 1.2490 0.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9274 -0.5347 2.0864 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0284 0.9382 2.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1046 -1.6774 2.3036 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6201 -0.7401 0.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7534 -0.9615 -1.1357 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3419 -0.9575 -0.2118 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4260 -1.0584 1.4968 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3841 0.4095 3.0114 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6515 -0.6926 2.4308 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4643 1.8573 1.1657 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9387 -0.9206 0.0962 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5144 -2.6407 0.6038 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0160 -0.8310 -2.2336 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8259 1.1951 -2.3563 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1858 1.2965 -2.0492 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7688 -1.5213 -2.3474 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 1 0 2 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 10 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 15 17 1 0 17 18 1 0 17 8 1 0 1 19 1 0 1 20 1 0 1 21 1 0 3 22 1 0 4 23 1 0 4 24 1 0 5 25 1 0 6 26 1 0 6 27 1 0 8 28 1 1 10 29 1 1 11 30 1 0 11 31 1 0 12 32 1 0 13 33 1 1 14 34 1 0 15 35 1 6 16 36 1 0 17 37 1 6 18 38 1 0 M END

Standard InCHIKey	CCMAOVDWTXGECN-GMLQCYRESA-N
Standard InCHI	InChI=1S/C11H20O7/c1-6(2-3-12)5-17-11-10(16)9(15)8(14)7(4-13)18-11/h2,7-16H,3-5H2,1H3/b6-2-/t7-,8-,9+,10-,11-/m1/s1
SMILES	C/C(=C/CO)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	264.12	Volume:	249.151 ? Van der Waals volume.
Dense:	1.06	LogP:	-0.888 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.522 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.769 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	7.0
TPSA:	119.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	1.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.355	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.964	Fsp³:	0.818
MCE-18:	22.5 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.151	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.365	Promiscuous compounds:	0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.874	MDCK Permeability:	-5.081
Pgp-inhibitor:	0.0	Pgp-substrate:	0.395
PAMPA:	0.966 ? 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):	0.962
20% Bioavailability (F20%):	0.252	30% Bioavailability (F30%):	0.97
50% Bioavailability (F50%):	0.901

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.273	MRP1:	0.139
Plasma Protein Binding (PPB):	31.173%	Volume Distribution (VD):	-0.564
Fu:	71.077% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.025
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.116	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.027	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.004
HLM stability:	0.134 ? 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):

2.485

Half-life (T1/2):

2.34

ADMET: Toxicity

hERG Blockers:	0.015	hERG Blockers (10um):	0.061
Human Hepatotoxicity (H-HT):	0.636	Drug-induced Liver Injury (DILI):	0.358
AMES Toxicity:	0.897	Rat Oral Acute Toxicity:	0.019
Maximum Recommended Daily Dose:	0.006	Skin Sensitization:	0.998
Carcinogencity:	0.347	Eye Corrosion:	0.002
Eye Irritation:	0.709	Respiratory Toxicity:	0.038
Drug-induced Neurotoxicity:	0.03	Ototoxicity:	0.859
Hematotoxicity:	0.295	Drug-induced Nephrotoxicity:	0.424
Genotoxicity:	0.09	RPMI-8226 Immunitoxicity:	0.05
A549 Cytotoxicity:	0.038	Hek293 Cytotoxicity:	0.056
BCF:	0.187 ? 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:	1.779 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.117 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.47 ? 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
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15043435]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	root bark	n.a.	n.a.	PMID[17555350]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22559947]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18922	Maytenus ilicifolia	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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 NPC565847 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	22591
0.1-0.2	22664
0.2-0.3	3726
0.3-0.4	737
0.4-0.5	114
0.5-0.6	20
0.6-0.7	3
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
0.6667	Remote Similarity	NPC124963
0.6341	Remote Similarity	NPC155457
0.6053	Remote Similarity	NPC326533
0.5854	Remote Similarity	NPC233726
0.5833	Remote Similarity	NPC107914
0.5833	Remote Similarity	NPC242073
0.5682	Remote Similarity	NPC13143
0.5682	Remote Similarity	NPC294813
0.5676	Remote Similarity	NPC23134
0.549	Remote Similarity	NPC470124
0.5417	Remote Similarity	NPC147292
0.5405	Remote Similarity	NPC42503
0.5405	Remote Similarity	NPC282143
0.5405	Remote Similarity	NPC299781
0.5405	Remote Similarity	NPC157193
0.5405	Remote Similarity	NPC608193
0.5333	Remote Similarity	NPC606861
0.5333	Remote Similarity	NPC607126
0.5306	Remote Similarity	NPC63058
0.5238	Remote Similarity	NPC31496
0.5227	Remote Similarity	NPC268243
0.5111	Remote Similarity	NPC145112
0.5085	Remote Similarity	NPC488133

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC565847 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7256
0.1-0.2	1769
0.2-0.3	96
0.3-0.4	15
0.4-0.5	13
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
0.5476	Remote Similarity	NPD904	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