NPASS Compound

Natural Product: NPC506656

Natural Product ID	NPC506656
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{R},4~{S},5~{S},6~{R})-2-(3-ethyl-4-hydroxy-4-methyl-pentoxy)-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
IUPAC Name	(2~{R},3~{R},4~{S},5~{S},6~{R})-2-(3-ethyl-4-hydroxy-4-methyl-pentoxy)-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 49 49 0 0 0 0 0 0 0 0999 V2000 -3.0480 -1.3679 -1.9808 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1459 -0.3345 -1.3473 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5939 -0.0391 0.0259 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7770 0.9716 0.7788 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3461 0.6324 0.9830 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3921 0.4619 -0.1836 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6839 0.1552 0.1749 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6321 1.0327 -0.3370 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8321 0.7683 0.3172 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8862 1.8128 -0.0125 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0401 1.4637 0.6837 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3641 -0.6114 0.0203 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5123 -0.7768 0.8098 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3187 -1.6275 0.4072 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6901 -2.9194 0.0592 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0390 -1.2263 -0.3366 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0297 -2.1441 -0.1403 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0616 0.3531 0.0022 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5262 0.6739 1.4361 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3499 1.5460 -0.8439 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8905 -0.6885 -0.4024 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4815 -1.9391 -2.7855 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3708 -2.1674 -1.2839 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9348 -0.9460 -2.4755 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2277 0.5773 -2.0026 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1191 -0.7431 -1.4290 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5484 -0.9866 0.6234 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8092 1.9845 0.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2271 1.1413 1.7782 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1771 -0.1915 1.7085 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1176 1.5339 1.4857 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8294 0.1170 1.2836 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6262 0.8764 1.4100 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5643 2.8050 0.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1382 1.8202 -1.0938 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0751 1.9148 1.5799 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5752 -0.7033 -1.0450 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6705 -1.7261 0.9773 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1422 -1.5286 1.4963 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9282 -3.5089 0.2801 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3438 -1.1229 -1.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2044 -2.9116 -0.7606 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6349 0.5275 1.5182 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9937 0.0553 2.1726 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3445 1.7385 1.6482 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0905 2.2406 -0.3989 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3995 2.0857 -1.1178 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7693 1.2002 -1.8101 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7683 -0.2791 -0.6129 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 9 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 3 18 1 0 18 19 1 0 18 20 1 0 18 21 1 0 16 7 1 0 1 22 1 0 1 23 1 0 1 24 1 0 2 25 1 0 2 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 0 5 31 1 0 7 32 1 1 9 33 1 1 10 34 1 0 10 35 1 0 11 36 1 0 12 37 1 6 13 38 1 0 14 39 1 1 15 40 1 0 16 41 1 6 17 42 1 0 19 43 1 0 19 44 1 0 19 45 1 0 20 46 1 0 20 47 1 0 20 48 1 0 21 49 1 0 M END

Standard InCHIKey	RPOFRRIWKBGKCV-ZVACVBPESA-N
Standard InCHI	InChI=1S/C14H28O7/c1-4-8(14(2,3)19)5-6-20-13-12(18)11(17)10(16)9(7-15)21-13/h8-13,15-19H,4-7H2,1-3H3/t8?,9-,10-,11+,12-,13-/m1/s1
SMILES	CCC(CCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C(C)(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	308.18	Volume:	303.675 ? Van der Waals volume.
Dense:	1.015	LogP:	-0.277 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.202 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.237 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	6.0
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:	0.409	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.124	Fsp³:	1.0
MCE-18:	28.286 ? 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:	0.169	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.314	Promiscuous compounds:	0.074

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.284	MDCK Permeability:	-4.857
Pgp-inhibitor:	0.001	Pgp-substrate:	0.633
PAMPA:	0.729 ? 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):	0.189
20% Bioavailability (F20%):	0.005	30% Bioavailability (F30%):	0.303
50% Bioavailability (F50%):	0.405

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.744	MRP1:	0.238
Plasma Protein Binding (PPB):	38.289%	Volume Distribution (VD):	-0.525
Fu:	63.337% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.865
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.195
BSEP inhibitor:	0.008

ADMET: Metabolism

CYP1A2-inhibitor:	0.989	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.581	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.319	CYP2D6-substrate:	0.011
CYP3A4-inhibitor:	0.09	CYP3A4-substrate:	0.462
CYP2B6-substrate:	0.008	CYP2C8-inhibitor:	0.555
HLM stability:	0.981 ? 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):

4.364

Half-life (T1/2):

1.939

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.603	Drug-induced Liver Injury (DILI):	0.203
AMES Toxicity:	0.712	Rat Oral Acute Toxicity:	0.017
Maximum Recommended Daily Dose:	0.009	Skin Sensitization:	0.995
Carcinogencity:	0.416	Eye Corrosion:	0.003
Eye Irritation:	0.366	Respiratory Toxicity:	0.025
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.941
Hematotoxicity:	0.421	Drug-induced Nephrotoxicity:	0.611
Genotoxicity:	0.01	RPMI-8226 Immunitoxicity:	0.076
A549 Cytotoxicity:	0.084	Hek293 Cytotoxicity:	0.103
BCF:	0.31 ? 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:	2.506 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.082 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.066 ? 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
NPO64407	Eucalyptus notabilis	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC506656 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	19741
0.1-0.2	25270
0.2-0.3	3981
0.3-0.4	719
0.4-0.5	124
0.5-0.6	14
0.6-0.7	7
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
0.675	Remote Similarity	NPC233726
0.6429	Remote Similarity	NPC155457
0.6316	Remote Similarity	NPC124963
0.6136	Remote Similarity	NPC13143
0.6136	Remote Similarity	NPC294813
0.6136	Remote Similarity	NPC606861
0.6136	Remote Similarity	NPC607126
0.575	Remote Similarity	NPC326533
0.5714	Remote Similarity	NPC277570
0.5625	Remote Similarity	NPC166250
0.5526	Remote Similarity	NPC107914
0.5526	Remote Similarity	NPC242073
0.551	Remote Similarity	NPC147292
0.5385	Remote Similarity	NPC23134
0.5283	Remote Similarity	NPC280367
0.5128	Remote Similarity	NPC42503
0.5128	Remote Similarity	NPC282143
0.5128	Remote Similarity	NPC299781
0.5128	Remote Similarity	NPC157193
0.5128	Remote Similarity	NPC608193
0.5094	Remote Similarity	NPC471879

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC506656 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6443
0.1-0.2	2547
0.2-0.3	133
0.3-0.4	14
0.4-0.5	12
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
0.5227	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