NPASS Compound

Natural Product: NPC539495

Natural Product ID	NPC539495
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Hexyl beta-D-galactopyranoside
IUPAC Name	(2~{R},3~{R},4~{S},5~{R},6~{R})-2-hexoxy-6-(hydroxymethyl)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 42 42 0 0 0 0 0 0 0 0999 V2000 -5.1800 1.0721 -0.8946 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4822 -0.2394 -1.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0906 -0.0750 -1.6580 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1829 0.7093 -0.7647 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9857 0.1192 0.5883 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3884 -1.2608 0.5596 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1754 -1.3710 -0.0099 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8668 -0.6838 0.4973 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2937 0.2290 -0.4699 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2251 1.1162 -0.0340 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8946 1.7007 -1.2888 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4595 0.5834 -1.9467 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3010 0.5993 0.8291 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4744 0.3300 0.0972 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9832 -0.5983 1.6435 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1956 -1.2367 1.9673 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0916 -1.5152 0.8135 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8133 -2.7009 1.4301 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8431 1.8582 -1.6078 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2915 0.9950 -1.0390 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0524 1.4054 0.1680 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5278 -0.8274 -0.1882 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0637 -0.8031 -1.8798 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1667 0.4654 -2.6232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6260 -1.0558 -1.8791 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2351 0.8773 -1.3148 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6292 1.7231 -0.6250 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3655 0.8381 1.1778 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9712 0.0968 1.0987 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1084 -1.8867 -0.0508 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3970 -1.7350 1.5622 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6113 -0.0487 1.3925 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6768 1.9764 0.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7186 2.3748 -0.9861 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1275 2.1784 -1.8998 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2275 0.8264 -2.4983 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6014 1.4216 1.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8379 -0.5491 0.2880 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4543 -0.2709 2.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2332 -1.5057 2.9043 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6547 -1.6788 -0.1470 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0205 -3.4537 0.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 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 2 22 1 0 2 23 1 0 3 24 1 0 3 25 1 0 4 26 1 0 4 27 1 0 5 28 1 0 5 29 1 0 6 30 1 0 6 31 1 0 8 32 1 1 10 33 1 1 11 34 1 0 11 35 1 0 12 36 1 0 13 37 1 1 14 38 1 0 15 39 1 1 16 40 1 0 17 41 1 6 18 42 1 0 M END

Standard InCHIKey	JVAZJLFFSJARQM-YBXAARCKSA-N
Standard InCHI	InChI=1S/C12H24O6/c1-2-3-4-5-6-17-12-11(16)10(15)9(14)8(7-13)18-12/h8-16H,2-7H2,1H3/t8-,9+,10+,11-,12-/m1/s1
SMILES	CCCCCCO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	264.16	Volume:	260.293 ? Van der Waals volume.
Dense:	1.015	LogP:	0.802 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.896 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.509 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	6.0
TPSA:	99.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	1.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.458	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.401	Fsp³:	1.0
MCE-18:	19.333 ? 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:	0.256	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.44	Promiscuous compounds:	0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.39	MDCK Permeability:	-4.802
Pgp-inhibitor:	0.001	Pgp-substrate:	0.585
PAMPA:	0.858 ? 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):	0.985
20% Bioavailability (F20%):	0.909	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.124	MRP1:	0.689
Plasma Protein Binding (PPB):	74.448%	Volume Distribution (VD):	-0.219
Fu:	26.257% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.813
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.042
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.023
CYP2C19-inhibitor:	0.026	CYP2C19-substrate:	0.029
CYP2C9-inhibitor:	0.192	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.557 ? 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):

3.303

Half-life (T1/2):

1.461

ADMET: Toxicity

hERG Blockers:	0.047	hERG Blockers (10um):	0.201
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.52
AMES Toxicity:	0.838	Rat Oral Acute Toxicity:	0.082
Maximum Recommended Daily Dose:	0.016	Skin Sensitization:	0.999
Carcinogencity:	0.376	Eye Corrosion:	0.152
Eye Irritation:	0.902	Respiratory Toxicity:	0.261
Drug-induced Neurotoxicity:	0.064	Ototoxicity:	0.773
Hematotoxicity:	0.62	Drug-induced Nephrotoxicity:	0.566
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.102
A549 Cytotoxicity:	0.834	Hek293 Cytotoxicity:	0.343
BCF:	0.95 ? 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:	3.206 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.543 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.705 ? 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
NPO53139	Rhodiola crenulata (HOOK.f.et Thoms.) H.OHBA	Genus	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7392	Malus sylvestris	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO59955	Derris trifoliata Lour.	Genus	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7392	Malus sylvestris	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 NPC539495 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	22050
0.1-0.2	22344
0.2-0.3	4541
0.3-0.4	719
0.4-0.5	160
0.5-0.6	30
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9714	High Similarity	NPC606861
0.9714	High Similarity	NPC607126
0.8571	High Similarity	NPC233726
0.675	Remote Similarity	NPC155457
0.6667	Remote Similarity	NPC124963
0.6429	Remote Similarity	NPC13143
0.6429	Remote Similarity	NPC294813
0.6304	Remote Similarity	NPC277570
0.6053	Remote Similarity	NPC326533
0.5833	Remote Similarity	NPC206601
0.5745	Remote Similarity	NPC147292
0.5714	Remote Similarity	NPC601155
0.5686	Remote Similarity	NPC488690
0.5676	Remote Similarity	NPC23134
0.56	Remote Similarity	NPC12040
0.549	Remote Similarity	NPC285003
0.5424	Remote Similarity	NPC482018
0.5424	Remote Similarity	NPC482015
0.5405	Remote Similarity	NPC42503
0.5405	Remote Similarity	NPC282143
0.5405	Remote Similarity	NPC107914
0.5405	Remote Similarity	NPC242073
0.5405	Remote Similarity	NPC299781
0.5405	Remote Similarity	NPC157193
0.5405	Remote Similarity	NPC608193
0.5227	Remote Similarity	NPC268243
0.5192	Remote Similarity	NPC280367
0.5185	Remote Similarity	NPC469469
0.5111	Remote Similarity	NPC145112
0.5102	Remote Similarity	NPC477750
0.5102	Remote Similarity	NPC477763
0.5102	Remote Similarity	NPC477757
0.5102	Remote Similarity	NPC477762
0.5102	Remote Similarity	NPC477755
0.5102	Remote Similarity	NPC477753
0.5098	Remote Similarity	NPC76881
0.5091	Remote Similarity	NPC250619
0.5088	Remote Similarity	NPC488689
0.5085	Remote Similarity	NPC603467

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC539495 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6722
0.1-0.2	2219
0.2-0.3	173
0.3-0.4	21
0.4-0.5	14
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