NPASS Compound

Natural Product: NPC227267

Natural Product ID	NPC227267
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Oxolan-2-Ylmethanol
IUPAC Name	oxolan-2-ylmethanol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2287521
PubChem CID	7360
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002648] Tetrahydrofurans

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

Standard InCHIKey	BSYVTEYKTMYBMK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C5H10O2/c6-4-5-2-1-3-7-5/h5-6H,1-4H2
SMILES	C1CC(CO)OC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	102.07	Volume:	104.06 ? Van der Waals volume.
Dense:	0.981	LogP:	-0.408 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.464 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	1.003 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	5.0
TPSA:	29.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.511	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.656	Fsp³:	1.0
MCE-18:	11.2 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.002	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? 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:	0.992	Promiscuous compounds:	0.101

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.817	MDCK Permeability:	-4.352
Pgp-inhibitor:	0.099	Pgp-substrate:	0.263
PAMPA:	0.571 ? 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):	0.143
20% Bioavailability (F20%):	0.136	30% Bioavailability (F30%):	0.148
50% Bioavailability (F50%):	0.331

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.602	MRP1:	0.686
Plasma Protein Binding (PPB):	1.441%	Volume Distribution (VD):	-0.139
Fu:	103.66% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.218
OATP1B3 inhibitor:	0.583	BCRP inhibitor:	0.105
BSEP inhibitor:	0.186

ADMET: Metabolism

CYP1A2-inhibitor:	0.147	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.173	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.775	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.719	CYP2D6-substrate:	0.024
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.004
HLM stability:	0.044 ? 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):

9.17

Half-life (T1/2):

1.217

ADMET: Toxicity

hERG Blockers:	0.085	hERG Blockers (10um):	0.277
Human Hepatotoxicity (H-HT):	0.526	Drug-induced Liver Injury (DILI):	0.271
AMES Toxicity:	0.364	Rat Oral Acute Toxicity:	0.237
Maximum Recommended Daily Dose:	0.033	Skin Sensitization:	0.642
Carcinogencity:	0.639	Eye Corrosion:	0.985
Eye Irritation:	0.998	Respiratory Toxicity:	0.443
Drug-induced Neurotoxicity:	0.442	Ototoxicity:	0.604
Hematotoxicity:	0.252	Drug-induced Nephrotoxicity:	0.405
Genotoxicity:	0.005	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.032	Hek293 Cytotoxicity:	0.021
BCF:	0.289 ? 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:	1.441 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	1.898 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.255 ? 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
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	Flowers	Tantempango, Hidalgo, Mexico	2019-May	DOI[10.1007/s11130-020-00822-2]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16297615]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[18543151]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24358188]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8778246]
NPO2837	Aloe spicata	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14763	Aloe ferox	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2997	Aloe africana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14763	Aloe ferox	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14763	Aloe ferox	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14763	Aloe ferox	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2997	Aloe africana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2837	Aloe spicata	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14763	Aloe ferox	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11578	Aloe vera	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2997	Aloe africana	Species	Xanthorrhoeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14763	Aloe ferox	Species	Asphodelaceae	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
Potency	7

Activity Type	# Activity
Others	7

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
NPT2	Others	Unspecified	n.a.	Potency	n.a.	54947.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	55957.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	78369.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	27539.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	24995.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	48972.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	27806.6	nM	PubChem BioAssay data set

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
-	Rattus norvegicus	NOAEL	=	50.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	150.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	40.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	1000.0	ppm	ToxVal
-	Rattus norvegicus	NOAEC	<	208.862	mg/m3	ToxVal
-	Rattus norvegicus	LOAEL	=	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	500.0	ppm	ToxVal
-	Rattus norvegicus	NOAEC	=	208.862	mg/m3	ToxVal
-	Rattus norvegicus	NOAEL	=	100.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	~	96.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	78.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	39.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LOAEC	=	208.862	mg/m3	ToxVal
-	Rattus norvegicus	NOAEL	=	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LD50	>	2000.0	mg/kg	ToxVal
-	Rattus norvegicus	LC50	>	3137.11	mg/m3	ToxVal
-	Rattus norvegicus	LD50	=	1600.0	mg/kg	ToxVal
-	Rattus norvegicus	NOEL	=	40.0	mg/kg-day	ToxVal
-	Mus musculus	NOAEL	=	60.0	mg/kg-day	ToxVal
-	Mus musculus	LOAEL	=	159.0	mg/kg-day	ToxVal
-	Mus musculus	NOAEL	=	760.0	mg/kg-day	ToxVal
-	Mus musculus	LD50	=	2300.0	mg/kg	ToxVal
-	Homo sapiens	DNEL systemic	=	1.4	mg/m3	ToxVal
-	Cavia porcellus	LD50	=	5000.0	mg/kg	ToxVal
-	Cavia porcellus	LD50	=	800.0	mg/kg	ToxVal
-	Canis lupus familiaris	NOAEL	<	37.0	mg/kg-day	ToxVal

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 NPC227267 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	30334
0.1-0.2	18954
0.2-0.3	536
0.3-0.4	32
0.4-0.5	2
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	Natural Product ID
		NPC

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC227267 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7183
0.1-0.2	1868
0.2-0.3	92
0.3-0.4	7
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