NPASS Compound

Natural Product: NPC476549

Natural Product ID	NPC476549
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl(butylthio) sulfoxide
IUPAC Name	1-methylsulfinylsulfanylbutane
Synonyms	S-N-Butyl Methanethiosulfinate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11073618
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001161] Thiosulfinic acid esters

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	CNIVRPRPTZFKJH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C5H12OS2/c1-3-4-5-7-8(2)6/h3-5H2,1-2H3
SMILES	CCCCSS(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	152.03	Volume:	140.845 ? Van der Waals volume.
Dense:	1.079	LogP:	0.461 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.608 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.002 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	0.0
TPSA:	23.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.348	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.681	Fsp³:	1.0
MCE-18:	1.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.008	Fluc inhibitor:	0.291 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? 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:	0.904	Promiscuous compounds:	0.705

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.589	MDCK Permeability:	-4.535
Pgp-inhibitor:	0.635	Pgp-substrate:	0.0
PAMPA:	0.142 ? 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):	0.397
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.266
50% Bioavailability (F50%):	0.07

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.544	MRP1:	0.811
Plasma Protein Binding (PPB):	40.961%	Volume Distribution (VD):	0.09
Fu:	58.072% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.008
BSEP inhibitor:	0.982

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.86	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.347	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.697	CYP3A4-substrate:	0.731
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.257
HLM stability:	0.996 ? 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):

10.071

Half-life (T1/2):

1.002

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.138
Human Hepatotoxicity (H-HT):	0.087	Drug-induced Liver Injury (DILI):	0.988
AMES Toxicity:	0.438	Rat Oral Acute Toxicity:	0.674
Maximum Recommended Daily Dose:	0.763	Skin Sensitization:	1.0
Carcinogencity:	0.558	Eye Corrosion:	1.0
Eye Irritation:	1.0	Respiratory Toxicity:	0.998
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.001
Hematotoxicity:	0.007	Drug-induced Nephrotoxicity:	0.008
Genotoxicity:	0.843	RPMI-8226 Immunitoxicity:	0.01
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.078
BCF:	1.66 ? 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:	3.61 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.826 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.332 ? 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
NPO8374	Allium siculum	Species	Amaryllidaceae	Eukaryota	bulb	n.a.	n.a.	PMID[12141853]
NPO8374	Allium siculum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8374	Allium siculum	Species	Amaryllidaceae	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
IZ	21

Activity Type	# Activity
Organism	21

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
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	0	mm	PMID[12141853]
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	16	mm	PMID[12141853]
NPT2710	Organism	Streptococcus agalactiae	Streptococcus agalactiae	IZ	=	24	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	0	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	20	mm	PMID[12141853]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	26	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	0	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	14	mm	PMID[12141853]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	20	mm	PMID[12141853]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	IZ	=	0	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	0	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	12	mm	PMID[12141853]
NPT1521	Organism	Stenotrophomonas maltophilia	Stenotrophomonas maltophilia	IZ	=	17	mm	PMID[12141853]
NPT2923	Organism	Klebsiella pneumoniae subsp. pneumoniae	Klebsiella pneumoniae subsp. pneumoniae	IZ	=	0	mm	PMID[12141853]
NPT2923	Organism	Klebsiella pneumoniae subsp. pneumoniae	Klebsiella pneumoniae subsp. pneumoniae	IZ	=	12	mm	PMID[12141853]
NPT2923	Organism	Klebsiella pneumoniae subsp. pneumoniae	Klebsiella pneumoniae subsp. pneumoniae	IZ	=	20	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	0	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	22	mm	PMID[12141853]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	28	mm	PMID[12141853]

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 NPC476549 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	28810
0.1-0.2	19864
0.2-0.3	1009
0.3-0.4	113
0.4-0.5	30
0.5-0.6	11
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC3693
0.7895	Intermediate Similarity	NPC248233
0.75	Intermediate Similarity	NPC40965
0.7368	Intermediate Similarity	NPC140229
0.7143	Intermediate Similarity	NPC86545
0.7143	Intermediate Similarity	NPC286498
0.7143	Intermediate Similarity	NPC223374
0.7143	Intermediate Similarity	NPC196442
0.7143	Intermediate Similarity	NPC301398
0.7143	Intermediate Similarity	NPC608162
0.7143	Intermediate Similarity	NPC609004
0.7	Intermediate Similarity	NPC166804
0.6111	Remote Similarity	NPC110107
0.6087	Remote Similarity	NPC35371
0.6087	Remote Similarity	NPC476550
0.6	Remote Similarity	NPC281943
0.5652	Remote Similarity	NPC226511
0.56	Remote Similarity	NPC603612
0.5417	Remote Similarity	NPC322892
0.5417	Remote Similarity	NPC12904
0.5294	Remote Similarity	NPC23508
0.5263	Remote Similarity	NPC327450
0.5263	Remote Similarity	NPC234005
0.5238	Remote Similarity	NPC8368
0.52	Remote Similarity	NPC154396
0.52	Remote Similarity	NPC286695
0.52	Remote Similarity	NPC155872

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476549 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6682
0.1-0.2	2327
0.2-0.3	118
0.3-0.4	16
0.4-0.5	4
0.5-0.6	1
0.6-0.7	1
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
0.6667	Remote Similarity	NPD900	Pre-clinical
0.5385	Remote Similarity	NPD9378	Phase 4

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